How to Use This Guide & Important Phone Numbers
Microbiology Overview
Antimicrobial Fundamental Concepts
Antibiotic Overview
Antifungals
Clostridium difficile Infection
Central Nervous System Infections
Specific Treatment of Select Bacterial Organisms at UCLA
Bloodstream Infections
Pulmonary Infections
Sepsis
Skin/Soft Tissue Infections
Urinary Tract Infections
Penicillin Allergy
Endocarditis Prophylaxis
Antibiotic resistance has increased dramatically over the past several decades. Increasing resistance, coupled with a pipeline for new antimicrobial agents which has all but dried up, has meant prudent use of antibiotics is critically important. The selection of optimal therapy for infections can be a daunting task for healthcare professionals. Antibiotic resistance is among the most serious issues facing contemporary healthcare. Changing antibiotic resistance patterns, rising antibiotic costs and the introduction of new antibiotics have made selecting optimal antibiotic regimens more difficult now than ever before. Antibiotics are the only class of medications where use in one patient can directly impact another patient. As a response to these challenges, the UCLA Antimicrobial Stewardship Program was created in July 2010. Directed by an Infectious Diseases physician (Daniel Z. Uslan, M.D.) and Infectious Disease pharmacist (Meganne Kanatani, Pharm.D.), the intent of the program is to optimize antimicrobial use at UCLA through appropriate selection, dosing, and duration of therapy. Our goals are to improve clinical outcomes by ensuring patients with infection are appropriately treated, reducing the emergence of resistance, limiting drug-related adverse events, and minimizing the risk of unintentional consequences associated with antimicrobials, such as C. diff. These guidelines are a step in that direction.
These guidelines are based on current literature reviews, including national guidelines and consensus statements, current microbiology data from the UCLA lab, and UCLA faculty expert opinion. Faculty from various departments have reviewed and approved these guidelines. As you will see, in addition to antibiotic recommendations, the guidelines also contain information about diagnosis, test ordering, and other useful management tips.
As the name implies, these are only guidelines, and can never substitute for clinical judgement. This book is not intended to serve as a comprehensive resource for treatment of infections, and expert consultation is always s uggested for complex infections. If you have specific feedback on sections or are interested in more information on any of the topics herein, please feel free to contact us. Our goal is for the Antimicrobial Stewardship Program to serve as a valued service in optimizing the care of the 60% of UCLA patients who receive antimicrobials. We welcome your thoughts and comments to: (310) 267-7567 or to ASP@ucla.edu.
Thank you,
Daniel Z. Uslan, M.D., M.S. Director, Antimicrobial Stewardship Program
Meganne Kanatani, Pharm.D. Infectious Diseases Pharmacist
How to use this guide
- Each section begins by giving recommendations for the choice and dose of antibiotics for the particular infection.
- ALL DOSES IN THE TEXT ARE FOR ADULTS WITH NORMAL RENAL AND HEPATIC FUNCTION.
- If your patient does NOT have normal renal or hepatic function, please refer to the sections on antibiotic dosing to determine the correct dose, or ask your friendly neighborhood pharmacist.
- Following the antibiotic recommendations, we have tried to include some important treatment notes that explain a bit about WHY the particular antibiotics were chosen and that provide some important tips on diagnosis and management. PLEASE glance at these notes when you are treating infections, as we think the information will prove helpful.
The recommendations given in this guide are meant to serve as treatment guidelines. They should NOT supplant clinical judgment or Infectious Diseases consultation. The recommendations were developed for use at UCLA Health System hospitals are may not be appropriate for other settings. We have attempted to verify that all information is correct, but research changes. If there is any doubt, please verify the information in this guide by calling the antimicrobial stewardship program at (310) 267-7567 or obtaining Infectious Diseases consultation.
Important Phone Numbers
Antibiotic approval: 7-7567
• Please note that text pages alone are NOT sufficient and MUST include a call-back phone and pager number.
• ALL orders for restricted antibiotics MUST be approved unless they are part of a pre-printed order set.
• Antibiotic Management Program: 7-7567
• Penicillin Allergy Skin Test nurse: 5-4369
• Infectious Diseases Consults:
RRUMC pager: 98771
SMH page: 96002
Transplant ID: 93424
• Antimicrobial lab (AML): 4-2760, Micro Fellow page number: 90103
Bacteriology
Blood cultures………………………………….42757
General cultures……………………………….42758
AML, Anaerobes……………………………….42760
Virology…………………………………………………….42767
Mycobacteriology, Mycology and Parasitology………..42770
Immunoserology…………………………………………..42745 / 42776
Specimen processing……………………………………..42748 / 42749
Microbiology Overview Interpretation of preliminary microbiology data
| Gram-positive cocci | Gram-negative cocci |
| Aerobic In clusters ● Coagulase (+): Staphylococcus aureus ● Coagulase (-): Staphylococcus lugdunensis and other coagulase-negative staphylococci In pairs/chains ● Optochin sensitive: Streptococcus pneumoniae ● Alpha-hemolytic: Viridans group Streptococcus, Enterococcus ● Beta-hemolytic: ○ Group A Strep (Streptococcus pyogenes) ○ Group B Strep (Streptococcus agalactiae) ○ Group C, D, G Strep Anaerobic: Peptostreptococcus spp. and many others |
Aerobic
● Diplococcus: Neisseria meningitidis, N. gonorrhoeae, Moraxella catarrhalis
● Cocco-bacillus: Haemophilus influenzae, Acinetobacter
Anaerobic: Veillonella spp.
Gram-positive rods
Gram-negative rods
Aerobic
● Large: Bacillus spp
● Cocco-bacillus: Listeria monocytogenes, Lactobacillus spp
● Small, pleomorphic: Corynebacterium spp
● Branching filaments: Nocardia spp, Streptomyces spp
Anaerobic
● Large: Clostridium spp
● Small, pleomorphic: P. acnes, Actinomyces spp
Aerobic
Lactose fermenting (Lactose positive):
● Enterobacter spp, Escherichia coli, Klebsiella spp
● Citrobacter spp*, Serratia spp*
Non lactose-fermenting (Lactose negative):
● Oxidase (-): Acinetobacter spp, Burkholderia spp, E. coli, Proteus spp, Salmonella spp, Shigella spp, Serratia spp*, Stenotrophomonas maltophilia
● Oxidase (+): P. aeruginosa, Aeromonas spp.
Anaerobic: Bacteroides spp, Fusobacterium spp, Prevotella spp.
*Serratia and Citrobacter spp can appear initially as non-lactose fermenting due to slow fermentation.
Interpretations of Key Phrases
● “Gram positive cocci in clusters” may suggest Staphyloccocus species.
● "Gram positive cocci in pairs and chains" may suggest Streptococcus species or Enterococcus species.
● “Gram negative coccobacilli” may suggest Haemophilus species.
● “Lactose-positive gram negative rods” may suggest Enterobacteriaceae, such as E. coli, Klebsiella, or Enterobacter spp.
● “Lactose-negative gram negative rods” may suggest Pseudomonas.
● “Branching Gram positive rods, modified acid fast stain positive” may suggest Nocardia or Streptomyces species.
● “Acid fast bacilli” may suggest Mycobacterium species.
● “Yeast” suggests Candida spp. "Germ-tube negative yeast" suggests non-albicans Candida yeast. “Germ-tube positive yeast” is identified as Candida albicans or Candida dubliniensis.
● “Round Yeast” suggests Cryptococcus spp.
● “Fungal elements or hyphal elements” suggest filamentous fungi (moulds).
Quantitation values (rare/few/moderate/many) are reported on some cultures, and indicate the number of a specific bacterium present in the culture. The interpretation of these valuesdepend on a number of factors including: source of the culture, Gram stain results, organism, likelihood that the culture was contaminated based on the organisms that are isolated, number of organisms that grow, and patient gender. When a report says “rare gram-negative rod,” it does not mean an unusual bacterium, but that it was present in low numbers.
Susceptibility Testing
The UCLA microbiology laboratory utilizes standard reference methods for determining susceptibility. Urine isolates are tested by an automated system.
The minimal inhibitory concentration (MIC) represents the concentration of the antimicrobial agent that inhibits the growth of the organism in vitro.
The MIC of each antibiotic tested against the organism is reported with one of four interpretations: S (susceptible), I (intermediate), R (resistant) or NS (non-susceptible). These interpretations are based on the serum achievable concentration of antibiotic, clinical outcome data, and MIC distributions of wild-type bacteria.
The “susceptible” category implies the isolate is inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat the site of infection is used.
The “resistant” category implies the isolate is not inhibited by these usually achievable concentrations, OR that the organisms might express a resistance mechanism.
The “intermediate” category indicates that the MIC is approaching the usually attainable concentration, but that response rates may be lower than for a susceptible isolate. Clinical efficacy can potentially be expected in body sites where the drug is concentrated (e.g. aminoglycosides and beta-lactams in the urine) or when a higher dose of the drug can be used (e.g. beta-lactams).
Finally, the “non-susceptible” category is reserved for isolates that only have had “S” criteria assigned, but that have an MIC isolate about this “S” value. A “NS” value does not necessarily mean that the isolate has a resistance mechanism, but rather that it has an unusually high MIC.
MICs which are ½ to ⅛ the breakpoint MIC are more frequently utilized to treat infections where antibiotic penetration is variable or poor (endocarditis, meningitis, osteomyelitis, pneumonia). Similarly, some organisms yielding antibiotic MICs at the breakpoint frequently possess or have acquired a low-level resistance determinant with the potential for selection of high-level expression and resistance. This is the most notable with cephalosporins and Enterobacter, Serratia, Morganella, Providencia, Citrobacter, and Pseudomonas spp. These organisms all possess a chromosomal beta-lactamase which frequently will be overexpressed during therapy despite initial in vitro susceptibility.
MIC values are interpreted using the Clinical Laboratory Standards Institute (CLSI) breakpoints, which are published yearly. These interpretive standards are based on many factors, including clinical, pharmacokinetic, pharmacodynamic, and microbiological studies. It is important to be aware that although there are many examples of bacteria and antibiotics for which we have CLSI breakpoints (particularly for the most common pathogens), there are some bacteria and antibiotics for which there are no breakpoints. Consultation with the Microbiology Laboratory or Infectious Diseases is strongly encouraged when seeking and interpreting MIC data in these circumstances. On the microbiology report, these results are interpreted with the % sign, indicating that no breakpoint exists for that drug/bug combination. The % sign does not mean that a certain % are susceptible or resistant.
NOTE: MIC values vary from one drug to another and from one bacterium to another, and thus the MIC values are NOT comparable between antibiotics or between organisms. Do not be tempted to select an antibiotic solely because the MIC is lower than other options.
Selection of Antimicrobial Agents for Testing/Reporting
The laboratory chooses agents to routinely test and report based on:
● Clinical appropriateness for treating infections caused by the species.
● Known inherent resistance of some bacteria to some agents.
● Body site from which the organism was isolated.
● Overall antimicrobial susceptibility profile.
● Agents available on the UCLA formulary.
● Selective reporting, where results of broad spectrum agents are withheld if narrow spectrum agents within a given class are active.
● Cost and toxicity issues.
The laboratory only reports results on antimicrobial agents that are documented to be clinically appropriate for the species tested.
Bacteriology Contaminant vs Pathogen
| Source | Pathogens | Likely Contaminants / Normal Flora |
| Blood - normally sterile Note: The number of cultures drawn versus the number of positive bottles, and the patient’s clinical syndrome must be considered when evaluating blood culture results. Multiple positive bottle drawn from a single venipuncture or sequentially through one line are not considered separately when evaluating the potential significance of a likely contaminant | Any organism isolated | ● Coagulase-negative staphylococci ● Alpha-hemolytic (viridans) streptococci ● Bacillus spp. ● Corynebacterium spp. (Except C. jeikeium) ● Propionibacteirum acnes ● Micrococcus |
| Tissue and body fluids - normally sterile | Any organism isolated; use judgment to evaluate the possibility of normal flora being present in relation to the source of the specimen. | Eye/Ear ● Coagulase-negative staphylococci ● Non-hemolytic streptococci ● Alpha-hemolytic streptococci ● Corynebacterium Skin ● Coagulase-negative staphylococci ● P. acnes ● Corynebacterium ● Alpha-hemolytic streptococci ● Bacillus spp. |
| Genital | Neisseria gonorrhoeae Beta-hemolytic streptococci (in pregnancy) Listeria monocytogenes Predominant numbers of: Gardnerella vaginalis (in women) S. aureus yeast | Staphylococcus spp Lactobacillus spp Corynebacterium Enterococcus spp Streptococcus spp Gram-negative rods Anaerobes Yeast |
| Urine - normally sterile. Significance of organism is determined by colony count. Urine from stomas/conduits is not sterile | Enterobacteriaceae Enterococcus spp Pseudomonas spp Group B streptococci (in pregnancy) S. aureus S. saprophyticus Yeast | Significance determined by colony count Corynebacterium Coagulase-negative staphylcocci Alpha-hemolytic streptococci Lactobacillus spp Gram-negative rods Bacillus spp |
| Gastrointestinal Tract | Salmonella spp Shigella spp Campylobacter jejuni Aeromonas/Plesiomonas Yersinia enterocolitica Vibrio spp S. aureus (in the context of food poisoning) | Enterobacteriaceae Staphylococcus spp Streptococcus spp Enterococcus spp Pseudomonas spp Anaerobes Yeast |
| Respiratory Tract Amount of organism present, source of culture, presence of endotracheal tube or tracheostomy, immune status, and patient age may determine significance as a pathogen. | Group A streptococci Streptococcus pneumoniae* S. aureus (predominant) H. influenzae* Neisseria meningitidis Enterobacteriaceae (predominant) Pseudomonas (predominant) Nocardia spp Moraxella catarrhalis* (predominant) | Staphylcoccus spp Alpha-hemolytic streptococci Gram-negative rods Beta-hemolytic streptococci other than Group A Saprophytic Neisseria spp Enterococcus spp Corynebacterium spp Bacillus spp Yeast Anaerobes Haemophilus spp Micrococcus spp Stomatococcus spp (Rothia) |
Specific Cultures Stool cultures
Stool culture for bacterial pathogens:
● If a stool culture is ordered, the laboratory will screen for Salmonella, Shigella spp, Plesiomonas shigelloides, and Aeromonas spp.
● The most commonly isolated bacterial pathogen causing bacterial gastroenteritis at UCLA is Campylobacter jejuni. A dedicated EIA should be ordered.
● If Yersinia enterocolitica or Vibrio sp are suspected, alert the laboratory as specialized media are required to optimize recovery of these organisms.
● A total of three specimens received on separate days will increase the probability of isolating the etiologic agent in greater than 95% of the cases.
● It is inappropriate to order a stool culture on patients who develop diarrhea after >3 days in the hospital; in these situations, studies have shown that the most common pathogen is C. difficile, and the C. difficile nucelic acid amplification test (NAAT) should be ordered.
Clostridium difficile DNA assay
● The C. difficile testing is performed by nucleic acid amplification test (NAAT) at UCLA.
● This test is >99% sensitive and specific, therefore empiric therapy for patients with negative C. difficile NAAT should be avoided.
● Due to the high sensitivity and specificity, repeat testing is unnecessary.
● This test is not indicated for test of cure, as patients may remain positive for 30 days following clinical cure. Many patients will continue to carry the organism without any clinical manifestations of colitis and need no further treatment.
● Only one liquid stool specimen per 7 day period will be accepted for testing.
● Following a positive test result, replicate specimens will only be tested after 10 days.
Blood Cultures ● A minimum of two sets (one set = one anaerobic and one aerobic bottle) should always be obtained. The minimum volume of blood needed per bottle for adults is 10 ml. Thus, the minimum volume of blood per set is 20 ml.
● Ordering one set may lead to confusion if the culture is positive for an organism that is commonly a contaminant. For example, if one set is ordered and is positive for coagulase-negative staphylococci, a common contaminant, it is impossible to determine if this represents contamination or infection. However, if two sets are ordered, and only one is positive for coagulase-negative staphylcocci, this most likely represents contamination.
● Multiple sets drawn from a single venipuncture or from a single line draw should not be considered separately.
● Cultures are monitored continuously by the laboratory using automated instrumentation.
● A preliminary report is available as soon as the specimen becomes positive; a final negative report in 5 days.
● Ideally, blood cultures should be drawn before the first dose of antibiotics, but antibiotics should not be withheld because of a delay in getting blood drawn.
● Although it is common practice to wait 30-60 minutes between blood culture draws, there are few data to support this practice. Rather, multiple draws from different venipuncture sites may be indicated.
● If a patient is persistently febrile without a defined source of infection, obtain two sets of cultures per day for 48-72 hours. Do not continue drawing daily blood cultures beyond 72 hours.
● If a vascular catheter is thought to be a potential site of infection, blood should be drawn from the catheter and the periphery. Site and time of phlebotomy should always be noted.
Respiratory Cultures
Lower respiratory tract: Appropriate specimens to identify pathogens causing disease of the lower respiratory tract (tracheitis, bronchitis, pneumonia, lung abscess, and empyema) include expectorated and induced sputum, endotracheal tube aspirations, bronchial brushings, washes, or alveolar lavages collected during bronchoscopy and pleural fluid.
Upper respiratory tract: Appropriate specimens to identify pathogens causing respiratory tract infections include samples from the nasopharynx, throat, oral ulcerations. Nares swabs and nasopharyngeal swabs and washes are not acceptable for routine bacterial culture. If Bordatella pertussis or B. parapertussis is suspected, a nasopharyngeal specimen should be submitted for B. pertussis/parapertussis PCR.
Lower respiratory tract specimens (particularly sputum) are assessed for quality (lack of contaminating oral respiratory tract flora and epithelial cells) through a Gram stain. If the specimen shows a lack of PMNs but many epithelial cells and oropharyngeal flora, the specimen will be rejected by the laboratory and another specimen must be collected for culture.
Mycobacteriology
General: Mycobacteriumspp. are typically placed into one of three groups based upon their growth characteristics and, in some cases, their phylogenetic relatedness.
1. M. tuberculosis complex: This group includes M. tuberculosis, M. bovis, M. africanum, M. microti, M. pinnipedii, and M. canettii. These organisms, which grow very slowly (14-21 days), are of extreme public health importance due to person-to-person spread.
2. Slowly growing nontuberculous mycobacteria: This group includes, among others, the M. avium complex (MAC), M. genavense, M. kansasii, and M. ulcerans.
3. Rapidly growing mycobacteria: This group includes M. fortiuitum, M. abscessus, and M. chelonae.
Staining: Due to the high mycolic acid content in their cell wall, Mycobacterium spp. stain poorly by the Gram stain method. Therefore, AFB smears for mycobacteria are screened by fluorescent Auramine O stain and confirmed positive by the Ziehl-Neelsen stain. Bacteria that stain positive with the Ziehl-Neelsen stain are called acid-fast bacteria (AFB) because they resist decolorization with acidified organic solvents and retain the carbol fuschisin dye, appearing red. The positive acid-fast stain by Ziehl-Neelsen should not be confused with a positive “modified” acid-fast stain, which is used to detect partial or weakly acid-fast aerobic actinomycetes including Nocardia, Gordonia, Rhodococcus, and Tsukamurella.
Specimen requirements: Typical specimens submitted for Mycobacteria spp isolation include sputum, tissue, or sterile body fluid (including blood). It should be noted that specimens submitted on swabs or contaminated with tap water are not acceptable for isolation of Mycobacterium spp. Ordering physicians must report positive results to the LA County Public Health Dept.
Timing: Specimens collected for AFB culture are processed at 10 am Mon-Sat by the Microbiology laboratory. This process takes 3-4 hours to perform. Following decontamination, a direct smear is performed on each specimen, and cultures are set up. The smear refers to the acid fast stain, which is also known as a Ziehl-Neelsen stain. Positive smears are called to the ordering physician by the laboratory. The smear is only ~30% sensitive, and many results must await the growth of the organism, which may take up to 8 weeks. Positive cultures are first tested using a DNA probe test (not a PCR-based approach) to detect Mycobacterium tuberculosis complex, M. kansasii, M. avium-complex, and M. gordonae. All other Mycobacterium species are identified using conventional biochemical techniques and DNA sequencing.
