What is vancomycin?

What is Vancomycin?

Vancomycin is a tricyclic glycopeptide antibiotic that is bactericidal against gram-positive organisms, serving as the drug of choice for serious methicillin-resistant staphylococcal infections and for patients with serious gram-positive infections who cannot receive beta-lactam antibiotics. 1

Chemical Structure and Mechanism

• Vancomycin is derived from Amycolatopasis orientalis (formerly Nocardia orientalis) and has a molecular weight of 1,485.74 1
• It interferes with peptidoglycan biosynthesis in multiplying organisms, making it bactericidal through multiple modes of action 2, 3
• The drug is oxygen sensitive and must be administered intravenously in diluted solution after reconstitution 1

Antibacterial Spectrum

Vancomycin has a narrow spectrum of activity limited to gram-positive organisms only:

• Active against staphylococci (including methicillin-resistant S. aureus and S. epidermidis) 1, 4
• Covers streptococci (including viridans streptococci and S. bovis) 1, 4
• Effective against enterococci (though requires combination with an aminoglycoside for endocarditis) 1, 4
• Active against diphtheroids and Corynebacterium jeikeium 5, 1
• Effective against Clostridium difficile when given orally for antibiotic-associated colitis 1, 3
• Has NO activity against gram-negative bacteria, including Klebsiella species, due to the outer membrane barrier 6

FDA-Approved Indications

The FDA label specifies vancomycin is indicated for:

• Serious or severe infections caused by methicillin-resistant (β-lactam-resistant) staphylococci 1
• Penicillin-allergic patients with gram-positive infections 1
• Staphylococcal endocarditis (documented effectiveness) 1
• Septicemia, bone infections, lower respiratory tract infections, and skin/skin structure infections due to staphylococci 1
• Endocarditis caused by S. viridans or S. bovis (alone or with aminoglycoside) 1
• Enterococcal endocarditis (only in combination with an aminoglycoside) 1
• Diphtheroid endocarditis 1
• Early-onset prosthetic valve endocarditis caused by S. epidermidis (in combination with rifampin and/or aminoglycoside) 1
• Oral administration for antibiotic-associated pseudomembranous colitis caused by C. difficile and staphylococcal enterocolitis 1

Clinical Situations Where Vancomycin Use is Appropriate

According to CDC/HICPAC guidelines, vancomycin use is appropriate in:

• Treatment of serious infections caused by beta-lactam-resistant gram-positive microorganisms 5
• Treatment of gram-positive infections in patients with serious beta-lactam allergies 5
• Antibiotic-associated colitis that fails metronidazole or is severe and life-threatening 5
• Endocarditis prophylaxis as recommended by the American Heart Association for certain high-risk procedures 5
• Surgical prophylaxis for prosthetic implant procedures at institutions with high MRSA rates (single dose, maximum two doses) 5

For febrile neutropenic patients, vancomycin should be included in initial empirical therapy only when: 5

• Clinically suspected serious catheter-related infections (bacteremia, cellulitis) 5
• Known colonization with penicillin/cephalosporin-resistant pneumococci or MRSA 5
• Positive blood cultures for gram-positive bacteria before final identification 5
• Hypotension or cardiovascular impairment 5
• Initial evidence of gram-positive infection at catheter exit sites when institutional MRSA prevalence is substantial 5

Situations Where Vancomycin Should Be Discouraged

The CDC/HICPAC explicitly recommends against vancomycin use in:

• Routine surgical prophylaxis (except for life-threatening beta-lactam allergy) 5
• Empiric therapy for febrile neutropenia without evidence of gram-positive infection or high institutional MRSA rates 5
• Single positive blood culture for coagulase-negative staphylococcus when other cultures are negative (likely contamination) 5, 7
• Continued empiric use when cultures are negative for beta-lactam-resistant gram-positive organisms 5

Pharmacokinetics and Administration

• Vancomycin follows a two- or three-compartment pharmacokinetic model with biphasic disposition 2, 3
• Almost completely eliminated through the kidneys by glomerular filtration 2, 3
• Usual adult dose is 500 mg every 6 hours or 1 g every 12 hours in patients with normal renal function 4, 2
• Must be administered slowly over 30-60 minutes in adequate volume (100-250 mL) to prevent "red neck syndrome" 2, 3
• Achieves approximately 15% of serum concentrations in inflamed meninges, pleural fluid, pericardial fluid, ascitic fluid, synovial fluid, and bile 2

Therapeutic Monitoring

The most recent consensus recommendations establish:

• Trough serum concentration monitoring is the most accurate and practical method 8
• Target trough concentrations of 15-20 mg/L for serious infections to achieve AUC:MIC ratio ≥400 8
• Serum levels should be monitored in patients with impaired renal function 5, 7
• Peak serum levels should remain ≤30 mcg/mL to minimize neurotoxicity risk 4

Toxicity Profile

• "Red neck syndrome" (erythema at neck/upper back with possible hypotension) is the most common side effect, caused by rapid infusion 3
• Nephrotoxicity and ototoxicity are rare with conventional dosing but increase with doses ≥4 g/day 8, 3
• Increased nephrotoxicity risk when combined with aminoglycosides 5
• The toxic potential is less significant than historically thought 3

Critical Pitfalls to Avoid

• Never use vancomycin for gram-negative infections - it has zero activity against organisms like Klebsiella, Pseudomonas, or E. coli 6
• Do not use vancomycin when beta-lactam-susceptible S. aureus is identified - beta-lactams (oxacillin, nafcillin) are superior with faster bactericidal activity and lower failure rates 5
• Avoid continuing vancomycin beyond 24-48 hours in neutropenic patients if no gram-positive infection is identified 5
• Do not treat single positive coagulase-negative staphylococcus blood cultures without confirmation - this represents contamination and drives unnecessary resistance 5, 7
• Consider alternative therapies when S. aureus MIC to vancomycin is ≥2 mg/L - the target AUC:MIC ratio of ≥400 becomes unachievable 8

Resistance Concerns

• Vancomycin use is consistently reported as a risk factor for vancomycin-resistant enterococcus (VRE) colonization and infection 5
• May increase the possibility of vancomycin-resistant S. aureus (VRSA) and vancomycin-resistant S. epidermidis (VRSE) emergence 5
• Bacterial resistance rarely develops due to multiple modes of action 3
• Prudent use strategies are essential even at institutions where VRE has never been detected 5