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Vancomycin

by Hans P. Schlecht, MD, MSc, Christopher Bruno, MD

Vancomycin is a time-dependent bactericidal antibiotic that inhibits cell wall synthesis.

Pharmacology

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

Vancomycin is excreted unchanged by glomerular filtration.

Indications

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 (via a bacteriostatic mechanism)

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

Vancomycin is a drug of choice for serious infection and endocarditis caused by the following (except for vancomycin-resistant strains):

  • Methicillin-resistant S. aureus

  • Methicillin-resistant coagulase-negative staphylococci

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

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

  • Corynebacterium group JK

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

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

However, vancomycin is less effective than antistaphylococcal β-lactams for S. aureus endocarditis. 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 CSF (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 Clostridium difficile–induced diarrhea (pseudomembranous colitis—see Clostridium difficile –Induced Diarrhea). It is preferred over metronidazole for patients who have severe C. difficile infection and is preferred for patients who do not respond to metronidazole.

Contraindications

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

Use During Pregnancy and Breastfeeding

Vancomycin has not had adverse effects in animals, and evidence in human studies is inadequate. Oral vancomycin tablets are in pregnancy category B (animal studies show no risk and human evidence is incomplete, or animal studies show risk but human studies do not). Oral-solution vancomycin and IV vancomycin are in category C (animal studies show some risk, evidence in human and animal studies is inadequate, but clinical benefit sometimes exceeds risk).

Vancomycin enters breast milk, and so its use during breastfeeding is discouraged; however, because oral absorption is poor from a normal GI tract, adverse effects in infants are usually considered unlikely.

Adverse Effects

The main concern is

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

Vancomycin should be infused over ≥ 60 min to avoid red-person syndrome (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 wk.

Other adverse effects include reversible neutropenia and thrombocytopenia. Nephrotoxicity is rare unless high doses are used or an aminoglycoside is given concomitantly. 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.

Dosing Considerations

Doses used for meningitis must be higher than usual.

Dose reduction is required in renal insufficiency.

In critically ill patients, serum trough levels should be measured after the 2nd or 3rd dose and kept between 15 and 20 μg/mL.

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

  • ≤ 2 μg/mL: Sensitive

  • 4 to 8 μg/mL: Intermediate

  • > 8 μg/mL: Resistant

However, infections due to S. aureus with a vancomycin MIC of 2 to 8 μg/mL may respond suboptimally to standard dosing and require higher doses with trough levels between 15 to 20 μg/mL, but this approach may be complicated by increased rates of nephrotoxicity.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • VANCOCIN
  • FLAGYL
  • OZURDEX

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