Susceptibility testing: Susceptibility testing for slow-growing mycobacterial isolates is a sendout test. Susceptibility testing is routinely performed on M. tuberculosis. Susceptibilities are not routinely performed on non-M. tuberculosis isolates unless requested by the clinician. Turn around time is typically 2-4 weeks. A molecular beacon test is also available for the screening of isonizid (INH) and rifampin resistance in M. tuberculosis, and associated with a 3-5 day turn around time; this test is also a send-out. Susceptibility testing is routinely performed in-house for the rapidly growing Mycobacteria.
Mycobacterium Amplified Direct Test: A PCR test is available as a send-out test for detection of M. tuberculosis complex directly from patient specimens. Approved specimens include sputum and BAL. It is recommended that all patients with a high clinical suspicion of TB be tested by this method because of the high sensitivity/specificity.
Virology Virus detection: There are four general ways in which viral infections can be detected: culture, direct viral antigen detection, serology, or nucleic acid detection. Detailed information about specific tests, including specimens accepted, dates run, and turn-around time, can be obtained from the online lab manual available at http://www.crlonline.com/crlsql/servlet/crlonline.
Culture: Viral culture is based upon the inoculation of specimen into specific cell lines and detection of a cytopathic effect (CPE) within those cells; specific CPE is representative of a specific virus. This initial observation is then typically confirmed using virus-specific antibody. Final results are available within 21 days. Influenza, parainfluenza, measles, mumps, rhinovirus, and rubella require special techniques for detection and should be noted as the suspected agent on the requisition
Nucleic Acid Amplification Test: Viruses that cause respiratory infections can be detected using an FDA-approved Respiratory Viral Panel test. This test is capable of simultaneous detection and identification of eighteen respiratory viruses using a qualitative nucleic acid multiplex PCR assay. Viruses detected by this methodology include Influenza A/B, Respiratory Syncytial Virus (RSV), Human Metapneumovirus, Rhinovirus, Adenovirus, and Parainfluenza virus. The acceptable specimen is a nasopharyngeal swab placed in viral transport media, or 2-3 ml of nasopharyngeal wash, or bronchoalveolar lavage (BAL). The test is performed Tuesdays and Fridays, with additional days added during respiratory virus season. The test should be reserved for patients in whom detection of these viruses will impact clinical management, such as critically ill patients or transplant patients. This test should not be used as a test of cure.
Direct viral antigen detection: HSV and VZV can be detected directly from skin and mucous membrane lesions using a direct fluorescent antibody (DFA) test. Specimens should be collected during the acute phase of the disease. For best results, samples should be collected from early stage vesicular lesions rather than ulcerative or crusted lesions. Information on how to collect an appropriate specimen can be found at http://www.crlonline.com/crlsql/servlet/crlonline, or by phoning the laboratory at extension 42767.
Serology: Both IgM (acute) and IgG antibody titers can be assessed for a number of viral infections including: Epstein Barr Virus (EBV), CMV, measles, mumps, and West Nile Virus (sent out). Detection of antibody to HIV is by chemiluminescent assay and confirmed by Western blot. Contact the laboratory at 42767 for specific questions.
Nucleic acid detection: A number of viruses can also be detected using molecular methodologies. Specific questions regarding specimen collection, etc. should be discussed with the microbology laboratory at 310-794-2767. Presently, the laboratory test in-house HSV, VZV, CMV, EBV, BK, HIV, Hepatitis B, and Hepatitis C. Parvovirus, HHV-6, Enterovirus, JC and others are available as send-outs. Quantitative viral load tests are also available for EBV, CMV, BK, and HIV.
Specimen collection: With a few exceptions (listed below) specimens sent to the laboratory for viral culture should be collected either using a swab transported in viral transport medium or within viral transport media. For instance, cultures for HSV and VZV from lesions should be collected using a swab and sent to the laboratory in viral transport medium. It is important to note that these swabs are distinct from the typical swab for bacterial culture. All tissue specimens should be placed in viral transport medium--it is best not to use a swab when collecting tissue. The three exceptions when viral cultures do NOT need to be in viral transport medium are: 1) a nasal wash or respiratory virus culture; 2) blood for CMV; and 3) sterile fluid (such as CSF) where the specimen should not be diluted. Sterile fluids not placed in viral transport media should be kept at 4°C until transported to the microbiology laboratory. However, if both bacterial and viral identification is requested on a sterile body fluid (e.g. CSF), the specimen must NOT be refrigerated as the los of bacterial viability is likely.
Mycology Specimen collection: The ideal specimens for fungal isolation are tissue, sterile body fluid, or blood. If a tissue specimen is to be tested for the presence of fungi, it is important that part of the specimen is sent to the microbiology laboratory before the specimen is fixed in formalin for histological examination. Sending tissue specimens to both Pathology and the Microbiology laboratory greatly improves the diagnostic value of both findings.
Blood to be tested for fungi should be added to a separate blood culture bottle (Bactec Myco/F Lytic bottle) that is specially formulated for fungal and mycobacterial growth. Note that Candida species will grow well in standard conventional bacterial blood culture media and special fungal blood cultures are not necessary. It is important to note that the growth of moulds from specimens that originate from non-sterile sites should be interpreted with caution. In many cases, saprophytic moulds are contaminants.
Timing of reports: Moulds may take 3-4 weeks to grow, whereas yeasts grow rather rapidly and can usually be identified within 3-5 days. Tissue, biopsy, bone marrow, and autopsy specimens will be finalized at 6 weeks; all other specimens will be finalized at 4 weeks.
Susceptibility testing: Yeast susceptibility testing is performed using a microtiter broth dilution method. It is used to determine antifungal susceptibility (MIC) of rapidly growing yeasts including Candida species from sterile sites including blood, CSF, pleural fluid, etc. Mould isolates may be tested for antimicrobial susceptibility in extreme conditions only, and are sent to the San Antonio Fungal Testing reference laboratory for evaluation when requested. Please call the Mycology laboratory if susceptibility testing is desired on a particular isolate (310-794-2770)
Parasitology Ova and Parasites: An O&P test should be ordered on patients presenting with a history of chronic diarrhea (>10 days), especially if there is appropriate epidemiologic history. It is rarely appropriate to order an O&P test if the patient develops diarrhea while in the hospital. Physicians must report the following organisms to the Public Health Department: Entamoeba histolytica, Entamoeba histolytica/E.dispar, Giardia lamblia, and Cryptosporidium. One negative result does not rule out the possibility of parasitic infestation. Up to three specimens collected on separate days should be submitted. Routine ova and parasites exam does not include Cryptosporidium, Isospora, Cyclospora, or Microsporidia. Separate tests must be requested for these organisms.
Malaria smears: Thick and thin blood smears are prepared and evaluated for blood parasites such as Plasmodium and Babesia. Please call the Parasitology laboratory at 310-794-2770 with any questions. Consultation with the microbiology on call is recommended in order to ensure the optimal recovery and interpretation of blood smears. STAT smears are available with a 4-hour turn-around time. Note that one negative blood exam does not rule out an infection due to blood parasites. Babesia sp and Plasmodium sp must be reported to the LA County Public Health Department.
Ectoparasites: The microbiology laboratory also identifies insect vectors associated with human disease (e.g. lice, ticks, scabies). Physicians must report positive results for Sarcoptes scabiei to the LA County Public Health Department.
Antimicrobial Fundamental Concepts Pharmacodynamics and Therapeutic Drug Monitoring Pharmacokinetics versus pharmacodynamics
Pharmacokinetics mathematically describe the relationship of antibiotic concentration to time. Terminology that is typically associated with pharmacokinetics includes: absorption, distribution, metabolism, elimination, half-life, volume of distribution, and area under the concentration-time curve (AUC).
Pharmacodynamics describe the relationship of antibiotic concentration to pharmacologic effect or microorganism death. The three main pharmacodynamic parameters that are used are the peak to minimal inhibitory concentration ratio (peak/MIC), the AUC to MIC ratio (AUC/MIC), and the time the drug concentration remains above the MIC (T>MIC).
Concentration independent versus concentration dependent
Concentration independent (time dependent) means that the rate and extent of microorganism killing remain unchanged regardless of antimicrobial concentration. The pharmacodynamic parameter that is most often predictive of outcome for concentration independent drugs is T>MIC, although the AUC/MIC can be used because the AUC takes both the antimicrobial concentration and time into account. Examples of concentration independent antimicrobials include: beta-lactams, vancomycin, macrolides, aztreonam, carbapenems, clindamycin, tetracyclines, quinupristin/dalfopristin, flucytosine, and azole antifungals.
Concentration dependent (time independent) means that the rate and extent of microorganism killing are a function of the antimicrobial concentration (increase as the concentration increases). The pharmacodynamic parameter that is most often predictive of outcome for concentration dependent drugs is peak/MIC, although the AUC/MIC can be used because the AUC takes both the antimicrobial concentration and time into account. Examples of concentration dependent antimicrobials include: fluoroquinolones, aminoglycosides, and amphotericin B.
Bacteriostatic activity versus bactericidal activity
Bacteriostatic activity refers to the inhibition of bacterial growth, while bactericidal activity refers to killing the bacteria.
Minimum inhibitory concentration (MIC) – The MIC is defined as the lowest concentration of antibiotic that completely inhibits growth of the specific organism being tested.
Minimum bactericidal concentration (MBC) – The MBC is defined as the lowest concentration of antibiotic at which bacteria are killed.
Most of the available evidence supports the preferential use of a bactericidal agent when treating endocarditis, meningitis or osteomyelitis. However, data do not exist to support this practice for other infectious diseases.
Pharmacodynamic properties do not remain constant for all antimicrobials in a class for all microorganisms. In other words, if a drug is concentration dependent and bactericidal against one organism, that does not mean that it, or all the other drugs in its class, are concentration dependent and bactericidal against all organisms. However, because of a lack of data characterizing the pharmacodynamic properties of various antimicrobials against several different organisms, we usually lump antimicrobials into one category.
Vancomycin Dosing
Vancomycin is considered to be a concentration independent or time dependent killer of bacteria. Therefore, increasing antibiotic concentrations beyond the therapeutic threshold will not result in faster killing or eliminate a larger portion of the bacterial population. Vancomycin dosing should be based upon actual body weight (ABW), is generally used at doses of 10-20 mg/kg, and dosing intervals should be renally adjusted. See separate section on Vancomycin Dosing.
“Double coverage”
The use of “double coverage” (two antibiotics used to provide coverage for the same organism) is based upon the following assumptions: the combination provides a broad spectrum of coverage for empiric treatment, before you know the identification and susceptibility of the offending pathogen; the combination may provide additive or synergistic effects against the pathogen; or the combination of antibiotics may decrease or prevent the emergence of resistant bacteria.
Gram-negative Bacteria
Inappropriate initial therapy has been shown to cause increased morbidity and mortality, specifically related to Gram-negative infections (usually Pseudomonas and Acinetobacter spp.). Thus, double coverage serves the purpose of providing broad spectrum initial empiric coverage until susceptibility data are known. No evidence exists to support the superiority of combination therapy over monotherapy for Gram negative infections once susceptibilities are known. Thus, once culture identification and susceptibilities have been reported, de-escalation to a single agent is strongly recommended.
Synergy
● Occurs when inhibitory or bactericidal activity of combination therapy is greater than would be expected from the sum of the activities of the individual agents
● Synergy for Gram-negative infections is of major value only when the bacterium is resistant to one or both of the drugs in the combination.
● Synergy has been best established for beta-lactam and aminoglycoside combinations.
● Synergy between other drug combinations is less predictable and has unclear clinical significance.
Prevention of emergence of resistance
● Emergence of resistance on therapy is uncommon, occurring in 5–10% of infections treated.
● Emergence of resistance to beta-lactams while on therapy with these agents occurs in ~20% of patients infected with organisms with inducible beta-lactamases (Serratia, Enterobacter, Citrobacter, Acinetobacter); beta-lactams are best avoided in these patients if other options are available.
● Emergence of resistance is more common in pneumonia and osteomyelitis due to decreased antibiotic penetration at these sites; attention should be given to appropriate dosing in these patients.
● The addition of additional agents may lead to increased toxicity from adverse drug reactions without preventing emergence of resistance.
Broadening of initial empiric coverage
● Should be considered in patients with life-threatening infections (ventilator-associated pneumonia, sepsis).
● Second agent should offer additional coverage and generally should be an aminoglycoside at UCLA.
● Coverage MUST be narrowed based on culture results; negative cultures can be used to rule out infections with most organisms.
Data regarding combination therapy
● An early study by Hilf suggested that combination therapy was superior to monotherapy in patients with Pseudomonas bacteremia BUT 84% of monotherapy patients received inadequate monotherapy with an aminoglycoside. Five more recent studies have not shown a difference in mortality when patients received appropriate monotherapy for Pseudomonas bacteremia.
● Recent prospective studies have not shown a benefit to combination therapy over monotherapy in the treatment of serious Gram-negative infections in both non-neutropenic AND neutropenic patients
● Two recent meta-analysis showed no difference in outcomes of patients with sepsis or febrile neutropenia treated with beta-lactams alone vs beta-lactam/aminoglycoside combinations although patients in the latter group had a higher incidence of nephrotoxicity.
Recommendations for use of combination therapy
● Data suggest that monotherapy is sufficient for the treatment of most Gram-negative infections.
● The use of 2 agents to treat proven or suspected Gram-negative infections should be limited to the following situations:
○ Empiric treatment of serious infections manifested by hypotension, pressor dependence, or mechanical ventilation (to broaden spectrum) until cultures return
○ Documented infection with a resistant Gram-negative organism (particularly Pseudomonas, Acinetobacter, Citrobacter, Enterobacter, and Serratia when antibiotic penetration to the site of infection is poor (pneumonia, osteomyelitis). Consideration should be given to stopping one of the agents after 5-7 days of therapy when the bacterial burden has decreased.
○ Documented infection with a highly-resistant organism only after synergy testing shows an advantage to a beta-lactam/aminoglycoside combination. Infectious Diseases consult strongly advised.
● The second agent should be an aminoglycoside in most cases. Fluoroquinolone resistance is common among Gram-negative organisms at UCLA.
● Double beta-lactam combinations (e.g. zosyn + meropenem) should be avoided.
References:
Am J Med 1989;87:540.
Antimicrob Agents Chemother 1994;38(6):1309.
Antimicrob Agents Chemother 1997;41:1127.
BMJ 2003;326:1111. BMJ 2004;328:668.
Clin Infect Dis 1995;20(5):1217.
Int J Antimicrob Agents 1999;11:7.
Pharmacother 1995;15(3):279.
Anaerobes Anaerobic pathogens are normal flora of the oral cavity and the gastrointestinal tract. While oral anaerobic flora are mostly Gram-positive organisms such as Peptococcus and Peptostreptococcus spp., the principal anaerobic intestinal flora are Gram-negative bacilli such as Bacteroides fragilis, Prevotella melaninogenica, and Fusobacterium spp. Gram-positive oral anaerobes are widely covered by most of the orally-available agents, including penicillin. However, antibiotic activity against the most common intestinal anaerobic bacteria, Bacteroides spp., is variable.
Anaerobic coverage is indicated in a variety of infectious processes, including but not limited to aspiration pneumonia, intra-abdominal infection, gynecologic infection, and diabetic foot ulcer infection. Antimicrobial agents with appreciable anaerobic activity include the following: Amoxicillin/clavulanate, Ampicillin/sulbactam, Cefotetan, Cefoxitin, Clindamycin, Ertapenem, Imipenem, Meropenem, Metronidazole, Moxifloxacin, Piperacillin/tazobactam, Tigecycline.
Double anaerobic coverage is the use of any combination of the above agents, which is prevalent at UCLA. A common combination is piperacillin/tazobactam + metronidazole. Redundant anaerobic coverage is a common problem intervened upon by the Antimicrobial Stewardship Program.
Double anaerobic coverage is not necessary and puts the patient at risk for additional drug toxicities. No data or guidelines support double anaerobic coverage in clinical practice, with two clinical exceptions:
Exceptions:
1. Metronidazole can be added to another agent with anaerobic activity when being used to treat Clostridium difficile infection.
2. Clindamycin can be added to another agent with anaerobic activity when being used for the treatment of necrotizing fasciitis.
Laboratory and Clinical Toxicity Monitoring
| Medication | Select Toxicities | Minimum Laboratory Monitoring | Clinical Monitoring |
| Aminoglycosides (gentamicin, tobramycin, amikacin) | Nephrotoxicity, auditory toxicity, vestibular toxicity, neuromuscular blockade | Cr at least 2x/week (for dose-adjustment and nephrotoxicity assessments), serum levels if therapy is to continue >72 hours | Baseline and periodic hearing and vestibular function (questioning audiologic testing with prolonged therapy) |
| Aztreonam | GI effects, hypersensitivity | Cr weekly (for dose-adjustment assessment) | Hypersensitivity, diarrhea |
| Carbapenem (meropenem, ertapenem) | Hypersenstivity, GI effects, C. difficile, seizures (especially with high doses or doses not adjusted for renal function) | Cr weekly (for dose-adjustment assessment) | Hypersensitivity, GI effects, seizures (rare) |
| Cephalosporins Ceftriaxone | GI effects, hypersensitivity reactions, C. difficile As above, plus biliary sludging, gallstones | For IV cephalosporins, Cr weekly except for Ceftriaxone, which does not require dose adjustment for renal function Consider LFTs with prolonged use | Hypersensitivity, diarrhea, other GI effects As above, plus signs of biliary sludge or gallstones |
| Clindamycin | Diarrhea, C. difficile | Not routinely indicated | Hypersensitivity, GI effects, photosensitivity |
| Dalfopristin/quinupristin | Pain or inflammation at infusion site, arthralgia or myalgia, hyperbilirubinemia | LFTs weekly | Phlebitis, arthralgias, myalgias |
| Daptomycin | GI effects, hypersenstivity, headache, elevated CK, myalgias, rarely rhabdomyolysis | CK weekly, Cr weekly (dose adjustment assessment) | Hypersensitivity, GI effects, myalgias, rhabdomyolysis |
| Fluoroquinolone (ciprofloxacin, levofloxacin) | GI effects, arthropathy (especially in pediatric patients), tendon rupture, prolongation of QT interval, CNS effects (esp with ciprofloxacin) | Consider periodic Cr and LFTs with prolonged use | Hypersensitivity, GI effects, drug interactions (warfarin), prolongation of QT interval (amiodarone), CNS effects, photosensitivity |
| Linezolid | Myelosuppression, diarrhea, rash, optic neuritis, peripheral neuropathy | CBC baseline and weekly, consider periodic LFTs with prolonged use | Hypersensitivity, GI effects, neuropathy, drug interactions (serotonergic drugs) |
| Macrolide (azithromycin, clarithromycin, erythromycin) | GI effects, cholestatic jaundice, QT prolongation, allergic reaction | Consider periodic LFTs with prolonged use; baseline Cr with clarithromycin (dose-adjustment assessment) | Hypersensitivity, GI effects, drug interactions, QT prolongation with risk factors |
| Metronidazole | Nausea, diarrhea, disulfiram-like reactions with alcohol, metallic taste, reversible neutropenia | Consider baseline LFTs | GI effects. Avoid alcohol |
| Penicillin class | |||
| Tetracycline class (doxycycline, minocycline) | Photosensitivity, permanent staining of developing teeth (avoid in pregnant women and children <8y), GI effects, rash, vestibular toxicity (minocycline) | Consider periodic LFTs with prolonged use | Hypersensitivity, diarrhea, GI effects, drug interactions, vestibular toxicity (minocycline), photosenstivity (avoid prolonged sun exposure) |
| Tigecycline | Nausea and vomiting | LFTs weekly | GI effects |
| TMP/SMX | Nausea, vomiting, hypersensitivity reactions, bone marrow suppression, hyperkalemia | With high dose: consider baseline and periodic measurement of Cr (dose-adjustment and nephrotoxicity assessment), CBC, K, LFTs | Hypersensitivity, GI effects |
| Vancomycin | Ototoxicity, re man syndrome, nephrotoxicity (usually in combination with other nephrotoxins), phlebitis, reversible neutropenia | Cr baseline and weekly (for potential dose-adjustment and nephrotoxicity assessment), CBC weekly, serum levels as appropriate | Phlebitis, hypersensitivity, GI effects |
| Antifungal agents | |||
| ABLC | Lower incidence of nephrotoxicity than amphotericin B deoxycholate, infusion-related effects, electrolyte disturbances (hypokalemia, magnesemia) | Twice-weekly Cr, K, Mg; weekly LFTs and CBC | Infusion-related effects |
| Triazole antifungals (fluconazole, itraconazole, voriconazole, posaconazole) Voriconazole | GI effects, hepatitis, QT prolongation, hypersensitivity Transient visual disturbances, cyclodextrin vehicle accumulation with IV formulation in patients with renal dysfunction (clinical significance of risk/benefit unknown) | Baseline and periodic LFTs and Cr (dose-adjustment assessment with fluconazole); cyclodextrin vehicle accumulation with IV voriconazole Serum levels as indicated | GI effects, prolongation of QT interval with risk factors, hypersensitivity, photosensitivity, drug-drug interactions As above and visual side effects, hallucinations |
| Caspofungin | Facial flushing or swelling (histamine mediated but rare), hypersensitivity, hepatitis | LFTs weekly | Hypersensitivity, drug-drug interactions |
| Antiviral Agents | |||
| Cidofovir | Renal impairment, neutropenia, ocular hypotonia, headache, asthenia, alopecia, rash, GI effects | Cr (also give saline load and probenecid), CBC, UA all 2x/week and before each dose | GI effects, hypersensitivity (especially with probenecid) |
| Foscarnet | renal impairment, electrolyte disturbances, seizures, GI effects | Cr 2x/week (dose-adjustment and nephrotoxicity assessments), electrolytes weekly | GI effects, hypersensitivity |
| Ganciclovir or valganciclovir | Myelosuppression, GI effects | CBC 1-2x/week, Cr weekly (dose-adjustment assessment | GI effects |
| Acyclovir or valacyclovir | Malaise, nausea, vomiting, diarrhea, phlebitis (with IV acyclovir), nephrotoxicity and CNS effects with high-dose IV therapy | Cr weekly with IV acyclovir (dose-adjustment and nephrotoxicity assessment) | Phlebitis, CNS effects (IV), GI effects |
Ampicillin/sulbactam (Unasyn)
Ampicillin/sulbactam is a beta-lactam/beta lactamase inhibitor combination antibiotic. It has activity against MSSA, streptococci, enterococci (that are ampicillin-susceptible) and anaerobes. Its activity against gram-negative organisms is limited; an increasing number of E. coli and Proteus isolates are now resistant. Because of this, its use for intraabdominal infections is not advised although it previously was widely used for this purpose.
