Vancomycin

1. Introduction

Vancomycin is a glycopeptide antibiotic primarily active against Gram-positive organisms, especially MRSA and other resistant pathogens.

2. Mechanism of Action

Vancomycin:

• Binds to D-Ala–D-Ala terminus of peptidoglycan precursors
• Inhibits transglycosylation and transpeptidation
• Prevents bacterial cell wall synthesis
• Causes cell lysis (slow bactericidal effect)

Unlike β-lactams, vancomycin does not bind PBPs.
Resistance occurs when bacteria modify D-Ala–D-Ala → D-Ala–D-Lac.

3. Spectrum of Activity

Active Against:

• MRSA
• MSSA (not preferred if β-lactam sensitive)
• Coagulase-negative staphylococci
• Streptococci
• Enterococci (non-VRE)
• Penicillin-resistant Streptococcus pneumoniae
• Clostridioides difficile (oral only)

Not Active Against:

• Gram-negative bacteria
• Atypicals
• Mycobacteria

4. ICU Relevance:

• Adjust dose in renal failure
• Removed by high-flux dialysis
• Accumulates in AKI

5. Pharmacodynamics

Earlier: Trough-based monitoring
Now (Latest Guidelines): AUC/MIC-based dosing

Target:

AUC/MIC ≥ 400 (for MRSA with MIC ≤1)

• Trough-only monitoring is outdated.
• Target trough 15–20 mg/L may cause nephrotoxicity.

2020 IDSA/ASHP guidelines recommend AUC-based monitoring

6. Clinical Indications 

1. MRSA Sepsis

2. Infective Endocarditis

3. VAP (suspected MRSA)

4. Skin & Soft Tissue Infection

5. Bone & Joint Infection

6. C. difficile colitis (oral)

7.  Resistance Mechanisms

1. VISA (Vancomycin-Intermediate S. aureus)

• Thickened cell wall

2. VRSA (Vancomycin-Resistant S. aureus)

• Acquired VanA gene

3. VRE (Vancomycin-Resistant Enterococcus)

Associated with:

• Enterococcus faecium

8. Adverse Effects 

1. Nephrotoxicity

• Most important toxicity
• Risk increases with:
• High trough
• Piperacillin-tazobactam combination
• Prolonged use

2. Red Man Syndrome

• Histamine-mediated
• Rapid infusion
• Flushing, hypotension
• Prevent by slow infusion (>1 hr per gram)

3. Ototoxicity (rare)

4. Neutropenia (rare)

• MRSA Pneumonia → Linezolid preferred
• MRSA Bacteremia → Vancomycin or Daptomycin
• VRE Sepsis → Linezolid or Daptomycin
• Renal failure → Teicoplanin or Linezolid preferred
• Right-sided Endocarditis → Daptomycin excellent
• Need Oral Step-down → Linezolid only option
• Long ICU stay → Monitor Linezolid platelets