Vancomycin

Vancomycin is not appreciably absorbed from a normal gastrointestinal tract after oral administration. Given parenterally, it penetrates into bile and pleural, pericardial, synovial, and ascitic fluids. However, penetration into even inflamed cerebrospinal fluid is low and erratic.

Vancomycin is excreted unchanged by glomerular filtration.

Vancomycin is active against

• Most gram-positive cocci and bacilli, including almost all Staphylococcus aureus and coagulase-negative staphylococcal strains that are resistant to penicillins and cephalosporins

• Many strains of enterococci (mostly Enterococcus faecalis)

However, many strains of enterococci and some strains of S. aureus are resistant.

Vancomycin is often used for serious infection and endocarditis caused by the following (except for vancomycin-resistant strains):

• Methicillin-resistant S. aureus

• Methicillin-resistant coagulase-negative staphylococci

• Certain beta-lactam–resistant and multidrug-resistant Streptococcus pneumoniae

• Beta-hemolytic streptococci (when beta-lactams cannot be used because of drug allergy or resistance)

• Corynebacterium species including C. jeikeium, and C. striatum

• Viridans streptococci (when beta-lactams cannot be used because of drug allergy or resistance)

• Enterococci (when beta-lactams cannot be used because of drug allergy or resistance)

However, vancomycin is less effective than antistaphylococcal beta-lactams for methicillin-susceptible S. aureus infections. Vancomycin is used with other antibiotics when treating methicillin-resistant coagulase-negative staphylococcal prosthetic valve endocarditis or enterococcal endocarditis. Vancomycin has also been used as an alternative drug for pneumococcal meningitis caused by strains with reduced penicillin sensitivity; however, the erratic penetration of vancomycin into cerebrospinal fluid (especially during concomitant use of dexamethasone) and reports of clinical failures make it less than optimal when used alone to treat pneumococcal meningitis.

Oral vancomycin is used to treat Clostridioides (formerly, Clostridium) difficile–induced diarrhea (pseudomembranous colitis). Vancomycin is recommended over metronidazole for an initial episode of nonsevere C. difficile infection. It is preferred over metronidazole for patients who have severe C. difficile infection and is preferred for patients who do not respond to metronidazole. However, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 2021 clinical practice guidelines on the management of Clostridioides difficile infection in adults recommend that fidaxomicin (when available) be used over vancomycin for C. difficile infection.

Vancomycin is contraindicated in patients who have had an allergic reaction to it.

Animal reproduction studies with vancomycin have not shown risk to the fetus. Evidence in human studies is inadequate. Vancomycin should be given to pregnant women only if clearly needed. Oral vancomycin can be used to treat C. difficile–induced diarrhea in pregnant women.

Vancomycin enters breast milk, and so its use during breastfeeding is discouraged to prevent disruption of gastrointestinal microbiota; however, because oral absorption is poor from a normal gastrointestinal tract, systemic adverse effects in infants are unlikely.

The main concern with vancomycin is

• Hypersensitivity (allergic or due to direct mast-cell degranulation)

Vancomycin should be infused slowly in a dilute solution (2.5 to 5.0 mg/mL) over 60 minutes or more and at a rate no greater than 10 mg/minute to avoid vancomycin infusion reaction (a histamine-mediated reaction that can cause pruritus and flushing on the face, neck, and shoulders). Other hypersensitivity reactions (eg, rash, fever) may occur, especially when therapy lasts for > 2 weeks.

Other potential adverse effects include reversible neutropenia and thrombocytopenia. Nephrotoxicity is rare unless high doses are used or other nephrotoxins (eg, aminoglycosides) are given concomitantly. Some reports suggest that concomitant use of piperacillin/tazobactam may also increase risk of nephrotoxicity. Phlebitis occurs uncommonly during IV infusion.

Dose-related ototoxicity is unusual with current formulations; incidence is increased when vancomycin is given concurrently with other ototoxic drugs.

Doses used for meningitis must be higher than usual.

Dose reduction is required in renal insufficiency.

In patients with documented or suspected invasive methicillin-resistant S. aureus (MRSA) infection, vancomycin should be dosed to target an area under the concentration-time curve (AUC) of 400 to 600. Targeting troughs as a surrogate marker for achieving an AUC-to-minimum inhibitory concentration (AUC/MIC) ratio of ≥ 400 is no longer recommended. Dose optimization can be done by getting multiple post-distribution levels (1 to 2 hours after the end of the infusion and a trough) and calculating the AUC using first-order kinetic equations, using a software-based Bayesian approach using 1 or 2 levels, or by titrating a continuous infusion to a steady-state concentration of 20 to 25 mcg/mL (13.8 to 17.25 micromol/L). (See also the 2020 therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections guidelines revised by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.)

These dosing recommendations apply only to MRSA and should not be used to guide dosing for other gram-positive infections.

Vancomycin MICs for many pathogens have been increasing during the past decade. Sensitivity for S. aureus based on vancomycin MIC is as follows:

• ≤ 2 mcg/mL (≤ 1.4 micromol/L): Sensitive

• 4 to 8 mcg/mL (2.8 to 5.5 micromol/L): Intermediate

• > 8 mcg/mL (> 5.5 micromol/L): Resistant

However, infections due to S. aureus with a vancomycin MIC ≥ 2 mcg/mL (≥ 1.4 micromol/L) may respond suboptimally to standard dosing even when the daily AUC is 400 to 600, so the threshold for changing to an alternative therapy should be low for patients with poor clinical response and an MIC of ≥ 2.

The following are English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

1. Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): Focused update guidelines on the management of Clostridioides difficile infection in adults (2021)

2. American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists: Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections guidelines (2020)