Acceptable uses
● Treatment of human or animal bites if parenteral therapy is needed
● Treatment of oral infections
● Treatment of lung abscess
● Treatment of culture-negative endocarditis (ID consult advised)
Unacceptable uses
● Empiric treatment of biliary tract infections, diverticulitis, or secondary/peritonitis/GI perforation. Use should be limited to infections that are proven to be susceptible
Dose
1.5 - 3 g IV q6-8h (higher doses may be used for multi-drug resistant Acinetobacter
Colstin (Colistimethate)
Colistin is a polymixin antibiotic. It has activity against susceptible Acinetobacter and Pseudomonas but no activity against Proteus, Serratia, Providencia, Burkholderia, Gram-negative cocci, Gram-positive organisms, or anaerobes.
Acceptable uses
● Management of infections due to multi-drug resistant Acinetobacter and Pseudomonas on a case-by-case basis. ID consult strongly advised.
Unacceptable uses
● Monotherapy for empiric treatment of suspected gram-negative infections
● Prophylactic therapy
Dose
5-15 mg/kg/day divided into 2-3 doses, adjust for renal function and dialysis (see Table)
Toxicity
● Renal impairment, neuromuscular blockade, neurotoxicity
● Monitor creatinine a minimum of twice weekly.
Daptomycin
Daptomycin is a lipopeptide antibiotic. It has activity against most strains of staphylococci (including MRSA) and streptococci (including VRE). It does NOT have activity against Gram-negative organisms. It is ineffective for pulmonary parenchymal infections.
Acceptable uses (ID consult or ASP approval is required)
● Bacteremia or endocarditis caused by MRSA or methicillin-resistant coagulase-negative staphylococci in a patient with a serious allergy to vancomycin
● Therapy for MRSA infections (other than pneumonia) in which the MIC of vancomycin is ≥2 mcg/mL
● Bacteremia or endocarditis caused by MRSA in a patient failing vancomycin therapy defined as:
○ Clinical decompensation after 3-4 days● Salvage therapy for VRE infections other than pneumonia, on a case-by-case basis
○ Failure to clear blood cultures after 7-9 days despite vancomycin troughs of 15-20 mcg/mL
○ Select cases in which the MIC of vancomycin is ≥ 2 mcg/ml
Unacceptables uses
● Treatment of pneumonia of any kind, as daptomycin is inactivated by pulmonary surfactant
● Initial therapy for gram-positive infections
● VRE colonization of the urine, respiratory tract, wounds, or drains
● Convenience due to ease of dosing compared to vancomycin
Dose
● Bacteremia: 6-12 mg/kg IV q24h
● Endocarditis: 6-12 mg/kg IV q24h
● Dose adjustment is necessary for CrCl <30 ml/min (see Table)
Toxicity
Myopathy (defined as CK more than 10 times ULN without symptoms or more than 5 times ULN with symptoms)
Monitoring: total CK and creatinine weekly
Ertapenem
Ertapenem is a carbapenem antibiotic. It has in vitro activity against many gram-negative organisms including those that produce extended spectrum beta-lactamases (ESBL), but it does not have activity against Pseudomonas or Acinetobacter. Its anaerobic and gram-positive activity is similar to that of other carbapenems, except that it does not active against Enterococcus.
Acceptable uses
● Mild to moderate intra-abdominal infections (biliary tract infections, diverticulitis, secondary peritonitis/GI perforation)
● Moderate diabetic foot infections
● Moderate surgical-site infections following contaminated procedures
● Urinary tract infections caused by ESBL-producing organisms
● Pyelonephritis due to ESBL-producing organisms
● Home-going therapy for patients with mixed (polymicrobial) infections caused by susceptible organisms
Unacceptable uses
● Infections in which Pseudomonas or Acinetobacter is suspected
Dose
● 1 gm IV q24h, must adjust for renal function and dialysis (see Table)
Toxicity
● Diarrhea, nausea, headache, phlebitis/thrombophlebitis
Fosfomycin
Fosfomycin is a synthetic, broad-spectrum, bactericidal antibiotic with in vitro activity against large numbers of gram-negative and gram-positive organisms including E. coli, Klebsiella spp, Proteus spp, Pseudomonas spp, and VRE. It does not have activity against Acinetobacter. Fosfomycin is available as an oral formulation only and its pharmacokinetics allow for one-time dosing.
Acceptable uses
● Management of uncomplicated UTI in patients with multiple antibiotic allergies and when oral therapy is indicated
● Uncomplicated UTI due to VRE
● Salvage therapy for UTI due to multi-drug resistant gram-negative organisms (e.g. ESBL, Pseudomonas) on case by case basis.
Unacceptable uses
● Never use for management of infections outside the urinary tract because fosfomycin does not achieve adequate concentrations at other sites.
Dose
● Uncomplicated UTI: 3g (1 sachet) PO once.
● Complicated UTI: 3g (1 sachet) PO every 3 days, up to 21 days of treatment.
● Powder should be mixed with 90-120 mL of cold water, stirred to dissolve and taken immediately.
Toxicity
● Diarrhea, nausea, headache, dizziness, asthenia and dyspepsia
Linezolid
Linezolid is an oxazolidinone. It has activity against most strains of staphylococci (including MRSA) and streptococci (including VRE). It does NOT have activity against gram-negative organisms. It is available IV and PO and is 100% bioequivalent.
Acceptable uses
● Documented vancomycin-intermediate Staphylcoccus aureus (VISA) or vancomycin-resistant (VRSA) infection
● Documented MRSA or methicillin-resistant coagulase-negative staphylococcal infection in a patient with a serious allergy to vancomycin
● Documented MRSA or methicillin-resistant coagulase-negative staphylococcal infection in a patient failing vancomycin therapy (as defined below):
● Bacteremia/endocarditis: failure to clear blood cultures after 7-9 days despite vancomycin troughs of 15-20 mcg/mL. Should be used in combination with another agent as linezolid is bacteriostatic, not bacteriocidal.
● Pneumonia: worsening infiltrate or pulmonary status in a patient with documented MRSA pneumonia after 2-3 days of vancomycin therapy or if the MIC of vancomycin is ≥ 2 mcg/ml. ID consultation strongly advised.
● High suspicion of CA-MRSA necrotizing pneumonia in a seriously ill patient.
● Documented VRE infection (not colonization)
● Post-neurosurgical shunt infection, meningitis or ventriculitis due to staphylococcal species or VRE
●Gram-positive cocci in chains in a blood culture in an ICU, solid oncology, or transplant patient known to be colonized with VRE
● Treatment of certain atypical mycobacterial or nocardial infections. ID consultation strongly advised.
Unacceptable uses
● Prophylaxis
● Initial therapy for staphylococcal infection
● VRE colonization of the stool, urine, respiratory tract, wounds, or drains
Dose
● 600 mg IV/PO q12h
Toxicity
● Bone marrow suppression (usually occurs within first 2 weeks of therapy). Pyridoxine is of no benefit
● Optic neuritis and irreversible sensory motor polyneuropathy (usually occurs with prolonged therapy >28 days)
● Case reports of lactic acidosis
● Case reports of serotonin syndrome when co-administered with serotonergic agents (SSRIs, TCAs, MAOIs)
● Monitoring: CBC weekly, consider periodic LFTs with prolonged use.
Tigecycline
Tigecycline is a tetracycline derivative. It has in vitro activity against most strains of staphylococci and streptococci (including MRSA and VRE), anaerobes, and many gram-negative organisms with the exception of Pseudomonas and Proteus. It is FDA-approved for treatment of skin and skin-structure infections and intraabdominal infections. Peak serum concentrations do not exceed 1 mcg/mL which limits its use for treatment of bacteremia.
Acceptable uses (Infectious Disease or ASP approval required)
● Management of intra-abdominal infections in patients with contraindications to both beta-lactams and fluoroquinolones
● Management of infections due to multi-drug resistant gram-negative organisms including Acinetobacter on a case-by-case basis
● Salvage therapy for MRSA or VRE infections on a case-by-case basis
Unacceptable use
● Bacteremia and endocarditis
● Tigecycline should not be used to treat pneumonia, as unacceptably high failure rates have been reported.
Dose
● 100 mg IV once, then 50 mg IV q12h
Toxicity
● Nausea/vomiting in 25% of recipients
● Monitoring: LFTs weekly
Vancomycin
At UCLA in 2010, 36% of S. aureus isolates in inpatients were resistant to oxacillin. These data suggest that empiric use of vancomycin is advisable for an ill patient with suspected S. aureus infection. However, vancomycin should be stopped if culture data do not indicate a need for continued definite therapy (see below). Limiting prolonged or inappropriate use of vancomycin is essential. Presently vancomycin is the single most used antibiotic at UCLA, with approximately 15% of all inpatients receiving at least one day of therapy. There are few instances when continued use of vancomycin is appropriate in the absence of positive cultures. The following are recommendations for empiric, definitive, and prophylactic vancomycin therapy. Acceptable empiric use Note: therapy should be discontinued within 72 hours if criteria for definitive therapy (see below) are not met:
● Treatment of suspected community- or nosocomial-acquired bacterial meningitis
● Treatment of ventilator-associated pneumonia
● Treatment of peritoneal dialysis-related peritonitis in a severely ill patient
● Treatment of sepsis in a patient at risk for MRSA bacteremia [catheter in place, indwelling hardware, known MRSA colonization, transfer from a nursing home or subacute facility, recent (within 3 months) or current prolonged hospitalization >2 weeks]
● Treatment of surgical-site infection following placement of hardware
● Treatment of severe diabetic foot infection in a patient at risk for MRSA
● Treatment of necrotizing fasciitis
● Treatment of suspected endocarditis in a moderately or severely ill patient after appropriate blood cultures are obtained
● Treatment of gram-positive cocci in clusters in ≥ 1 set of blood cultures in a moderately or severely ill patient
● Treatment of gram-positive cocci in clusters or chains in ≥ 2 sets of blood cultures in any patient Acceptable use of definitive intravenous therapy
● Proven infection with beta-lactam resistant organisms
○ MRSA
○ Methicillin-resistant coagulase-negative staphylococcus
○ Ampicillin-resistant enterococcus (if susceptible)
○ Ceftriaxone-resistant S. pneumoniae (CSF only)
● Treatment of infections caused by gram-positive organisms in patients who have serious allergies to beta-lactam agents (see discussion of penicillin allergy) Acceptable use for definitive oral therapy
● Clostridium difficile infection (see CDI section) Acceptable use for prophylaxis
● Prophylaxis for cardiac, vascular, or orthopedic (joint replacement, spinal fusion, ORIF only) surgery with a documented reason in the chart or in patients with severe PCN allergy (no more than one pre-op and one post-op dose) Unacceptable uses for vancomycin
● Continued empiric use for presumed infection with negative cultures
● Treatment of a single-positive blood culture for coagulase-negative staphylococci
● Routine surgical prophylaxis except as above
● Empiric treatment for first fever in neutropenic patients without evidence of catheter-related bloodstream infection, severe mucositis, or history of MRSA
● Prophylaxis for infection or colonization of indwelling intravascular or intracranial catheters
● Selective decontamination of the digestive tract
● Eradication of MRSA colonization
● Routine prophylaxis for patients on continuous ambulatory peritoneal dialysis or hemodialysis
● When chosen only for convenience of dosing for treatment of infections caused by beta-lactam susceptible organisms in patients who have renal failure
● Topical application or irrigation Dosing
● Goal trough of 10-20 mcg/mL. See vancomycin dosing section.
Definitions:
● Definite: invasive aspergillosis is established by positive culture or histopathology for aspergillosis from tissue obtained during an invasive procedure. Washings, brushings, or suctioning of secretions do NOT represent invasive procedures.
● Probable: aspergillosis is indicated by a positive galactomannan assay from serum or BAL or positive culture for aspergillus species AND clinical evidence suggestive of aspergillosis.
● Possible: aspergillosis is indicated by a positive galactomannan assay from serum or BAL or radiographic findings highly suggestive of aspergillosis in a compatible host (follow-up diagnostic studies are highly recommended).
● Refractory: means disease progression or failure to improve despite at least 96 hours of treatment with Voriconazole or an IV Amphotericin B product (deoxycholate or lipid-based product).
Caspofungin
Aspergillosis Acceptable uses
● Infusional toxicity or acute renal failure on ABLC and intolerance to voriconazole defined as serious hepatotoxicity, persistent visual disturbance, or allergic reaction.
● Refractory disease for use in combination with voriconazole or ABLC for definite or probable invasive pulmonary aspergillosis in patients who are refractory to voriconazole or ABLC alone (ID consult advised)
Unacceptable uses
● Caspofungin alone or in combination with other antifungal agents is not recommended for empiric therapy in patients with CT findings suggestive of aspergillosis (e.g., possible aspergillosis) without plans for diagnostic studies
● Caspofungin does not have good in vitro activity against zygomycoses (Mucor, Rhizopus, Cunninghamella, etc.)
Candidiasis Acceptable uses
● Treatment of invasive candidiasis due to C. glabrata or C. krusei
● Treatment of invasive candidiasis in patients who are NOT clinically stable due to candidemia or have received prior long-term azole therapy.
● Alternative treatment of recurrent esophageal candidiasis
● Alternative treatment of endocarditis
Unacceptable uses
● Caspofungin has poor penetration into the CNS and urinary tract. It should be avoided for infections involving those sites. Positive urine cultures for resistant Candida in catheterized patients usually represent colonization and should not be treated with caspofungin
● Monotherapy for zygomycoses (Mucor, Rhizopus, etc.)
Neutropenic Fever ● Caspofungin can be used for neutropenic fever in patients who are not suspected to have aspergillosis or zygomycosis
Dose ● 70 mg IV once, then 50 mg IV daily
Toxicity
● Infusion-realted reactions (rash, pruritis), phlebitis, headache, nausea and vomiting, elevations in hepatic enzymes
● Monitoring: AST/ALT/bilirubin at baseline and every 1-2 weeks
Posaconazole
Posaconazole is a broad spectrum azole anti-fungal agent. It has in vitro activity against Candida, Aspergillus, Zygomycosis and Fusarium spp.
Acceptable uses
● Treatment of invasive zygomycosis in combination with Amphotericin B
● Monotherapy for zygomycosis after 7 days of combination therapy with Amphotericin B
● Note: posaconazole requires up to 7 days to achieve steady state concentrations. ID consult is advised.
Unacceptable uses
● Candidiasis/neutropenic fever
● Primary treatment of aspergillosis
Dose
Note: each dose should be given with a full meal or with liquid nutritional supplements if patients cannot tolerate full meals.
● Loading dose: 200 mg PO q6h for 7 days
● Maintenance dose: 400 mg PO q8-12h
Drug Interactions
● Posaconazole is an inhibitor and is metabolized by cytochrome P4503A4; therefore, co-administration with other agents that are cytochrome P450 substrates, inducers, or inhibitors will result in significant drug interactions.
● You must check for potential drug interactions when initiating Posaconazole therapy or starting a new medication in patients already receiving Posaconazole therapy.
● Administration of the following agents with Posaconazole is contraindicated:
○ Terfenadine, Astemizole, Pimozide, Cisapride, Quinidine, Sirolimus, Halofantrine and ergot alkaloids
● Posaconazole inhibits metabolism of the following agents. Dose reductions and close monitoring are recommended when Posaconazole is used with agents concomitantly:
○ Tacrolimus – reduce Tacrolimus dose to ⅓ and monitor levels
○ Cyclosporine – reduce Cyclosporine dose to ¾ and monitor drug level
○ Midazolam – consider dose reducing
○ Cimetidine, Rifabutin, Efavirenz and Phenytoin – unless the benefit outweighs the risk, AVOID concomitant use. If used together, monitor effect of the drugs and consider decreasing dose when Posaconazole is added
○ Statins (avoid Lovastatin and Simvastatin), vinca alkaloids, calcium channel blockers, Digoxin, Atazanavir, Ritanovir, QTc prolonging drugs (e.g. Amiodarone and Erythromycin) – monitor effect of the drugs and consider decreasing dose when Posaconazole is added
○ Cimetidine, Rifabutin, Phenytoin, Efavirenz, Esomeprazole, Metoclopramide may decrease Posaconazole blood levels.
Toxicity
● GI upset (~40%), headaches, elevation in hepatic enzymes. Rare but serious effects include QTc prolongation
● Monitoring: Hepatic enzymes at baseline and every 1-2 weeks after
Voriconazole
Note: Voriconazole does not cover zygomycoses (Mucor, Rhizopus, Cunninghamella, etc)
Acceptable uses (ID consult advised):
● Aspergillosis (please refer to prior definitions)
● Oncologic neutropenic and BMT populations:
○ Definite (biopsy-proven) invasive non-zygomycete filamentous fungal infections
○ Probable invasive non-zygomycete filamentous fungal infections
○ Empiric therapy in patients with possible aspergillosis (follow-up diagnostic studied are highly recommended
● Other patient populations:
○ Definite infections or as otherwise deemed appropriate after consultation with the Infectious Diseases service or the ASP
○ Pseudallescheria boydii (Scedosporim spp), Fusarium spp. Voriconazole is recommended as first-line therapy
○ Alternative therapy for C. krusei if susceptible and oral therapy is desired in stable patient.
