Antibiotics

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
○ 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

● Salvage therapy for VRE infections other than pneumonia, on a case-by-case basis

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.