Unacceptable uses:
● Candidiasis / Neutropenic fever: Voriconazole should not be used as first-line therapy for the treatment of candidiasis or for empiric therapy in patients with neutropenic fever.
● Treatment of positive urine cultures due to resistant Candida spp.
Dose
● Loading dose: 6 mg/kg IV/PO q12h x 2 doses
● Maintenance dose: 4 mg/kg IV/PO q12h
● Patients receiving concomitant phenytoin or efavirenz should receive following maintenance doses of voriconazole due to induced hepatic clearance by phenytoin and efavirenz.
○ Intravenous: 5 mg/kg q12h
○ Oral: 400 mg q12h (wt >40 kg) or 200 mg Q12h (wt <40kg)
○ Efavirenz dose should be decreased to 300 mg PO daily
○ Monitor phenytoin levels and adverse events
○ Dose escalation may be necessary for some patients due to subtherapeutic levels
● Voriconazole IV is packaged with a cyclodextrin vehicle which can accumulate in patients with renal dysfunction. The clinical significance of risk vs benefit of using IV voriconazole in patients with renal dysfunction is unknown.
Therapeutic monitoring
● Obtaining voriconazole trough levels should be considered in patients who are:
○ not responding to therapy after at least 5 days of therapy using a mg/kg dosing strategy
○ receiving concomitant drugs that may increase or decrease voriconazole levels
○ experiencing adverse events due to voriconazole
○ experiencing GI dysfunction
● Voriconazole trough levels should be obtained 5-7 days after start of therapy
● Goal trough: 1-5.5 mcg/mL. Levels < 1 mcg/mL have been associated with clinical failures and levels >5.5 mcg m/mL with toxicity
Drug interactions
● Voriconazole is an inhibitor and is metabolized by cytochrome P450; therefore co-administration with other agents that are cytochrome P450 substrates, inducers, or inhibitors will result in significant drug interactions.
● You must check for potential drug interactions when initiating voriconazole therapy or starting a new medication in patients already receiving voriconazole therapy.
● Administration of the following agents with voriconazole is contraindicated:
○ Sirolimus, Rifampin, Rifabutin, Carbamazepine, Terfenadine, Astemizole, Cisapride, Pimozide, Quinidine, long-acting barbiturates, Ritonavir (400 mg BID), St. John’s Wort, and ergot alkaloids
● Voriconazole inhibits metabolism of the following agents: dose reductions and close monitoring are recommended when voriconazole is used with agents concomitantly:
○ Tacrolimus - reduce tacrolimus dose to ⅓ and monitor levels
○ Cyclosporine - reduce cyclosporine dose to ½ and monitor drug levels
○ Omeprazole - reduce omeprazole dose to ½
○ Warfarin - monitor INR
○ Ritonavir low dose (100 mg q12h) - avoid this combination unless benefit outweighs risk
○ Sulfonylureas, statins (avoid Lovastatin and Simvastatin), vinca alkaloids, calcium channel blockers, benzodiazepines (avoid midazolam and triazolam), oral contraceptives, Alfentanil, and Methadone – monitor effect of the drugs and consider decreasing dose when Voriconazole is added.
Toxicity
● Visual disturbances (~30%) usually self-limited, rash, fever, elevations in hepatic enzymes.
● Monitoring: hepatic panel at baseline and every 1-2 weeks after.
Treatment
● Bacterial meningitis is a MEDICAL EMERGENCY. ANTIBIOTICS SHOULD BE STARTED AS SOON AS THE POSSIBILITY OF BACTERIAL MENINGITIS BECOMES EVIDENT, IDEALLY WITHIN 30 MINUTES.
● DO NOT WAIT FOR CT SCAN OR LP RESULTS. IF LP MUST BE DELAYED, GET BLOOD CULTURES AND START THERAPY.
● Adjust therapy once pathogen and susceptibilities are known.
● Consider penicillin desensitization for pathogen-specific therapy in patients with severe allergies (see section on approach to patient with penicillin allergy).
● Antibiotic doses are higher for CNS infections, see dosing table below.
● Infectious Diseases consultation is recommended for all CNS infections, particularly those in which the preferred antibiotic cannot be used or in which the organism is resistant to usual therapy.
Empiric Therapy
| Host | Pathogens | Preferred Abx (see dosing table) | Alternative for serious PCN allergy (ID consult advised) |
| Immunocompetent, age < 50* | S. pneumo, N meningiditis, H influenzae | Vancomycin PLUS Ceftriaxone | Vancomycin PLUS Chloramphenicol |
| Immunocompetent, age > 50* | S. pneumo, Listeria, H. influenzae, N. meningiditis, Group B streptococci | Vancomycin PLUS Ceftriaxone PLUS Ampicillin | Vancomycin PLUS Chloramphenicol PLUS TMP/SMX |
| Immunocompromised* | S. pneumo, N. meningiditis, H. influenzae, Listeria, (gram-negatives) | Vancomycin PLUS Cefepime PLUS Ampicillin | Vancomycin PLUS TMP/SMX PLUS Ciprofloxacin |
| Post-neurosurgery or penetrating head trauma | S. pneumo (if CSF leak), H. influenzae, Staphylococci (MRSA, CoNS), Gram-negatives | Vancomycin PLUS EITHER Cefepime OR Meropenem | Vancomycin PLUS Ciprofloxacin |
| Infected Shunt | S. aureus, CoNS, P. acnes, gram-negatives (rare) | Vancomycin PLUS Cefepime | Vancomycin PLUS Ciprofloxacin |
*Use of Dexamethasone
● Addition of dexamethasone is recommended in all adult patients with suspected pneumococcal meningitis (most community-acquired adult patients)
● Dose: 0.15 mg/kg IV q6h for 2-4 days
● The first dose must be administered 10-20 minutes before or concomitant with the first dose of antibiotics.
● Administration of antibiotics should not be delayed to give dexamethasone.
● Dexamethasone should not be given to patients who have already started antibiotics.
● Continue dexamethasone only if the CSF gram stain shows Gram-positive diplococci or if blood or CSF grows S. pneumoniae.
● Consider adding rifampin for suspected S. pneumoniae, pending susceptibilities, if dexamethasone is used. If S. pneumoniae is beta-lactam susceptible, rifampin may be discontinued.
Pathogen-Specific Therapy
| Pathogens | Preferred | Alternatives for serious PCN allergy (ID consult advised) |
| S. pneumo PCN MIC ≤ 0.06 AND/OR Ceftriaxone MIC < 0.5 | Penicillin OR Ceftriaxone | Vancomycin OR Chloramphenicol, consider PCN desensitization |
| S. pneumo PCN MIC >0.1 - 1 AND Ceftriaxone MIC < 1 (ID consult advised) | Ceftriaxone | Linezolid |
| S. pneumo PCN MIC >1 AND/OR Ceftriaxone MIC ≥ 1 (ID consult advised) | Ceftriaxone PLUS Vancomycin PLUS Rifampin | Linezolid |
| N. meningitidis PCN susceptible (MIC < 0.1) | Penicillin* OR Ceftriaxone | Ciprofloxacin OR Chloramphenicol, consider PCN desensitization |
| H. influenzae Non-beta lactamase producer | Ampicillin OR Ceftriaxone | Chloramphenicol OR Ciprofloxacin, consider PCN desensitization |
| H. influenzae Beta-lactamase producer | Ceftriaxone | Chloramphenicol OR Ciprofloxacin, consider PCN desensitization |
| Listeria | Ampicillin ± Gentamicin | TMP/SMX |
| P. aeruginosa (ID consult advised) | Cefepime OR Meropenem | Any 2 of the following: Ciprofloxacin, Gentamicin, Aztreonam |
| E. coli and other Enterobacteriaceae | Ceftriaxone ± Ciprofloxacin OR Meropenem | Aztreonam OR Ciprofloxacin OR TMP/SMX |
| S. aureus - methicillin-susceptible (MSSA) | Oxacillin | Vancomycin |
| S. aureus - methicillin-resistant (MRSA) | Vancomycin OR Linezolid | |
| Coagulase-negative staphylococci if oxacillin MIC ≤ 0.25 | Oxacillin | Vancomycin |
| Coagulase-negative staphylcocci if oxacillin MIC > 0.25 | Vancomycin OR Linezolid | |
| Enterococcus | Ampicillin OR Vancomycin PLUS Gentamicin | Vancomycin PLUS Gentamicin, Linezolid |
Recommended Doses of Select Antimicrobial Agents for Treatment of Meningitis in Adults with Normal Renal and Hepatic Function
| Antimicrobial Agent | Dose |
| Ampicillin | 2 g q4h |
| Aztreonam | 2 g q6h |
| Cefepime | 2 g q8h |
| Ceftriaxone | 2 g q12h |
| Chloramphenicol | 1000-1500 mg q6h |
| Ciprofloxacin | 400 mg q8h |
| Meropenem | 2 g q8h |
| Metronidazole | 500 mg q6h |
| Oxacillin | 2g q4h |
| Penicillin G | 20-24 million units per day as continuous infusion |
| Rifampin | 600 mg q24h |
| TMP/SMX | 15-20 mg/kg/24h divided q6-12h |
| Vancomycin | Load with 25-35 mg/kg, then 15-20 mg/kg q8-12h (goal trough 15-20 mcg/mL) |
Indications for head CT prior to LP (do NOT delay initiation of antimicrobial therapy for CT)
● History of CNS diseases (mass lesions, CVA)
● New-onset seizure (≤ 1 week)
● Papilledema
● Altered consciousness
● Focal neurologic deficit
Duration
● STOP treatment if LP culture obtained prior to antibiotic therapy is negative at 48 hours OR no PMNs on cell count
● S. pneumoniae: 10-14 days
● N. meningiditis: 7 days
● Listeria: 21 days
● H. influenzae: 7 days
● Gram-negative bacilli: 21 days
Adjunctive therapy
● Consider intracranial pressure monitoring in patients with impaired mental status.
Encephalitis
● Herpes viruses (HSV, VZV) remain the predominant cause of treatable encephalitis.● CSF PCRs are rapid diagnostic tests and appear quite sensitive and specific.
● Have a low threshhold to treat if suspected, as untreated mortality exceeds 70%
● Treatment: Acyclovir 10 mg/kg IV q8h for 14-21 days
Brain Abscess
● Empiric treatment is guided by suspected source and underlying condition.● While therapy should be adjusted based on culture results, anaerobic coverage should ALWAYS continue even if none are grown.
| Source/Condition | Pathogens | Preferred (see dosing section above) | Alternative for serious PCN allergy (Infectious Disease consult advised) |
| Unknown | S. aureus, Streptococci, Gram-negatives, Anaerobes | Vancomycin PLUS Ceftriaxone PLUS Metronidazole | Vancomycin PLUS Ciprofloxacin PLUS Metronidazole |
| Sinusitis | Streptococci (including S. pneumoniae), Anaerobes | [Penicillin OR Ceftriaxone] PLUS Metronidazole | Vancomycin PLUS Metronidazole |
| Chronic Otitis / Mastoiditis | Gram-negatives, Streptococci, Anaerobes | Cefepime PLUS Metronidazole | Vancomycin PLUS Aztreonam PLUS Metronidazole |
| Post-neurosurgery | Staphylococci, Gram-negatives | Vancomycin PLUS Cefepime | Vancomycin PLUS Ciprofloxacin |
| Cyanotic heart disease | Streptococci (esp. S. viridans) | Penicillin OR Ceftriaxone | Vancomycin |
Diagnosis
● Culture of cerebrospinal fluid remains the mainstay of diagnosis. Clinical symptoms may be mild and/or non-specific, and CSF chemistries and WBC counts may be normal.
Empiric Therapy (see dosing section for CSF dosing)
● Vancomycin PLUS Cefepime
OR
● PCN Allergy: Vancomycin PLUS Ciprofloxacin
TREATMENT NOTES
● Infectious Diseases consult recommended for assistance with timing of shunt replacement and duration of therapy.
● Removal of all components of the infected shunt with external ventricular drainage or intermittent ventricular taps in combination with the appropriate intravenous antibiotic therapy leads to the highest effective cure rates. Success rates are substantially lower when the infected shunt components are not removed.
● Intraventricular antibiotics are occasionally used, particularly when there has been no improvement after 48 hours, for refractory cases, or cases in which shunt removal is not possible. Intraventricular injection should be administered only by experienced practitioners, such as the Neurocritical care service.
References
IDSA Guidelines for the Management of Bacterial Meningitis: Clin Infect Dis 2004;39:1267.
Dexamethasone in adults with bacterial meningitis: N Eng J Med 2002;347:1549.
Therapy in cerebrospinal fluid shunt infection. Neurosurgery 1980;7:459.
These guidelines are intended to provide assistance in selection of appropriate antimicrobial therapy for specific organisms. This is not intended to be a comprehensive list of all bacteria, only commonly-isolated ones. Some of the organisms listed, such as Proprionibacterium acnes and Bacillus spp, may represent contaminating organisms when isolated from blood culture.
Treatment should be guided by susceptibility testing, when available. The recommendations given below are meant to serve as guidelines. They should NOT supplant clinical judgment or Infectious Diseases consultation.
Note that antimicrobials may have differing pharmacokinetic profiles, such as CSF penetration or urinary concentration. Therefore depending on the clinical syndrome and site of infection, not all listed antimicrobials are appropriate for the listed organisms. Please feel free to contact the Antimicrobial Stewardship Program hotline at 310-267-7567 with questions.
| Organisms | First-line treatment* | Alternate treatment* |
| Acinetobacter Multli-drug resistant | meropenem (not ertapenem) consult ID | pip/tazo, ampicillin-sulbactam, cefepime, fluoroquinolone, amikacin, doxycycline, TMP/SMX. |
| Bacillus spp (not B. anthracis) | vancomycin | clindamycin, ertapenem, fluoroquinolone |
| Bacteroides fragilis | metronidazole | ertapenem, piperacillin/tazobactam, clindamycin, cefoxitin, tigecycline |
| Bordatella pertussis | macrolide | TMP/SMX |
| Campylobacter jejuni | erythromycin, azithromycin | doxycycline, flouroquinolone, gentamicin |
| Chlamydophila pneumoniae | doxycycline, macrolide | fluoroquinolone, tigecycline |
| Citrobacter freundii | ertapenem | fluoroquinolone, aminoglycoside, TMP/SMX, piperacillin/tazobactam, cefepime, tigecycline, aztreonam |
| Clostridium difficile | metronidazole | vancomycin (oral) |
| Clostridium perfringens | penicillin | metronidazole, clindamycin, piperacillin/tazobactam, ertapenem |
| Corynebacterium Group JK | vancomycin | linezolid, daptomycin, dalfopristin/quinupristin |
| Enterobacter | ertapenem or meropenem | fluoroquinolone, TMP/SMX, cefepime, pip/tazo, aminoglycoside, tigecycline, aztreonam |
| Enterococcus Ampicillin-sensitive Ampicillin-resistant, vancomycin-sensitive VRE Add gentamicin or streptomycin when cidal activity is required (eg for endocarditis) and agents are susceptible for synergy | ampicillin, amoxicillin, penicillin vancomycin linezolid | vancomycin, linezolid, piperacillin/tazobactam, dalfopristin/quinupristin (E faecium only), daptomycin, tigecycline linezolid, daptomycin, dalfopristin/quinupristin (E faecium only) daptomycin, dalfopristin/quinupristin (E faecium only), tigecycline |
| Escherichia coli ESBL-producing strains | ceftriaxone, cefazolin, cefepime ertapenem | fluoroquinolone, aminoglycoside, pip/tazo, TMP/SMX, tigecycline, aztreonam |
| Fusobacterium sp | penicillin | metronidazole, clindamycin, ampicillin/sulbactam, carbapenem |
| Haemophilus influenzae (serious infections only) | ceftriaxone | fluoroquinolone, TMP/SMX, azithromycin, clarithromycin, pip/tazo, doxycycline, cephalosporins |
| Klebsiella pneumonia ESBL-producing strains carbapenem-resistant strains | ceftriaxone, cefepime ertapenem consult ID | fluoroquinlone, aminoglycoside, TMP/SMX, pip/tazo, carbapenem, tigecycline |
| Legionella | levofloxacin, azithromycin +/- rifampin | clarithromycin, doxycycline, TMP/SMX, any of these three +/- rifampin |
| Listeria monocytogenes | ampicillin or penicillin +/- gentamicin Never cephalosporins | TMP/SMX |
| Moraxella catarrhalis | 2nd or 3rd-gen cephalosporin | fluoroquinolone, azithromycin, clarithromycin, TMP/SMX, cefepime, pip/tazo |
| Morganella morganii | cefepime, fluoroquinolone | ertapenem, pip/tazo, aminoglycoside, TMP/SMX, aztreonam |
| Mycoplasma pneumoniae | azithromycin | doxycycline, fluoroquinolone |
| N gonorrhoeae | Check with and report to LA County ceftriaxone + azithromycin | cefixime + azithromycin or doxycycline |
| N meningitidis (see section on CNS infections) Prophylaxis (with Hospital Epidmeology input) | penicillin, ceftriaxone | ampicillin, chloramphenicol ciprofloxacin, rifampin |
| Pasteurella multocida | penicillin, ampicillin, amoxicillin, amox/clav (if polymicrobial) | Doxycycline, ceftriaxone, TMP/SMX, amp/sulbactam, pip/tazo |
| Propionibacterium acnes | Penicillin | clindamycin, doxycycline, ertapenem |
| Proteus sp P mirabilis P vulgaris | ampicillin, amoxicillin, cephalosporin ertapenem | fluoroquinolone, aminoglycoside, TMP/SMX, pip/tazo, ertapenem fluoroquinolone, aminoglycoside, TMP/SMX, pip/tazo, ceftriaxone, cefepime, aztreonam |
| Providencia | ertapenem | fluoroquinolone, aminoglycoside, TMP/SMX, pip/tazo, ceftriaxone, cefepime, aztreonam |
| Pseudomonas aeruginosa See section on “double-coverage” of gram-negatives Multi-drug resistant | Cefepime or meropenem, plus gentamicin or ciprofloxacin until susceptibilities are known Consult ID | ciprofloxacin, levofloxacin, pip/tazo |
| Serratia sp | ertapenem | fluoroquinolone, aminoglycoside, cefepime, TMP/SMX, pip/tazo, aztreonam |
| Staphylococcus sp Methicillin-S Methicillin-R (MRSA) Vancomycin-intermediate or resistant (VISA, VRSA) | oxacillin, cefazolin, dicloxacillin vancomycin Consult ID | clindamycin (if S and no inducible resistance), TMP/SMX, doxycycline, cefepime, ceftriaxone, pip/tazo, ertapenem linezolid, daptomycin, for mild to moderate infections or step-down therapy: TMP/SMX, doxycycline |
| Stenotrophomonas maltophila | TMP/SMX Typically causes colonization (e.g. airways) and no treatment needed unless isolated from a sterile site, | levofloxacin, tigecycline, doxycycline |
| Streptococcus sp S pneumoniae Penicillin-susceptible Penicillin-resistant Beta Streptococci Viridans group | penicillin, amoxicillin Meningitis: vancomycin + ceftriaxone +/- rifampin Other infections: levofloxacin, vancomycin, ceftriaxone penicillin, cephalosporins penicillin, cephalosporin, for endocarditis base treatment on penicillin susceptibility testing | ceftriaxone, macrolide, clindamycin, doxycycline, fluoroquinolone linezolid, dalfopristin/quinupristin, macrolide, clindamycin, vancomycin vancomycin, levofloxacin |
| Ureaplasma | Macrolide, doxycycline |
Modified from Choice of Antibacterial Drugs. Treat Guidel Med Lett. 2007;5:33-50. Erratum in: Treat Guidel Med Lett. 2007;5:58.
Diagnosis
● If there is more than minimal erythema or ANY purulence at the exit site, the catheter is likely infected. It should be removed and replaced at a different site.
● Two sets of blood cultures should be drawn with AT LEAST one (and preferably both) from peripheral sites. Blood cultures drawn through non-tunneled catheters are more likely to yield contaminants. One set of cultures may be drawn through a catheter if it is tunneled.
● The utility of cultures of the catheter itself is not well defined, and should ONLY be sent when there is a clinical suspicion of infection, NOT routinely when lines are removed. They MUST be accompanied by two sets of blood cultures obtained as detailed above.
● Technique: The exit site should be cleaned with alcohol. The catheter should be grasped a few centimeters proximal to the exit site. A 5 cm segment of catheter including the intradermal segment just distal to the insertion site should be cut off with sterile scissors and placed in a sterile container.
● In instances where the blood and catheter are cultured at the same time and the blood cultures are negative but the catheter culture is positive, antibiotics are generally not recommended, even for patients with valvular heart disease or immunosuppression.
● The exception is patients whose catheter tips grow S. aureus and have negative blood cultures. These patients should receive 5–7 days of antibiotics.
● All patients should be followed closely, and repeat cultures should be sent if clincally indicated.
● When a catheter-associated BSI is associated with catheter dysfunction, consider the possibility of suppurative thrombophlebitis.
Management
● Antibiotics should generally be withheld in febrile patients with intravenous catheters and no other clear source of infection pending the results of blood cultures. Exceptions include immunosuppressed or critically ill patients, patients with valve replacement or other hardware in place, or instances where there is purulence at the catheter site.
Empiric treatment - immunosuppressed or critically ill patients
● Vancomycin (see dosing section) AND
● Cefepime 1 g IV q8h OR Piperacillin/tazobactam 4.5 g IV q6h] ± Gentamicin (see dosing section)
OR
● PCN allergy: Ciprofloxacin 400 mg IV q8h ± Gentamicin (see dosing section)
Empiric treatment - gram-positive cocci in clusters in 2 or more sets of blood cultures
● Vancomycin (see dosing section)
Treatment Notes:
● Microbiology: Most common pathogens: coagulase-negative staphylococci, Enterococci, S. aureus, gram-negative bacilli, Candida
● Catheter salvage:
○ Catheter removal is STRONGLY recommend for infections with S. aureus, yeast, and Pseudomonas, as the chance of catheter salvage is low and the risks of ongoing infection can be high.
○ Infected catheters should never be exchanged over a wire.
○ Catheters associated with tunnel infections CANNOT be salvaged and must be removed.
○ Catheter salvage can be considered in CLABSI caused by coagulase-negative staphylococci if the patient is clinically stable.
○ When catheter salvage is attempted, antibiotics should be given through the infected line.
○ Duration of treatment for catheter salvage is similar to duration of treatment when the catheter is removed.
○ Antibiotic lock therapy, in which an antibiotic is infused into the catheter and left in place, can be considered in the treatment of tunneled catheter infections due to less virulent pathogens such as CoNS. Infectious Diseases consult is advised.
Coagulase-negative staphylococci (CoNS)
NOTE: Single positive cultures of CoNS should NOT be treated unless they are confirmed by follow-up cultures, the patient is immunosuppressed and/or critically ill, or the patient has implanted hardware such as prosthetic valves. In these cases, treatment can be started but repeat cultures should be sent PRIOR to initiation of therapy to confirm the diagnosis
● Vancomycin (see dosing section)
Change to
● Oxacillin 12g/24h if susceptible (preferred to vancomycin)
Duration:
● 5-7 days if catheter removed (preferred)
● 10-14 days if catheter salvage attempted
Staphylococcus aureus
● Vancomycin (see dosing section)Change to
● Oxacillin 12g/24h if susceptible (preferred over vancomycin if susceptible)
OR
● Non-anaphylactic PCN allergy: Cefazolin 2g IV q8h
OR
● Anaphylactic PCN allergy or MRSA: Vancomycin (see dosing section)
Treatment Notes:
● Remove central lines. Relapse rates are unacceptably high with line retention.
● Vancomycin is inferior to oxacillin or cefazolin for treatment of MSSA. Do not choose vancomycin solely due to convenience of dosing (such as in dialysis patients).
● All patients with S. aureus bacteremia should have an echocardiogram to rule out endocarditis. Clinical suspicion and physical exam findings do not correlate with echocardiographic findings of endocarditis in S. aureus bacteremia (Fowler JACC1997)
● Transthoracic echo (TTE) is acceptable ONLY if the study can adequately view the left-sided valves; most experts recommend transesophageal echo (TEE) in all patients with S. aureus bacteremia.
● “Valve thickening, cannot rule out endocarditis” should not be interpreted as meeting Duke criteria for a vegetation. Such patients should not receive empiric treatment for endocarditis without other compelling evidence.
● 14 days is the minimum duration of therapy for S. aureus bacteremia and should only be considered if endocarditis or other metastatic infection have been ruled out. Treatment must be parenteral.
● Linezolid should not be used to treat S. aureus bacteremia as monotherapy.
Enterococcus faecalis NOTE: Can be contaminants. Draw repeat cultures to confirm before starting treatment. 99% of E. faecalis isolates at UCLA are susceptble to Ampicillin, which should be used unless the patient has a PCN allergy.
● Ampicillin 2 g IV q4h ± Gentamicin 1 mg/kg IV q8h (see treatment notes below)
OR
● PCN allergy: Vancomycin (see dosing section) ± Gentamicin 1 mg/kg IV q8h (see treatment notes below)
Duration: 10-14 days
Enterococcus faecium NOTE: Can be contaminants. Draw repeat cultures to confirm before starting treatment. The majority (77%) of E. faecium blood isolates at UCLA are resistant to vancomycin. If the isolate happens to be susceptible to ampicillin or vancomycin, these agents should be used preferentially at the doses listed above for E. faecalis bacteremia.
● Linezolid 600 mg IV/PO q12h
OR
● Quinupristin/dalfopristin 7.5 mg/kg q8H
Treatment Notes
● Consider echocardiogram if there is persistent bacteremia >3 days on appropriate antibiotics.
● Do not use gentamicin if the lab reports no synergy with gentamicin; doing so increases the risk of nephrotoxicity without clinical benefit.
● If synergy is present, gentamicin must be added to ampicillin or vancomycin for the treatment of endocarditis; however the addition of gentamicin does not appear to change outcomes in CLABSI due to Enterococcus in the absence of endocarditis if the catheter has been removed.
● Do not use gentamicin with linezolid or quinupristin/dalfopristin given the lack of supportive evidence for synergy.
● Enterococcal endocarditis should not be treated with monotherapy. Infectious Disease consultation is advised for all cases of Enterococcal endocarditis.
Gram-negative bacilli
● Cefepime 1 g IV q8h
OR
● Piperacillin/tazobactam 4.5 g IV q6h
OR
● PCN allergy: Ciprofloxacin 400 mg IV q8h
NOTE: These are anti-pseudomonal doses. Lower the doses if Pseudomonas is NOT recovered and organisms are not susceptible to agents with a narrower spectrum of activity (Piperacillin/tazobactam 3.375 g IV q6h, or Cefepime 1 g IV q12h, or ciprofloxacin 400 mg IV q12h).
Duration: 10-14 days
Treatment Notes
● Catheters are less commonly the source of the infection; however, most advocate catheter removal if the catheter is the source
● Gram-negative endocarditis is extremely rare. Routine echocardiography is not advised unless there is high clinical suspicion of endocarditis.
Pulmonary Infections CAP HAP VAP Flu TB
The two key decisions in initial empiric therapy are whether the patient has risk factors for healthcare-associated pneumonia, in which case the antibiotic guidelines for adult healthcare-associated pneumonia must be used. The second key factor that must be considered is the immune status of the patient. Additional factors that must be considered are the treatment site for the patient, the presence of modifying factors, and the presence of risk factors for Pseudomonas and CA-MRSA. Infectious Diseases consultation should be considered for any patients who are immunocompromised or at risk for resistant pathogens.
If the patient has any of the following characteristics, see the section for Healthcare-Associated Pneumonia Empiric Therapy:
● Hospitalization for 2 d or more in the preceding 90 d
● Residence in a nursing home or a long-term care facility
● Family member with multidrug-resistant pathogen
● Immunosuppressive disease and/or therapy
● Home wound care
● Home infusion therapy
● Chronic hemodialysis
● Antimicrobial therapy within prior 90 d
Community-acquired pneumonia in hospitalized patients
These guidelines are to be used in adult immunocompetent patients only. An Infectious Diseases consult is recommended when dealing with complicated patients or immunocompromised patients. All dosages are based on normal renal and hepatic function.
TREATMENT
Empiric Treatment - patient NOT in the ICU
● Ceftriaxone 1 gm IV q24h PLUS EITHER azithromycin 500 mg PO/IV once daily OR doxycycline 100 mg PO twice daily
OR
● Levofloxacin 750 mg PO/IV q24h x 5 days
In non-critically ill patients, switch to oral agents as soon as patient is clinically improving and eating. IV therapy does not need to be continued until discharge. It is not necessary to start all CAP patients on IV therapy if they can tolerate oral therapy. See Table on Empiric Step-Down Therapy below.
Empiric Treatment - patient in the ICU
Not at risk for infection with Pseudomonas (see risks below)
● Ceftriaxone 1-2 g IV q24h PLUS EITHER azithromycin 500 mg IV q24h OR levofloxacin 750 mg IV q24h
OR
● Severe penicillin allergy: levofloxacin 750 mg IV q24h PLUS aztreonam 2 g IV q8h
At risk for infection with Pseudomonas (see risks below)
● Piperacillin/tazobactam 4.5 g IV q6h
OR
● Cefepime 1-2 g IV q8h (preferred regimen if S. pneumoniae is also considered likely)
OR
● Meropenem 1 gm IV q8h (only if known to be colonized with ESBL organism or multidrug resistant pathogen such as Pseudomonas or Acinetobacter)
OR
● Severe penicillin allergy: aztreonam 2 g IV q8h
PLUS
● Levofloxacin 750 mg IV q24h OR gentamicin 7 mg/kg/dose IV daily
PLUS
● Azithromycin 500 mg IV (IV for the first 24 hours, patient can be converted to PO after 24 hours)
● Narrow coverage (ceftriaxone + azithromycin) OR levofloxacin if Pseudomonas is not present on culture at 48 hours.
● The benefits of combination therapy in the treatment of Pseudomonas are not well-documented; if it is desired, then consider giving it only for the first 5 days of therapy. Please see the section on “double coverage of Gram-negative bacterial infections.”
● NOTE: It is a core measure requirement that all ICU patients with pneumonia initially receive IV therapy for the first 24 hours. In stable patients, conversion to PO therapy on day #2 is acceptable, if appropriate.
Risks for Pseudomonas
● Prolonged hospital or long-term care facility stay (>5 days)
● Structural disease of lung (e.g., CF, bronchiectasis)
● Steroid Rx (>10 mg prednisone / day)
● Broad-spectrum antibiotics for >7 days in the past 1 month
● AIDS, especially CD4 < 50/mL
● Neutropenia (ANC <500/dL)
Other causes of pneumonia
● Suspected aspiration: Empiric coverage for aspiration is justified only in classic aspiration syndromes suggested by loss of consciousness (e.g. overdose, seizure) PLUS gingival disease or esophageal motility disorder. Ceftriaxone and Cefepime have adequate activity against most oral anaerobes. For classic aspiration, clindamycin 600 mg IV q8h or metronidazole 500 mg IV q8h can be added to regimens not containing anaerobic coverage. Piperacillin/tazobactam provides excellent anaerobic coverage and additional antibiotics are unnecessary. Anaerobic coverage should be provided when imaging findings (CXR or CT) suggest lung abscess or empyema. Antibiotic treatment of patients who develop fever, leukocytosis, and infiltrates in the first 48h after an aspiration is likely UNNECESSARY since most aspiration pneumonias are chemical and antibiotic treatment may only select for more resistant organisms.
● Community-acquired MRSA: Necrotizing pneumonia with cavitation in absence of risk factors for cavitation listed above is concerning for CA-MRSA pneumonia, particularly if associated with a preceding or concomitant influenza-like illness. In these cases, vancomycin 15 mg/kg IV q12h (target vancomycin trough levels: 15-20 mg/L) or linezolid 600 mg IV/PO q12h can be added while awaiting culture data. Infectious Diseases consult is strongly recommended. Use of linezolid monotherapy for MRSA bacteremia, even if associated with a pulmonary source, is not recommended. In the absence of necrotizing pneumonia with cavitation, empiric coverage for CA-MRSA can be deferred until sputum and blood culture results return given their high diagnostic yield for CA-MRSA.
Pathogen-specific treatment and duration
Susceptibility results should be utilized when choosing pathogen-specific therapy.
● Streptococcus pneumoniae: IV: penicillin G OR ceftriaxone; PO: amoxicillin OR cefpodoxime OR azithromycin. Treatment for 5-10 days based on clinical stability. Levofloxacin should not be used routinely as step-down therapy for pneumococcal pneumonia if the organism is susceptible to beta-lactams.
● Legionella pneumophila: IV/PO azithromycin for 7-10 days OR levofloxacin for 10-21 days.
● Haemophilus influenzae: doxycycline OR amoxicillin/clavulanate OR ceftriaxone are preferred. Other options include cefpodoxime or levofloxacin.
Empiric step-down therapy
Broad-spectrum empiric antibiotic therapy must be accompanied by a commitment to choose pathogen-specific therapy once the culture and susceptibility results are known, which is usually within 48-72 hours. Clinical improvement generally becomes apparent after the first 48-72 hours of therapy, and therefore, the selected antimicrobial regimen should not be changed during this time unless progressive deterioration is noted or initial microbiologic studies so dictate.
In the absence of positive cultures, oral options may be selected based on initial regimen:
| Initial | Step-down (preferred) | Step-down (alternate) |
| Ceftriaxone PLUS azithromycin | Azithromycin | Doxycycline |
| Levofloxacin IV | Levofloxacin PO | Azithromycin OR doxycycline |
Doses of oral agents
| Oral Agent | Dose | Duration (days)* |
| Amoxicillin | 1 g PO TID | 5-10 |
| Azithromycin | 500 mg PO daily | 5 |
| Cefpodoxime | 200 mg PO BID | 5-10 |
| Doxycycline | 100 mg PO BID | 5-10 |
| Levofloxacin | 750 mg PO daily | 5 |
*Treat for a minimum of 5 days (include therapy before oral switch). Therapy can be stopped after the patient is afebrile for 48-72 hours and has no more than one of the following signs and symptoms: HR > 100 bpm, RR > 24 breaths/min, BP < 90 mmHg, O2 sat < 90%, altered mental status. Therapy > 5 days without a clinical reason should be avoided.
TREATMENT NOTES
Diagnosis
● Immunocompetent patients MUST have an infiltrate on chest radiograph to meet diagnostic criteria for pneumonia.
● Sputum and blood cultures should be sent on all patients admitted to the hospital BEFORE antibiotics are given.
● Therapy should not be delayed if a sputum culture cannot be obtained.
● The Legionella urine antigen is the test of choice for diagnosing legionella infection. However, this test detects only L. pneumophila serogroup 1, which is responsible for ~70-80% of infections. The test is sent to a referral laboratory with ~6 day turn-around time.
● HIV test in all patients, but especially if age < 55, severe CAP, homeless, or other risk factors.
| Indication | Blood Culture | Sputum Culture | Legionella Urinary Antigen | Other |
| ICU admission | X | X | X | Xa |
| Cavitary infiltrates | X | X | X | Xb |
| Active alcoholic | X | X | X | |
| Asplenia | X | |||
| Travel within 2 weeks prior | X | Xc | ||
| Positive Legionella urinary antigen result | Xd | NA | ||
| Pleural effusion | X | X | X | Xe |
aEndotracheal aspirate or bronchoalveolar lavage if intubated.
bFungal and mycobacterial (tuberculosis) cultures and stains. Consider Coccidioides if epidemiologic risk. Consider echocardiogram if septic emboli are a concern.
cLegionella, Influenza, Coccidioides or other endemic mycoses, Hantavirus, Burkholderia pseudomallei, avian influenza, and SARS are all potential considerations depending on the destination and season.
dSpecial media for Legionella
eThoracentesis and pleural fluid cultures if loculated or effusions greater than 1cm on lateral decubitus film.
Management
● The decision to admit a patient should be based on clinical judgment with consideration of age, severity of illness, co-morbid conditions, and factors that may compromise the safety of home care.
● The nonresponding patient should be evaluated for noninfectious mimics of pneumonia, unsuspected or drug-resistant organisms, extrapulmonary sites of infection, and complications of pneumonia and its therapy. If a noninfectious etiology is identified, antibiotics should be discontinued.
● A CURB-65 score may be calculated to assist in patient disposition decisions.
● If BUN level is unavailable, the CRB-65 score can be calculated instead and appears to perform comparably to CURB-65 score.
CURB-65 Scoring System:
| Patient Characteristic | Points Assigned |
| Confusion (based on specific mental test or disorientation to person, place, or time) | 1 |
| BUN level > 20 mg/dL | 1 |
| Respiratory rate ≥ 30 breaths/min | 1 |
| Low blood pressure (systolic < 90 mmHg or diastolic < 60 mmHg) | 1 |
| Age ≥ 65 years | 1 |
| Score | Recommend Site of Care |
| 0 | Outpatient |
| 1 | Outpatient |
| 2 | Inpatient |
| ≥3 | Inpatient, consider ICU |
Resolution of symptoms
● Cough and chest radiographic abnormalities may take 4-6 weeks to improve. There is NO need to extend antibiotics if the patient is doing well otherwise (e.g. afebrile and clinically improving).
● There is no need for routine follow-up chest radiograph if the patient is otherwise improving.
Other considerations
● Consider influenza during season (November through March) or in returning travelers and test and treat appropriately.
● Consider Pneumococcal and Influenza vaccines if indicated.
● Consider HIV test.
References:
IDSA/ATS Consensus Guidelines for CAP: Clin Infect Dis 2007;44:S27.
Capelastegui A, et al. Eur Respir J 2006;27:151-7
Healthcare-associated Pneumonia (NOT ventilator-associated)
Definitions
Hospital-acquired Pneumonia (HAP): Pneumonia occurring 48 hours or more after admission, which was not incubating at the time of admission.
Ventilator-associated Pneumonia (VAP): Pneumonia occurring more than 48-72 hours after endotracheal intubation.
Healthcare-associated Pneumonia (HCAP): Pneumonia within 48 hours of hospital admission in any patient who was:
● Hospitalized in an acute care hospital for two or more days within 90 days of the infection
● Resided in a nursing home or long-term care facility
● Received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection
● Attended a hospital or hemodialysis clinic.
TREATMENT
These guidelines are to be used in adult immunocomptent patients only. An Infectious Diseases consult is recommended when dealing with complicated patients or immunocompromised patients. All dosages are based on normal renal and hepatic function.
Broad-spectrum empiric antibiotic therapy must be accompanied by a commitment to de- escalate antibiotics, on the basis of serial clinical and microbiologic data, to limit the emergence of resistance in the hospital.
NOTE: If the patient is on antibiotic therapy or has recently been on antibiotic therapy, choose an agent from a different class.
Empiric treatment
No risk factors for Pseudomonas infection (see risks below)
● Ceftriaxone 1 g IV q24h
OR
● Levofloxacin 750 mg IV q24h
At risk for Pseudomonas infection (see risks below)
● Piperacillin/tazobactam 4.5 g IV q6h
OR
● Cefepime 1 g IV q8h
OR
● Meropenem 1 gm IV q8h (only if known to be colonized with ESBL organism or multidrug resistant pathogen such as Pseudomonas or Acinetobacter)
OR
● Severe penicillin allergy: levofloxacin 750 mg IV q24h
● If the patient is on immunosuppressive medications or is neutropenic, ADD azithromycin 500 mg IV/PO q24h to cover Legionella unless the patient is already on levofloxacin.
NOTE: Lower doses for piperacillin/tazobactam to 3.375 g IV q6h and cefepime to 1 g q12h if Pseudomonas is not recovered.
Risk factors for Pseudomonas infection:
● Prolonged hospital or long-term care facility stay (≥ 5 days)
● Steroid use (> 10 mg prednisone per day)
● Broad spectrum antibiotics for > 7 days in past month
● Structural lung disease
● AIDS (CD4 < 50)
● Granulocytopenia (ANC < 500)
TREATMENT NOTES
Diagnosis
● The clinical diagnosis can be made if the patient has a new radiographic infiltrate PLUS at least two of the followoing: fever >38° C, leukocytosis or leukopenia, or purulent secretions.
● Etiologic diagnosis generally requires a lower respiratory tract culture, preferably obtained before the administration of antibiotic therapy.
Microbiology
● Gram-negative rods including Enterobacteriaceae (e.g. Klebsiella, E. coli, Serratia)
● Anaerobes (rarely)
● Legionella
● S. aureus (MRSA and MSSA)
● Pseudomonas (IF risk factors are present - see above)
● Enterococci, Stenotrophomonas, and Candida species are often isolated from the sputum in hospitalized patients. In general, they should be considered to be colonizing organisms and should not be treated with antimicrobials.
Antimicrobial management of “aspiration” in the hospital
● Prophylactic antibiotics ARE NOT recommended for patients who are at increased risk for aspiration.
● Immediate treatment is indicated for patients who have small-bowel obstruction or are on acid suppression therapy given the increased risk of gastric colonization.
● Antibiotic treatment of patients who develop fever, leukocytosis, and infiltrates in the first 48h after an aspiration is likely UNNECESSARY since most aspiration pneumonias are chemical and antibiotic treatment may only select for more resistant organisms.
● Treatment IS recommended for patients who have symptoms for more than 48 hours or who are severely ill.
References:
Aspiration pneumonitis and aspiration pneumonia: N Engl J Med 2001;344(9):665.
ATS/IDSA Guidelines for HAP/VAP: AJRCCM 2005;171:388.
Ventilator-associated Pneumonia (VAP)
These guidelines are to be used in adult immunocompetent patients only. An Infectious Diseases consult is recommended when dealing with complicated patients or immunocompromised patients. All dosages are based on normal renal and hepatic function.
● Sputum cultures should be obtained prior to starting or changing antibiotics by endotracheal suction or invasive techniques such as mini-BAL. ET suction appears just as sensitive but less specific than invasive methods.
● Empiric treatment MUST be narrowed as soon as sputum culture results are known.
● Vancomycin can be STOPPED if no resistant Gram-positive organisms are identified.
● If the patient is on antibiotic therapy or has recently been on antibiotic therapy, choose an agent from a different class.
TREATMENT
● Treatment MUST be narrowed based on culture results
● Vancomycin 15 mg/kg/dose q12h (see dosing section) OR Linezolid 600 mg IV/PO q12h
PLUS
● Piperacillin/tazobactam 4.5 g IV q6h OR Cefepime 1 g IV q8h (2g IV q8h if neutropenia) OR meropenem 1 g IV q8h OR severe penicillin allergy: ciprofloxacin 400 mg IV q8h OR aztreonam 2 g IV q6h
PLUS
● Gentamicin 5-7 mg/kg IV q24h (preferred) OR ciprofloxacin 400 mg IV q8h
NOTE: These are antipseudomonal doses. LOWER the dose (piperacillin/tazobactam 3.375 g IV q6h, cefepime 1 g IV q12h) if Pseudomonas is NOT recovered
If the patient is immunocompromised, consider ADDING azithromycin 500 mg IV/PO q24h to cover Legionella unless the patient is already on levofloxacin.
Gentamicin is recommended as the second agent to broaden empiric coverage rather than fluoroquinolones because of high rates of resistance to fluoroquinolones in the institution (36% of Pseudomonas at UCLA is cipro-resistant).
Nebulized antibiotics (aminoglycosides or colistin) are not recommended for routine use due to an absence of data on their utility except in specific patient populations (e.g., cystic fibrosis). Neublized antibiotics should not be used for suppressive therapy in patients with tracheal colonization.
Antimicrobial therapy should be tailored once susceptibilities are known. Vancomycin should be stopped if resistant Gram-positive organisms (MRSA) are not recovered. Gram-negative coverage can be reduced to a single susceptible agent in most cases. The benefits of combination therapy in the treatment of Pseudomonas VAP are not well-documented; if it is desired then combination therapy should be given for the first 5 days of therapy only (see the section on “double coverage” of Gram-negative organisms).
Duration
● 7-8 days if the patient has clinical improvement, Pseudomonas may require longer treatment.
● If symptoms persist at 8 days consider: alternate sources for infection, non-infectious causes (e.g. ARDS, CHF), and bronchoscopy with quantitative cultures.
● VAP associated with S. aureus bacteremia should be treated for a minimum of 14 days.
TREATMENT NOTES
Microbiology
● Staphylococcus aureus (MRSA and MSSA), Pseudomonas aeruginosa, other Gram-negative bacilli, Legionella
● Enterococci, Stenotrophomonas, and Candida species are often isolated from the sputum in intubated patients. In general, they should be considered to be colonizing organisms and should NOT be treated with antimicrobials.
Diagnosis
● VAP is difficult to diagnose.
● Bacteria in endotracheal secretions may represent tracheal colonization and NOT infection. Not all positive sputum cultures should be treated.
● Quantitative cultures of BAL fluid can help distinguish between colonization and infection; ≥ 104 cfu/ml is considered significant growth.
Other considerations
● Tracheal colonization of Gram-negatives and S. aureus is not eradicated even though lower airways are sterilized. Thus, post-treatment cultures in the absence of clinical deterioration (fever, rising WBC, new infiltrates, worsening ventilatory status) are not recommended.
● Inadequate initial treatment of VAP is associated with higher mortality (even if treatment is changed once culture results are known).
● Efforts to reduce the duration of therapy are justified by studies of the natural history of the response to therapy. Data support the premise that most patients with VAP who receive appropriate antimicrobial therapy have a good clinical response within the first 6 days. Prolonged therapy simply leads to colonization with antibiotic resistant bacteria.
References:
ATS/IDSA Guidelines for HAP/HAV: AJRCCM 2005;171:388.
Clinical response to VAP: AJRCCM 2001;163:1371-1375.
VAP: Arch Intern Med 2000;160:1926-6.
Mini-BAL: Chest 1998;113:412-20.
CPIS score: Am Rev Respir Dis 1991;143:1121–1129.
Determining course of therapy using CPIS Score: Am J Respir Crit Care Med 2000; 162: 505, Intensive Care Med 2004; 30: 735–738.
Seasonal Influenza Diagnosis and Management
Diagnosis
● Respiratory virus testing should be considered in individuals presenting during influenza season with fever and influenza-like symptoms of myalgia, arthralgia, headache, and/or sore throat.
● Travelers to the Southern Hemisphere may acquire influenza out of season.
● Nasopharyngeal swab specimens are the preferred specimen for the purpose of respiratory virus testing.
Treatment for inpatients
● Should be considered for confirmed cases with symptoms onset in the past 48 hours.
● Consideration can be given to treating immunocompromised patients who are outside the 48 hour window, although no data exist to show significant benefit.
● Antiviral choice is dependent on the susceptibility of circulating strains which may vary from season to season (see http://www.asp.mednet.ucla.edu for updated information).
Antiviral Agents
| Medication | Adult Dosing | Side Effects | Notes |
| Oseltamivir | Treatment: 75 mg PO BID x 5d Prophylaxis: 75 mg PO daily | Common: nausea, vomiting Severe: hypersensitivity, neuropsychiatric | Dose adjustment needed for GFR <30 ml/min |
| Zanamivir | Treatment: 10 mg (2 oral inhalations) BID x 5d Prophylaxis: 10 mg (2 oral inhalations) daily | Common: diarrhea, nausea, cough, headache, and dizziness Severe: bronchospasm, hypersensitivity | Should NOT be used in patients with chronic airway diseases |
| Amantadine | Treatment/ Prophylaxis: 100 mg PO BID or 200 mg daily | Common: nervousness, anxiety, difficulty concentrating, lightheadedness, nausea Severe: hypersensitivity, neuropsychiatric | Dose adjustment needed for GFR <50 ml/min |
| Rimantadine | Treatment/ Prophylaxis: < 65 y/o 100 mg BID > 65 y/o 100 mg daily | Common: nervousness, anxiety, difficulty concentrating, lightheadedness, nausea Severe: hypersensitivity, neuropsychiatric | Dose adjustment needed for GFT <10 ml/min and severe hepatic dysfunction. |
Infection Control
● All established Occupational Health Services and Hospital Epidemiology policies should be followed by all UCLA employees.
● All individuals with suspected influenza infection should be placed on droplet precautions. When outside their room (e.g. during transport) patients should wear a mask.
● All heath care workers should receive the influenza vaccine yearly.
● Personnel with direct patient care or working in clinical areas who have not received the influenza vaccine are suggested to wear a mask when within 3 feet of a patient.
● Employees who are febrile or have flu-like symptoms during flu season are advised to stay home. If they become sick while at work, they must go to Occupational Health Services. http://ohs.uclahealth.org
● Employees who have cold symptoms, such as cough and runny nose, WITHOUT fever should wear a surgical mask during patient contact.
Tuberculosis (TB) Infection
DEFINITIONS
Acid fast bacilli (AFB): Bacteria, including Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) that are detected in clinical specimens by direct microscopy using and acid-fast stain.
● Negative AFB smear does not rule out active TB.
● Cultures may take 6 weeks to grow.
Tuberculin Skin Test (TST): Intradermal injection of purified protein derivative (PPD) and measurement of induration diameter in 48-72 hours for diagnosis of latest TB infection (also positive in most active TB cases).
Criteria for a positive test are:
○ ≥ 5mm - high risk of developing active TB (e.g. HIV, close contact of TB case, immunocompromised)
○ ≥ 10mm - other risk factors for TB infection (healthcare worker, IV drug use, diabetes)
○ ≥ 15mm - no risk factors for TB
QuantiFERON Gold: Immunoserology test that measures T-cell release of interferon-gamma (IFN-gamma) following stimulation by antigens unique to M. tuberculosisis. The results are reported as positive, negative, or indeterminate. QuantiFERON Gold results are NOT affected by prior BCG vaccination and thus are useful in diagnosing latent TB infection in patients with a history of BCG vaccination. As with the TST, results of this test should be interpreted with other relevant clinical information such as age, BCG status, history of contact with active TB, and risk factors that increase the risk of progression to active disease such as immunosuppression.
Latent TB Infection (LTBI): Previous infection with TB that has been contained by the host immune response.
● Patients may have a positive TST or suggestive radiographic findings such as calcified granulomata or minimal apical scarring, but do not have symptoms of active TB disease.
● Not infectious and does not require isolation.
Active TB disease: Active replication of M. tuberculosis causing pulmonary or extrapulmonary symptoms and/or signs.
● Confirmed by positive AFB smear, MTB test, or culture.
● Requires airborne isolation.
When to Suspect Active TB Disease
High-risk individuals
● Recent exposure to a person with known TB; history of a positive TST or QuantiFERON Gold; HIV infection; injection or non-injection drug use; foreign birth or residence in a region in which TB incidence is high; residents and employees of high-risk congregate settings (e.g. prisons); membership in a medically underserved, low-income population; anti-TNF alpha therapy
Clinical syndromes
● Cough of >2 week duration, with at least one additional symptom, including fever, night sweats, weight loss, or hemoptysis.
● Any unexplained respiratory illness of >2 week duration in a patient at high risk for TB.
● Any patient with HIV infection and unexplained cough and fever.
● Any patient on anti-TNF alpha therapy with unexplained fever.
● Community-acquired pneumonia which has not improved after 7 days of appropriate treatment.
● Incidental findings on chest radiograph suggestive of TB (even if symptoms are minimal or absent) in a patient at high risk for TB.
Radiographic findings
● Primary TB (often unrecognized): Can resemble CAP and involve any lobes; hilar adenopathy, pleural effusions are common; cavitation is uncommon. Findings often resolve after 1-2 months. These are common findings in patients with advanced HIV infection and TB.
● Reactivation TB: Infiltrates with or without cavitation in the upper lobes or the superior segments of the lower lobes; hilar adenopathy is variable; CT scan may have “tree-in-bud” appearance.
Diagnosis
● Patients with characteristic syndromes and radiographic findings should have expectorated sputum obtained for AFB smear and culture.
● Sensitivity of AFB smear on expectorated sputum is 50-70%; it is lower in HIV+ patients. Morning expectorated sputum, induced sputum, bronchoscopy have higher sensitivity. AFB culture of lower respiratory tract specimens is considered the gold standard.
● AFB smear and culture should be obtained regardless of chest x-ray findings in patients with high clinical suspicion, HIV infection, or other immunocompromised states. CXR is normal in approximately 10% of HIV+ patients with pulmonary TB.
TREATMENT
Active TB
● Infectious Diseases consult is strongly advised.
● Therapy should be initiated for patients with positive AFB smear and clinical findings consistent with active TB.
● Therapy should be considered for patients with negative AFB smears when suspicion of TB is high and no alternate diagnosis exists. Multiple specimens should be obtained for culture prior to initiation of treatment.
● Four drugs are necessary for the initial phase (2 months)
○ Isoniazid (INH) 300 mg* (5 mg/kg) PO daily
○ Rifampin (RIF) 600 mg* (10 mg/kg) PO daily
○ Pyrazinamide (PZA) 1000 mg (40-55 kg) OR 1500 mg (56-75 kg) OR 2000 mg* (76-90 kg) PO daily
○ Ethambutol (EMB) 800 mg (40-55 kg) OR 1200 mg (56-75 kg) OR 1600 mg * (76-90 kg) PO daily
*Max dose, regardless of weight
● Pyridoxine 25 mg PO daily is recommended to prevent INH-associated peripheral neuropathy in patients with: HIV, malnutrition, alcohol abuse, diabetes mellitus, renal failure, pregnancy, or breastfeeding.
● NB: LA County TB Control must approve ALL discharge plans for patients with active TB. Hospital Epidemiology can assist with decisions about isolation and discharge plans.
Latent TB
● Treatment of latent tuberculosis should rarely be started in the hospital and requires a clear follow-up plan and commitment from the patient and their physician.
Drug toxicity and monitoring
● INH: asymptomatic elevation in hepatic enzymes, serious and fatal hepatitis, peripheral neuropathy.
● RIF: orange discoloration of body fluids, hepatotoxicity (cholestatic), pruritis with or without rash, numerous drug interactions.
● PZA: hepatotoxicity, nongouty polyarthralgia, asymptomatic hyperuricemia, acute gouty arthritis.
● EMB: retrobulbar and peripheral neuritis, color vision.
● Monitoring: baseline hepatic panel, creatinine and CBC are recommended for all adults initiating TB treatment. Monthly hepatic panel is recommended for patients with baseline abnormalities, history of liver disease or viral hepatitis, chronic alcohol consumption, HIV, IVDU, pregnancy or immediate post-partum state, or those taking other potentially hepatotoxic medications.
● Therapy should be discontinued immediately if AST and ALT are >3 times the upper limit of normal in the presence of jaundice or hepatitis symptoms or >5 times the upper limit of normal in the absence of symptoms.
References
ATS/IDSA/CDC Guidelines for diagnosis of TB: Am J Respir Care Med 2000;161:1376.
ATS/IDSA/CDC Guidelines for treatment of TB: MMWR;52:RR-11.
Skin and Soft Tissue Infections Cellulitis Cutaneous Abscess Recurrent MRSA Diabetic Foot Surg Site Infxn Nec Fasciitis
Cellulitis Note: The most common etiology of cellulitis with purulent drainage is S. aureus, although Group A streptococci and other streptococcal species can also present in this manner.
TREATMENT
The following regimens include coverage for MSSA, community-acquired MRSA (CA-MRSA), and streptococci. Coverage for gram negative organisms is not needed except in very specific patient populations (outlined below).
Oral Regimens
● Doxycycline 100 mg PO BID PLUS Cephalexin 500 mg PO QID OR Amoxicillin 500 mg PO TID
OR
● TMP/SMX 1-2 DS tab PO BID PLUS Amoxicillin 500 mg PO TID*
OR
● Clindamycin 300 mg PO TID
*TMP/SMX and doxycycline have poor activity against Group A streptococci and should be combined with Amoxicillin or Cephalexin.
Parenteral Regimens
● Vancomycin (moderate to severe disease or nosocomial acquisition)
OR
● Clindamycin 600 mg IV q8h (mild disease)
Duration: 7-10 days. May step down to oral therapy when patient is improving.
| Type of Infection | Suspected Organisms | Recommended Treatment |
| Folliculitis | S. aureus, P aeruginosa (hot tub) | - Warm compresses - No antibiotics |
| Furuncles, carbuncles, “boils” | S. aureus, including CA-MRSA | - I&D - If fever and/or surrounding cellulitis, see “oral regimens” above |
| Abscesses | S. aureus, including CA-MRSA | I&D - If surrounding cellulitis, systemic symptoms, and/or multiple lesions, see “oral regimens” above - If gangrene, immunocompromised, extensive surrounding cellulitis, or severe systemic symptoms: -Consider surgical treatment -Vancomycin |
| Impetigo | S. aureus, including CA-MRSA, S. pyogenes | - Warm water soak - Oral therapy (see regimens above) |
| Erysipelas (characterized by lesions that are raised above the level of surrounding skin, with a clear demarcation between involved and uninvolved tissue) | S. pyogenes, rarely S. aureus, or S. agalactiae | - PCN VK 250-500 mg PO QID - Clindamycin 300 mg PO/600 mg IV TID - If MRSA, add TMP/SMX DS BID |
| Cellulitis | S. aureus, including CA-MRSA, S. pyogenes Diabetics: mixed anaerobic and aerobic flora. Consider gram-negative organisms in immunocompromised hosts or refractory patients. Consider anaerobes and fungi in IVDU | Mild: see “oral regimens” above Moderate / severe: see “parenteral regimens” above Mild: [Amoxicillin/clavulante 875 mg PO BID OR Ciprofloxacin 500 mg PO BID] PLUS Clindamycin 300 mg PO TID Moderate-severe -Piperacillin/tazobactam 3.375 g IV q6h OR Meropenem 500 mg IV q8h. If concern for MRSA, add vancomycin -Severe PCN allergy: Ciprofloxacin + Clindamycin OR Aztreonam + Clindamycin. If concern for MRSA, use vancomycin instead of clindamycin and add anaerobic coverage with metronidazole. |
TREATMENT NOTES
Microbiology
● S. aureus and Streptococci (especially Group A)
● Rare causes of cellulitis are discussed below
Management
● Always elevate the affected extremity. Treatment failure is more commonly due to failure to elevate than failure of antibiotics.
● Improvement of erythema can take days, especially in patients with venous stasis or lymphedema, because dead bacteria in the skin continue to induce inflammation.
● The microbiology laboratory routinely tests S. aureus isolates for inducible Clindamycin resistance and this testing is reflected in the reported susceptibility data. If no culture data to guide therapy and high risk or suspicion of CA-MRSA or failure to improve on clindamycin, change clindamycin to alternate active agent such as bactrim or doxycycline.
● Resistance to fluoroquinolones in S. aureus is common and develops quickly. The vast majority of MRSA isolates are resistant to fluoroquinolones. Therapy with fluoroquinolones for S. aureus infections is not recommended.
● Rifampin should NEVER be used as monotherapy because resistance develops rapidly.
● There is NO EVIDENCE that linezolid or daptomycin are superior to TMP/SMX, doxycycline, or clindamycin for the management of skin and soft tissue infections. Linezolid or daptomycin should only be considered when the S. aureus isolate is resistant to other agents or the patient is intolerant of these agents.
● Elimination or prevention of interdigital tinea is important for cases of relapsing lower extremity cellulitis.
● Specialty referral should be considered in cases of lymphedema, refractory tinea pedis, chronic dermopathies, venous insufficiency, or post-surgical cellulitis.
Other causes of cellulitis in select patient populations
● With bullae, vesicles, and ulcers after exposure to seawater or raw oysters, consider Vibrio vulnificus, especially in patients with chronic liver disease. Rare, but rapidly fatal if untreated. Treat with ceftriaxone 1 g IV q24h PLUS doxycycline 100 mg PO BID.
● Neutropenic, solid organ transplant, and cirrhotic patients may have cellulitis due to gram-negative organisms. Consider expanding coverage in these cases. Gram-negative cellulitis is exceedingly rare in other patient populations and routine gram-negative coverage is unnecessary.
● If an eschar is present, consider angioinvasive organisms (Pseudomonas, aspergillosis, mold). Infectious Diseases consult is advised.
● Animal and human bites: Pasteurella multocida should be covered for cat and dog bites. Treat with Amoxicillin/clavulanate 875 mg PO BID OR Ampicillin/sulbactam 1.5-3 g IV q6h. If PCN allergy: Ciprofloxacin 500 mg PO / 400 mg IV q24h PLUS Clindamycin 300 mg PO TID/600 mg IV q8h. Remember to consider tetanus booster and/or rabies vaccination.
Cutaneous Abscess ● Incision and drainage (I&D) is the primary treatment for a cutaneous abscess.
● Lesions that appear superficial can often have associated abscess formation that is not clearly appreciated without debridement of the wound or, on occasion, additional imaging.
● At the time of I&D, a sample should be obtained for culture and sensitivity testing. A superficial wound swab of purulent drainage prior to I&D is of limited utility.
● Antibiotics are an adjunct to I&D in the management of uncomplicated skin abscesses caused by CA-MRSA.
● Indications for antimicrobial therapy in patients with cutaneous abscesses:
○ Severe or rapidly progressive infections
○ The presence of extensive associated cellulitis
○ Signs and symptoms of systemic illness
○ Diabetes or other immune suppression (e.g., solid organ transplant)
○ Advanced age
○ Location of the abscess in an area where complete drainage is difficult
○ Lack of response to I&D alone.
● Antibiotic therapy should be given before I&D in patients with prosthetic heart valves or other conditions placing them at high risk for endocarditis.
TREATMENT
If antibiotic treatment is thought to be necessary due to one of the above indications, regimens are the same as for cellulitis above. If CA-MRSA is strongly suspected or confirmed, consider NOT adding Amoxicillin or Cephalexin to TMP/SMX, Doxycycline, or Clindamycin.
Recurrent MRSA Skin Infections 1. Patient education regarding approaches to personal and hand hygiene
○ Practice frequent hand hygiene with soap and water and/or alcohol-based hand gels, especially after touching infected skin or wound bandages.
○ Cover draining wounds with clean, dry bandages.
○ Do not share personal items (e.g. razors, used towels or clothing before washing).
○ Regular bathing.
○ Avoid shaving.
○ Launder clothing, sheets, towels in hot water.
○ Clean all personal sporting clothing/equipment.
2. Decontamination of the environment
○ Clean high-touch areas in the bathroom with a disinfectant active against S. aureus daily (e.g. Clorox bleach wipes)
3. Topical decolonization (consider if a patient has ≥ 2 episodes per year or other househould members develop infection)
○ Mupirocin applied to nares twice daily for 5 days may be considered in patients with documented evidence of MRSA nasal colonization; Mupirocin therapy should be initiated after resolution of acute infection. Mupirocin should not be used in patients who are not documented to have MRSA nasal colonization.
○ Bathing or showering with chlorhexidine (Hibiclens) or dilute bleach baths ever other day for 1 week then twice weekly; patients should be instructed not to get these substances into ears or eyes.
○ Systemic antibiotics are NOT recommended solely for decolonization.
4. Evaluation of family members
○ Intra-family transmission should be assessed and if present, all members should participate in hygiene and decolonization strategies above, starting at the same time and after the acute infection is controlled.
NOTE: Data on efficacy and durability of the decontamination and decolonization strategies described above are limited.
References:
IDSA Guidelines for Skin and Soft Tissue Infections. CID 2005; 41:1373-406
TMP/SMX for MRSA: Ann Intern Med 1992;117:390-8.
Management of CA-MRSA: http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.
Diabetic Foot Infections TREATMENT
Treatment depends on clinical severity
| Infection Severity | Clinical Manifestations |
| Uninfected | No purulence or inflammation |
| Mild | Presence of purulence and ≥ 1 signs of inflammation* and cellulitis (if present) ≤ 2 cm around ulcer limited to skin or superficial subcutaneous tissue |
| Moderate | Same as mild PLUS ≥ 1 of the following: > 2 cm of cellulitis, lymphangitic streaking, spread beneath the superficial fascia, deep tissue abscess, gangrene, involvement of muscle, tendon, joint, or bone. |
| Severe | Any of the above PLUS systemic toxicity or metabolic instability |
*Erythema, pain, tenderness, warmth, induration
MILD INFECTIONS
Oral Regimens
● Cephalexin 500 mg PO QID
OR
● Clindamycin 300 mg PO TID (covers MRSA)
OR
● Amoxicillin/clavulanate 875 mg PO BID
Parenteral Regimens
● Clindamycin 600 mg IV q8h (covers CA-MRSA if no inducible Clindamycin resistance)
OR
● Cefazolin 1 g IV q8h
MODERATE INFECTIONS
● Ertapenem 1g IV q24h
OR
● Ciprofloxacin 500 mg PO BID / 400 mg IV q12h PLUS EITHER Clindamycin 600 mg IV q8h/300 mg PO TID OR Metronidazole 500 mg IV/PO TID
● Avoid fluoroquinolones in patients who were on them as outpatients.
● If patient at risk for MRSA, add Vancomycin to regimens that do not include Clindamycin (see dosing section)
Risk factors for MRSA
● History of colonization or infection with MRSA
● Recent (within 3 months) or current prolonged hospitalization > 2 weeks
● Transfer from a nursing home or subacute facility
● Injection drug use
SEVERE INFECTIONS
● Pipercillin/tazobactam 4.5 g IV q6h
OR
● Ciprofloxacin 400 mg IV q12h PLUS Clindamycin 600 mg IV q8h
● BUT avoid fluoroquinolones in patients who were on them as outpatients.
If patient at risk for CA-MRSA (see above)
● Pipercillin/tazobactam 4.5 g IV q6h PLUS Vancomycin (see dosing section)
OR
● Ciprofloxacin 400 mg IV q12h PLUS Metronidazole 500 mg IV q8h PLUS Vancomycin (see dosing section)
● BUT avoid fluoroquinolones in patients who were on them as outpatients.
TREATMENT NOTES
Management
● A multidisciplinary approach to management should include wound care consultation, podiatry consult, assessment of vascular supply, vascular and/or general surgery consultation and infectious diseases consultation.
● Consider necrotizing fasciitis in patients who are severely ill.
● Antibiotic therapy should be narrowed based on culture results.
Microbiology
● Cellulitis without open wound or infected ulcer, antibiotic naive: beta-hemolytic streptococci, S. aureus
● Infected ulcer, chronic or previously treated with antibiotics: S. aureus, beta-hemolytic streptococci, Enterobacteriaceae
● Exposure to soaking, whirlpool, hot tub: usually polymicrobial, can involve Pseudomonas
● Chronic wounds with prolonged exposure to antibiotics: aerobic gram positive cocci, diptheroids, Enterobacteriaceae, other gram negative rods including Pseudomonas
● Necrosis or gangrene: mixed aerobic gram positive cocci and gram negative rods, anaerobes
Diagnosis
● Cultures of the ulcer base after debridement can help guide therapy. Avoid swabbing non-debrided ulcers or wound drainage.
● Ulcer floor should be probed carefully. If bone can be touched with a metal probe then the patient should be treated for osteomyelitis with antibiotics in addition to possible surgical debridement.
● A deep foot-space infection can be present. Consider imaging to look for deep infections.
● Putrid discharge is diagnostic for the presence of anaerobes.
● MRI is more sensitive and specific than other rmodalities for detection of soft-tissue lesions and osteomyelitis.
Duration
● Duration of treatment will depend on rapidity of response and presence of adequate blood supply or osteomyelitis.
● Likely need shorter treatment with adequate surgical intervention (7-10 days post-op) and longer for osteomyelitis.
● Change to an oral regimen when patient is stable.
Reference:
IDSA Guidelines: Clin Infect Dis 2004;39:885-910.
Surgical Site Infections (SSI) TREATMENT
Infections following clean procedures (e.g. orthopedic joint replacements, open reduction of closed fractures, vascular procedures, median sternotomy, craniotomy, breast and hernia procedures).
● Cefazolin 1 g IV q8h
OR
● PCN allergy: Clindamycin 600 mg IV q8h
OR
● Involvement of hardware: Vancomycin (see dosing section)
Exception: Saphenous vein graft harvest site infections should be treated with ertapenem 1 g IV q24h.
Infections following contaminated procedures (GI/GU procedures, oropharyngeal procedures, OB/GYN procedures)
Patients not on broad-spectrum antibiotics at time of surgery and not severely ill
● Ertapenem 1 g IV q24h
OR
● Severe PCN allergy: Ciprofloxacin 500 mg PO BID/400 mg IV q12h) PLUS Clindamycin 600 mg IV q8h
Patients on broad-spectrum antibiotics at time of surgery or severely ill
● Piperacillin/tazobactam 3.375 g IV q6h PLUS Vancomycin (see dosing section), if hardware present or MRSA suspected
OR
● PCN allergy: Vancomycin (see dosing section) PLUS Ciprofloxacin 500 mg PO BID/400 mg IV q12h) PLUS Metronidazole 500 mg PO/IV q8h
Deep fascia involvement
● Treat as necrotizing fasciitis (see dedicated section)
TREATMENT NOTES
Microbiology
● Following clean procedures (no entry of GI/GU tracts)
○ Staphylococcus aureus (including MRSA)
○ Streptococci, group A (esp with early onset, < 72 hours)
○ Coagulase-negative staphylococci
● Following clean-contaminated and contaminated procedures (entry of GI/GU tracts with or without gross contamination)
○ Organisms above
○ Gram-negative rods
○ Anaerobes (consider Clostridia spp in early-onset infections, 1-2 days)
● Generally, empiric use of Vancomycin is NOT indicated because the percentage of SSIs caused by MRSA at UCLA is low.
Risk factors for MRSA
● History of colonization or infection with MRSA
● Recent (within 3 months) or current prolonged hospitalization >2 weeks
● Transfer from a nursing home or subacute facility
● Injection drug use
Other management issues
● Many advocate that ALL infected wounds be explored both to debride and to assess the depth of involvement.
● Superficial infections may be adequately treated with debridement alone.
● Deeper infections (cellulitis, panniculitis) need adjunctive antibiotics.
● Patients with hypotension should have their wounds explored even they are unremarkable on physical exam.
Necrotizing Fasciitis (serious, deep-tissue infections) THESE ARE SURGICAL EMERGENCIES. ANTIBIOTICS ARE ONLY AN ADJUNT TO PROMPT SURGICAL DEBRIDEMENT.
Infectious Diseases should be consulted for all cases of necrotizing fasciitis.
TREATMENT (adjunct to surgery)
● Vancomycin (see dosing section) PLUS [Piperacillin/tazobactam 3.375 g IV q6h OR Cefepime 1 g IV q8h] PLUS Clindamycin 600-900 mg IV q8h
OR
● PCN allergy: Vancomycin (see dosing section) PLUS Ciprofloxacin 400 mg IV q12h PLUS Clindamycin 600-900 mg IV q8h
If confirmed beta-hemolytic streptococci:
● Penicillin G 24 Million Units as continuous infusion PLUS Clindamycin 600-900 mg IV q8h
OR
● PCN allergy: Vancomycin (see dosing section) PLUS Clindamycin 600-900 mg IV q8h
TREATMENT NOTES
Conventional nomenclature and microbiology
Pyomyositis (purulent infection of skeletal muscle, usually with abscess formation)
● S. aureus most commonly
● Clostridial myonecrosis - Clostridia spp (esp C. perfringens)
● Group A streptococcal myonecrosis
Fasciitis (infection of the subcutaneous tissue that results in progressive destruction of fascia and fat, but may spare the skin)
● Type 1 - Polymicrobial infections with anaerobes, streptococci and gram-negative rods (Fournier’s gangrene is a type 1 necrotizing fasciitis of the perineum)
● Type 2 - Group A streptococci
● Cases of fasciitis caused by community-acquired MRSA have been reported
● Case-cohort studies and case reports have suggested some benefit to treatment with intraveous immunoglobulin (IVIG) in specific circumstances (e.g., streptococcal toxic shock). However, due to the lack of randomized controlled trials, IVIG should probably be reserved for select patients. Infectious Diseases consult is advised.
Diagnosis
● Can be difficult - gas production is not universal and is generally absent in streptococcal disease.
● Can follow minor or major trauma, especially when risk factors are present.
● Maintain high index of suspicion when:
○ Patients are very ill from cellulitis (hypotension, toxic)
○ Pain out of proportion to exam findings.
○ Anesthesia over affected area
○ Risk factors such as diabetes, recent surgery, or obesity
○ Findings such as skin necrosis or bullae
○ Putrid discharge with thin, “dishwater” pus
● CT scan can help with diagnosis but if suspicion is moderate to high, surgical exploration is the preferred diagnostic test. DO NOT delay surgical intervention to obtain CT.
● Initial histopathologic findings may be of prognostic importance. A poor neutrophil response with numerous organisms seen on routine stains implies a poor prognosis.
Sepsis Note: Refer to specific sections in these guidelines for empiric treatment recommendations for specific sources of infection. Sepsis treatment should be targeted at the specific source whenever possible.
SEVERE SEPSIS
If patient has ALL 3 of the below, the patient has severe sepsis:
1. Suspected infection
2. 2 out of 4 below:
● Temperature greater than 100.4 F (38°C) or less than 96.8 F (36°C)
● Heart rate greater than 90 bpm
● Respiratory rate greater than 20 or PaCO2 less than 32 mmHg or mechanical ventilation
● WBC greater than 12,000 or less than 4,000 mm3
3. Systolic BP less than 90 mmHg after 1500 ml fluid bolus OR serum lactate ≥ 4 mmol/L
EMPIRIC TREATMENT WITH NO CLEAR SOURCE
Cultures MUST be sent to help guide therapy.
● [Pip/Tazo 4.5 g IV q6h OR Cefepime 1 g IV q8h OR Meropenem 1 g IV q8] ± Vancomycin (if at risk for MRSA) ± Gentamicin
OR
● Severe PCN allergy: [Aztreonam 2 g IV q8h OR Ciprofloxacin 400 mg IV q8h] ± Gentamicin PLUS Vancomycin
Risk factors for MRSA
● Central venous catheter in place
● Other indwelling hardware
● Known colonization with MRSA
● Recent (within 3 mos) or current prolonged hospitalization > 2 weeks
● Transfer from a nursing home or subacute facility
● Injection drug use
TREATMENT NOTES
● For patients with renal insufficiency where aminoglycosides are not desired, a beta-lactam may be combined with a fluoroquinolone IF 2 agents are needed. See section on double-coverage of gram-negative infections. Two beta-lactam agents should not be used concurrently (e.g. Pip/Tazo/Cefepime/Meropenem)
● Potential sources (e.g. pneumonia, peritonitis, central venous catheters) must be considered when selecting therapy.
● Empiric therapy is ONLY appropriate while cultures are pending (72 hours)
● Vancomycin should almost always be stopped if no resistant gram-positive organisms are recovered in cultures.
A urine culture must ALWAYS be interpreted in the context of the urinalysis and patient symptoms. If a patient has no signs of infection on urinalysis, no symptoms of infection, but a positive urine culture, the patient by definition has asymptomatic bacteriuria, or the specimen was contaminated at the time of collection with organisms present on the skin/mucous membranes. Typically, catheterized patients will become colonized within 48 hours of catheterization. Patients with chronically indwelling catheters, urinary stoma, and neobladders will almost universally have positive urine cultures. The only patient populations for which it is recommended to screen for and treat asymptomatic bacteriuria are pregnant women and patients scheduled for a genitourinary surgical procedure.
NOTES:
● The diagnosis of a UTI in inpatients can be difficult.
● Signs and symptoms, the presence of a urinary catheter, and the quality of specimen collection must be considered before initiation of treatment.
● Collection of cultures in the absence of signs and symptoms should be avoided.
● All recommendations are for empiric treatment; narrow coverage based on susceptibilities.
Management of patients without a urinary catheter
NOTE: Ciprofloxacin is not listed as an empiric treatment recommendation for inpatients with non-catheter associated UTI at UCLA due to the low rate of E. coli susceptibility (58%). Use of ciprofloxacin can be considered in patients with known-susceptible isolates or with non-lactose fermenting organisms in the urine.
| Category | Definition | Empiric Treatment |
| Asymptomatic bacteriuria | Positive urine culture with no signs or symptoms | No treatment unless patient is: ● Pregnant ● About to undergo a urologic procedure ● Post renal transplant ● Neutropenic |
| Acute cystitis | Signs and symptoms (e.g., dysuria, urgency, frequency, suprapubic pain) AND pyuria (>5-10 WBC/hpf) AND positive urine culture ≥ 100,000 colonies | Uncomplicated: female, no urologic abnormalities, no stones, no catheter. ● TMP/SMX 1 DS PO q12H x 3 days OR ● Cephalexin 500 mg PO q6H x 7 days OR ● Nitrofurantoin 100 mg PO q12H x 5 days (do NOT use in patients with CrCl < 40 ml/min) Complicated: male, stones, urologic abnormality, pregnancy. ● Same regimens as above, except duration is 7-14 days. |
| Acute pyelonephritis | Signs and symptoms (e.g., fever, flank pain) AND pyuria AND positive urine culture ≥ 100,000 colonies. Many patients will have other evidence of upper tract disease (i.e., leukocytosis, WBC casts, or abnormalities on imaging). | Patient not severely ill ● Ertapenem 1 g IV q24H OR ● Ceftriaxone 1 g IV q24H Duration 7-14 days Patient severely ill or hospitalized >48 hours ● Meropenem 1 g IV q8H OR ● Cefepime 1 g IV q8H OR ● PCN allergy: Aztreonam 1 g IV q8H Duration 7-14 days |
| Urosepsis | SIRS due to urinary tract infection | ● Meropenem 1 g IV q8H OR ● Cefepime 1 g IV q8H OR ● PCN allergy: Aztreonam 1 g IV q8H Duration 7-14 days |
Specimen collection: The uretheral area should be cleaned with an antiseptic cloth and the urine sample should be collected midstream or obtained by fresh catheterization. Specimens collected using a drainage bag or taken from a collection hat are not reliable and should not be sent.
Interpretation of the urinalysis (U/A) and urine culture
● Urinalysis and urine cultures must be interpreted together in context of symptoms.
● Urinalysis/microscopy:
   ○ Dipstick
■Nitrites indicate bacteria in the urine indicates the presence of a nitrate-reducing microorganism, such as Escherichia coli or any other member of the Enterobacteriaceae family.
■Leukocyte esterase indicates white blood cells in the urine
■Bacteria: presence of bacteria on urinalysis should be interpreted with caution and is not generally useful
   ○ Pyuria (more sensitive than leukocyte esterase): >5-10 WBC/hpf or >27 WBC/microliter
● Urine cultures:
   ○ If U/A is negative for pyuria, positive cultures are likely contamination.
   ○ Positive cultures with pyuria are defined as ≥ 100,000 (105) colonies. This cutoff is the most sensitive for a true UTI. Situations in which lower colony counts <105 are significant include: patients who are already on antibiotics at the time of culture, symptomatic young women, suprapubic aspiration, and men with pyuria.
TREATMENT NOTES
● Sterile pyuria (positive U/A, but negative culture results) typically requires no treatment, although if the patient has received antibiotics, the patient may still have a UTI. If sterile pyuria persists consider other causes (e.g., interstitial nephritis or cystitis, fastidious organisms such as TB).
● Follow-up urine cultures or U/A are only warranted for ongoing symptoms. They should NOT be acquired routinely to monitor response to therapy.
● See below for discussion of treatment options for VRE and renal concentrations of antibiotics.
Management of patients WITH a urinary catheter
| Category | Definition | Empiric Treatment |
| Asymptomatic bacteriuria | Positive urine culture with no signs or symptoms of infection. NOTE: obtaining routine cultures in asymptomatic patients is not recommended | Remove the catheter No treatment unless the patient is: ● Pregnant ● About to undergo a urologic procedure ● Post renal transplant ● Neutropenic Antibiotics do NOT decrease asymptomatic bacteriuria or prevent subsequent development of UTI |
| Catheter-associated UTI (CAUTI) | Signs and symptoms (fever with no other source is the most common; patients may also have suprapubic or flank pain) AND pyuria (>5-10 WBC/hpf) AND positive urine culture ≥ 100,000 colonies (see information below regarding significant colony counts) | ● Remove (PREFERRED) or replace catheter in all patients Patient stable with no evidence of upper tract disease: ● If catheter removed, consider observation alone OR ● Ertapenem 1 g IV q24H OR ● Ceftriaxone 1 g IV q24H OR ● Ciprofloxacin 500 mg PO BID or 400 mg IV q12H (avoid in pregnancy and in patients with prior exposure to quinolones) Duration: see treatment notes Patient severely ill, with evidence of upper tract disease, or hospitalized >48 H: ● Meropenem 1 g IV q8H OR ● Cefepime 1 g IV q8H OR ● PCN allergy: Aztreonam 1 g IV q8H Duration: 7-14 days |
Specimen collection: urine sample should be drawn in a sterile fashion from a fresh catheter specimen. It should be drawn from either the catheter itself or through the port designed specifically for this purpose, NOT from the urine collection bag. Specimen collection is critical since colonization of the Foley bag or actual catheter is common.
Symptoms: Catheterized patients often lack typical symptoms of dysuria, although fever, suprapubic pain, and flank pain may still be present.
Interpretation of the urinalysis and urine culture:
● Pyuria: defined as >5-10 WBC/hpf or >27 WBC/microliter. In the presence of a catheter, pyuria or positive cultures are not always a reliable indicator of infection. Lack of pyuria suggests no active infection.
● Positive urine culture: ≥100,000 colonies is the most specific for true CAUTI. Some experts state that ≥1,000 colonies represents significant bacteriuria; however, if this count is used, there should be a strong clinical suspicion of CAUTI based on symptoms and absence of infection at another site.
TREATMENT NOTES
● Remove catheter whenever possible.
● The duration of treatment has not been well-studied for CAUTI.
● Assess the degree of illness, comorbidities, and clinical response to determine duration of therapy. As a general guide:
   ○ If the catheter is removed and the patient is not severely ill and has good response to treatment: 5-7 days.
   ○ If the catheter remains present or the patient is severely ill (e.g. urosepsis) or has pyelonephritis: 7-14 days.
Treament of UTI due to Enterococci
● Almost all E. faecalis isolates are susceptible to Amoxicillin 500 mg PO TID OR Ampicillin 1 g IV q6H and should be treated with these agents. For patients with PCN allergy: Nitrofurantoin 100 mg PO BID (do NOT use in patients with CrCl < 40 mL/min).
● E. faecium (commonly vancomycin resistant)
   ○ Nitrofurantoin 100 mg PO BID if susceptible (do NOT use in patients with CrCl < 40 mL/min)
   ○ Doxycycline 100 mg PO BID if susceptible
   ○ Fosfomycin 3 g PO once (if female without catheter or catheter is removed; ask the micro lab for susceptibility)
   ○ Linezolid 600 mg PO BID OR fosfomycin 3 g PO every 2-3 days (max 21 days) if complicated UTI or catheter cannot be removed
Treatment of UTI due to extended spectrum beta-lactamase (ESBL)-producing organisms
● ESBLs are enzymes that confer resistance to ALL penicillins, cephalosporins, and aztreonam.
● Risk factors for infection or colonization: recent hospitalization, residence in a long-term care facility, prolonged use of broad spectrum antibiotics.
● Meropenem 1 g IV q8H should be used for all severe urinary infections if the organism is susceptible.
● Ertapenem 1 g IV q24H can be used for uncomplicated UTI.
● Ciprofloxacin or TMP/SMX can be used as alternatives to ertapenem for uncomplicated UTI if the organism is susceptible. Nitrofurantoin or fosfomycin may also be used for uncomplicated UTI if the organism is suceptible.
Renal excretion/concentration of selected antibiotics
● Good (>60%): aminoglycosides, amoxicillin, amoxicillin/clavulanate, fosfomycin, cefazolin, cefepime, cephalexin, ciprofloxacin, colistin, ertapenem, levofloxacin, trimethroprim/sulfamethoxazole, vancomycin, amphotericin B, fluconazole, flucytosine
● Variable (30-60%): cefpodoxime, linezolid (30%), doxycycline (29-55%), ceftriaxone, tetracycline (~60%)
● Poor (<30%): azithromycin, clindamycin, oxacillin, tigecycline, caspofungin, posaconazole, voriconazole
References:
Pyuria and urinary catheters: Arch Int Med 2000;160(5):673-77.
IDSA Guidelines for treatment of uncomplicated acute bacterial cystitis and pyelonephritis in women: Clin Infect Dis 1999;29:745.
European and Asian guidelines on management and prevention of CA-UTI: Int J Antimicrob Agents 2008; 31S:S68.
Approach to the Patient with Penicillin Allergy
Penicillin reactions - Incidence
● 80-90% of patients who report they are “allergic” to penicillin (PCN) actually have negative skin tests and are not at increased risk of an IgE-mediated allergic reaction.
● Penicillin reactions of some type occur in 0.7 to 10% of all patients who get the drug.
○ BUT: The incidence of anaphylactic reactions is 0.004% to 0.015%.
● Rates of cross-reactive IgE-mediated allergic reactions to cephalosporins in PCN-allergic patients appear to be uncommon (<5 but="" do="" occur.="" p="">
● Rates of PCN and carbapenem skin test cross reactivity are 47%, although clinical rates of hypersensitivity reactions in patients with reported PCN allergy who receive carbapenems are 9–11%.
● Cross reactions to monobactams (Aztreonam) do NOT appear to occur.
Penicillin skin testing
● When done correctly, PCN skin testing is highly predictive of serious, anaphylactic reactions.
● Patients with a negative skin test are NOT at risk for anaphylactic reactions.
● Rarely (1-3%), skin test negative patients may get mild hives and itching following penicillin administration but these RESOLVE with continued treatment.
● Skin test positive patients are at high-risk (50-75%) for serious IgE-mediated reactions with PCN exposure, and should avoid PCN agents or undergo a PCN desensitization procedure if no alternative agent exists.
● Skin tests cannot predict non-IgE mediated dermatologic reactions (delayed morbilliform rash or SJS/TEN), GI disturbances, or drug fevers.
Penicillin reactions — Types
● Immediate (Type 1/IgE-mediated) – Urticaria, angioedema, pruritus, flushing, anaphylaxis, hypotension, laryngeal edema, wheezing.
○ Typically occurs within minutes and nearly always within 4 within 1 hours of administration.
○ Potentially fatal if anaphylaxis, hypotension, respiratory distress occurs
○ Hypotension always occurs soon after administration
○ Can be predicted by skin tests
● Accelerated – Laryngeal edema, wheezing, angioedema, urticaria (NOT hypotension)
○ Occur within 1-72 hours of administration
○ Can be predicted by skin tests
● Late – Rash (maculopapular or morbilliform or contact dermatitis), destruction of RBC, WBC, platelets, serum sickness
○ Generally develops days to weeks into drug
○ Almost always occurs after 72 hours of administration
○ Morbilliform rashes sometimes resolve despite continued treatment
○ Maculopapular and morbilliform rashes generally DO NOT progress to Stevens-Johnson syndrome
○ Late reactions are NOT predicted by skin tests
● Stevens-Johnson Syndrome – exfoliative dermatitis with mucous membrane involvement
○ Generally occurs 1-3 weeks after drug administration.
○ May evolve from initial erythroderma, purpuric target lesions, or blisters
○ Almost always occur after 72 hours of administration
○ NOT predicted by a history of morbilliform rash OR by skin tests
Approach to the patient with reported penicillin allergy
● Brief, focused history can be VERY helpful.
● Questions to ask:
1. How long after beginning penicillin did the reaction occur?
2. Was there any wheezing, throat or mouth swelling, urticaria, or angioedema?
3. If a rash occurred, what was the nature of the rash? Where was it and what did it look like? Did the rash include any blistering or exfoliative features?
4. Was the patient on other medications at the time of the reaction?
5. Since then, has the patient ever received another penicillin or cephalosporin (ask about trade names like: Augmentin, Keflex, Ceftin, Vantin)?
6. If the patient received a beta-lactam subsequent to the initial reaction, what happened?
● The skin test nurse can be contacted (x5-4369) to perform PCN skin testing.
reporting penicillin allergy
● ANY patient who has a history consistent with an immediate reaction (any symptoms of urticaria, angioedema, laryngeal edema, wheezing, hypotension) SHOULD NOT receive beta-lactams without undergoing skin testing first EVEN IF they have received beta-lactams with no problems after the serious reaction.
○ Patients who report non-immediate (non-IgE) reactions and have received other penicillins without problems DO NOT have penicillin allergy and are not at increased risk for an allergic reaction compared to the general population.
○ Patients who report non-immediate reactions and have received cephalosporins can get cephalosporins but not necessarily PCNs.
○ Patients who report a history of a non-urticarial rash that is NOT consistent with Stevens-Johnson syndrome (target lesions with mucous membrane inflammation) after more then 72 hours of getting penicillin are not at increased risk for a serious hypersensitivity adverse reaction. They should, however, be watched closely for development of rashes.
○ Patients who report reactions consistent with serum sickness (rare) can receive either penicillins or cephalosporins with careful monitoring for recurrence.
○ Patients who report PCN-related GI symptoms (diarrhea, nausea) in the absence of other allergy symptoms are unlikely to have penicillin allergy and do not appear to be at increased risk for hypersensitivity adverse reactions. They should be closely observed for recurrent symptoms and be given supportive therapy if they occur.
References:
JAMA 2001;285:2498.
Use of carbapenems in patients with PCN allergy: J Antimicrob. Chemother 2004;54: 1155–7.
Ann Intern Med 2007;146:266–9.
Clostridium difficile infection (CDI)
TREATMENT
● STOP ALL ANTIMICROBIAL AGENTS WHENEVER POSSIBLE
● Oral therapy must be used whenever possible as the efficacy of IV metronidazole is poorly established for CDI and there is no efficacy of IV vancomycin for CDI.
Treatment depends on clinical severity
| Infection Severity | Clinical Manifestations |
| Asymptomatic carriage | C. difficile NAAT positive without diarrhea, ileus, or colitis |
| Mild or moderate | C. difficile NAAT positive with diarrhea but no manifestations of severe disease |
| Severe | C. difficile NAAT positive with diarrhea and one or more of the following attributable to CDI: ● WBC ≥ 15,000 ● Increase in serum Cr > 50% from baseline |
| Severe complicated | Criteria as above plus one or more of the following attributable to CDI: ● Hypotension ● Ileus ● Toxic megacolon or pancolitis on CT ● Perforation ● Need for colectomy ● ICU admission for severe disease |
| Infection Severity | Treatment |
| Asymptomatic carriage | Do NOT treat; treatment can promote relapsing disease |
| Mild or moderate | ● Metronidazole 500 mg PO/NGT q8h Unable to tolerate oral therapy: ● Metronidazole 500 mg IV q8h (suboptimal, see note above) |
| Severe | ● Vancomycin solution 125 mg PO/NGT q6h (preferred) OR ● Vancomycin capsules 125 mg PO q6h |
| Severe complicated | ● Consult Infectious Diseases and Surgery for evaluation for colectomy ● Vancomycin solution 500 mg NGT PLUS metronidazole 500 mg IV q8h Unable to tolerate oral therapy or complete ileus ● Vancomycin 500 mg in 100 ml NS q6h as retention enema via Foley catheter in rectum PLUS metronidazole 500 mg IV q8h |
● No response to oral metronidazole after 5 days of therapy
● Second episode of recurrent disease (first recurrence should be treated with metronidazole)
● Patients with significant side effects to metronidazole
● Patients who are pregnant
● Consider in patients > 80 years given reports of increased morbidity from CDI
Treatment Duration
● 10-14 days
Recurrent disease
● Resistance to metronidazole or vancomycin has not been conclusively documented
● Recurrent disease after a complete course of therapy occurs in ~25% of patients. Relapse is due to a failure to eradicate spores (60%) or acquisition of a new strain (40%). Recurrent disease documented by a positive NAAT test. Document recurrent disease with repeat stool testing.
● Some patients may develop irritable bowel syndrome after infectious colitis including CDI. This may be suggested by recurrent symptoms with negative stool testing.
● First recurrence should be treated the same as the initial episode.
● Second recurrence should be treated with vancomycin taper followed by pulse dosing.
● If serious or multiple recurrences, ID consult is advised.
| Vancomycin Taper Regimen |
| 125 mg 4 times daily x 10-14 days |
| 125 mg BID x 7 days |
| 125 mg daily x 7 days |
| 125 mg every 2-3 days for 2-8 weeks (pulse dosing) |
Diagnosis
● Do not send stool for C. difficile testing if patients do not have diarrhea, ileus, or colitis.
● The microbiology laboratory will reject non-diarrheal stools submitted for C. difficile testing.
● The present NAAT assay is >99% sensitive. Empiric treatment for patients with negative NAAT should be avoided.
● Repeat samples are unnecessary, as the negative predictive value of a single test is >99%.
● Stool for C. difficile testing should be collected prior to starting treatment for C. difficile.
● Do NOT send follow-up C. difficile toxins to document resolution of disease, as the test can remain positive for weeks following successful treatment.
● The microbiology laboratory will only accept 1 stool specimen per patient per 7 day period, and will only retest patients if 10 days have elapsed since a previous positive result.
Management
● Surgical intervention for total colectomy should be considered early if patient is clinically unstable secondary to CDI.
● Most patients with severe CDI should undergo abdominal CT to rule out toxic megacolon or pancolitis.
● Early therapy appears to be important, especially in elderly patients. It may be necessary to discontinue the offending agent and initiate therapy while the toxin assay is pending.
● Do not use antimotility agents (e.g., imodium)
● The offending agents should be discontinued. If antimicrobials are necessary, it is preferable to avoid clindamycin, cephalosporins, or fluoroquinolones.
● Prophylactic use of oral metronidazole or vancomycin in patients receiving antimicrobial therapy for treatment of underlying infection (other than CDI) is not recommended and may increase the patient’s risk for CDI.
● There are insufficient data to support the routine use of probiotics for CDI.
● Cholestyramine is of questionable efficacy and binds oral vancomycin. Its use is not advised.
Infection control
● All patients with CDI require contact isolation with spore precautions (hand wash, no alcohol gel).
● C. difficile spores extensively contaminate environmental surfaces and gowns/gloves are required for room entry even if the patient is not touched.
● Patients should remain in contact isolation for the duration of their hospitalization (see policy HS IC-003)
References:
Diagnosis of CDI: Clin Infect Dis 2008; 46:S12-8.
Treatment of CDI: Clin Infect Dis 2008; 46:S32-42.
Lack of utility of treating CDI carriers: Ann Intern Med 1992; 117:297-302.
Colectomy in CDI: Ann Surg 2007; 245:267-72.
The guidelines for the prevention of infective endocarditis (IE) issued by the American Heart Association underwent a major revision in 2007. Key changes include the following:
● Dental procedures have been found to be associated with a small number of cases of IE. Prophylaxis, even if 100% effective, would thus prevent only an extremely small number of cases.
● The emphasis has shifted from antibiotic prophylaxis to good oral health and increased access to dental care.
● Prophylactic antibiotics based on a patient’s lifetime risk for acquiring IE are no longer recommended. Instead, prophylaxis focuses on patients with the highest risk for adverse outcomes from endocarditis.
Candidates for Prophylaxis
Only those patients with conditions associated with the highest risk for adverse outcomes from IE should receive prophylaxis. These high-risk conditions include:
● Prosthetic cardiac valves
● Previous IE
● Congenital heart disease (CHD) only for the following specific conditions:
○ Unrepaired cyanotic CHD, including palliative shunts and conduits
○ Completely repaired congenital heart defect with prosthetic material or a prosthetic device placed either during surgery or by catheter intervention, during the first 6 months after the procedure
○ CHD repair with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device
● Development of cardiac valvulopathy after cardiac transplantation
Dental Procedures
Prophylaxis is directed against viridans-group streptococci.
● Procedures for which dental prophylaxis should be given to appropriate candidates include any procedures that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the oral mucosa.
● Procedures that do not require prophylaxis include routine anesthetic injections through noninfected tissues, dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, and placement of orthodontic brackets. Prophylaxis is also not necessary after the shedding of deciduous teeth or for bleeding from trauma to the lips or oral mucosa.
Prophylactic Regimens for Infective Endocarditis Before Dental Procedures
| Clinical Situation | Adult prophylaxis |
| Oral regimen | amoxicillin 2 g oral |
| Unable to take oral medication | ampicillin 2 g IM or IM OR cefazolin 1 g IM or IV OR ceftriaxone 1 g IM or IV |
| Allergy to penicillin or ampicillin (oral regimen) | cephalexin 2 g oral OR clindamycin 600 mg oral OR azithromycin 500 mg oral OR clarithromycin 500 mg oral |
| Allergy to penicillin or ampicillin (unable to take oral regimen) | cefazolin 1 g IM or IV OR ceftriaxone 1 g IM or IV OR clindamycin 600 mg IM or IV |
● Give single dose 30-60 minutes before procedure.
● If the antibiotic is inadvertently not administered before the procedure, it may be administered up to 2 hours after the procedure.
● Do not use cephalosporins in patients with a history of anaphylaxis, angioedema, or urticaria with penicillin.
● If a patient is already receiving long-term antibiotic therapy with an antibiotic that is also recommended for IE prophylaxis, an antibiotic from a different class should be used.
Respiratory Procedures
For candidates for prophylaxis as listed above.
● It may be reasonable to give one of the above prophylactic regimens recommended for dental procedures before an invasive procedure (e.g., tonsillectomy) involving the respiratory tract that necessitates incision or biopsy of the respiratory mucosa.
● Prophylaxis is not recommended for bronchoscopy unless the procedure involves incision of the respiratory tract mucosa.
Gastrointestinal or Genitourinary Procedures
For candidates for prophylaxis as listed above.
● Prophylaxis solely to prevent IE is no longer recommended.
● For patients scheduled for an elective urinary tract manipulation who also have an enterococcal urinary tract infection or colonization, it may be reasonable to administer antibiotic therapy to eradicate enteroccci from the urine before the procedure.
● If the urinary tract procedure is not elective, it may be reasonable to administer an antimicrobial regimen to the patient that contains an agent active against enterococci.
● Amoxillin or ampicillin is the preferred agent for enterococcal coverage; vancomycin may be administered to patients unable to tolerate ampicillin.
Procedures Involving Infected Skin or Soft Tissue
For candidates for prophylaxis as listed above.
● It is reasonable that the regimen administered for treatment of the infection contain an agent active against staphylococci and beta-hemolytic streptococci.
● An antistaphylococcal penicillin or cephalosporin is preferable; vancomyin or clindamycin may be administered to patients unable to tolerate a beta-lactam or who are known or suspected to have an infection cause by MRSA.
Reference
Wilson et al. Circulation. 2007 Apr 19;115.
