Vancomycin
Vancomycin is a tricyclic glycopeptide antibiotic derived from the soil bacterium Amycolatopsis orientalis (formerly Streptomyces orientalis), primarily used to treat severe infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug-resistant strains.[1][2] Discovered in 1952 from soil samples collected in the jungles of Borneo, it was introduced clinically in the late 1950s as a last-resort option for infections resistant to earlier antibiotics like penicillin.[3] Vancomycin exerts its bactericidal effects by binding to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of peptidoglycan precursors in the bacterial cell wall, inhibiting transpeptidation and transglycosylation steps essential for cell wall synthesis, which leads to bacterial cell death.[4][5] This narrow-spectrum activity targets aerobic and anaerobic gram-positive organisms such as staphylococci, streptococci, enterococci, and clostridia, but it has no effect on gram-negative bacteria due to their outer membrane barrier.[1][6] Due to its poor oral bioavailability for systemic use, vancomycin is typically administered intravenously to achieve therapeutic plasma levels for serious conditions like endocarditis, bacteremia, pneumonia, bone and joint infections, and skin and soft tissue infections.[1] Orally, it is employed for non-systemic gastrointestinal infections, particularly Clostridium difficile-associated colitis, where it remains active in the gut lumen without significant absorption.[7][8] Alternative routes, such as intrathecal or topical, may be used for specific localized infections like meningitis or peritoneal dialysis-related peritonitis.[8] Despite its efficacy, vancomycin use is monitored closely due to risks of nephrotoxicity, ototoxicity, and the emergence of resistance mechanisms, such as vancomycin-resistant enterococci (VRE) and vancomycin-intermediate S. aureus (VISA).[9][10]Medical uses
Indications
Vancomycin is primarily indicated for the treatment of serious or severe infections caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE).[11] When administered intravenously, it is approved for conditions such as septicemia, infective endocarditis, infections of the bone and joints, lower respiratory tract infections, and skin and soft tissue infections due to these organisms.[11] Orally, vancomycin is specifically indicated for the treatment of Clostridioides difficile-associated diarrhea (CDAD) in both adults and pediatric patients. In clinical practice, vancomycin serves as a cornerstone therapy for various Gram-positive infections, including complicated skin and soft tissue infections, bacteremia, endocarditis, osteomyelitis, septic arthritis, and hospital-acquired or ventilator-associated pneumonia suspected to involve MRSA.[12] It is particularly valuable for patients allergic to beta-lactams or those with infections unresponsive to other agents.[1] For surgical prophylaxis, guidelines recommend vancomycin in high-risk procedures such as cardiac, orthopedic, vascular, and neurosurgical interventions when there is known MRSA colonization, beta-lactam allergy, or high institutional MRSA prevalence, typically as an alternative to cefazolin. The Infectious Diseases Society of America (IDSA) guidelines endorse vancomycin as a first-line agent for serious MRSA infections, including bacteremia and endocarditis (with or without prosthetic valves), complicated skin and soft tissue infections, pneumonia, and bone and joint infections.[12] For optimal efficacy, vancomycin therapy often targets an area under the curve to minimum inhibitory concentration (AUC/MIC) ratio of ≥400.[13] For CDI, the 2021 IDSA/SHEA guidelines suggest fidaxomicin as the preferred initial therapy for nonsevere and severe episodes, with oral vancomycin (125 mg four times daily) as an acceptable alternative; for fulminant cases, oral (or nasogastric) vancomycin (500 mg four times daily) is recommended as first-line, with both fidaxomicin and vancomycin outperforming metronidazole in clinical outcomes.[14] Off-label uses of vancomycin include treatment of susceptible enterococcal infections, such as endocarditis caused by vancomycin-susceptible Enterococcus faecalis or Enterococcus faecium, typically in combination with gentamicin or as an alternative for beta-lactam-intolerant patients.[15] It may also be employed for other resistant Gram-positive infections where susceptibility is confirmed, though emerging resistance patterns necessitate careful microbiological guidance.[1]Spectrum of activity
Vancomycin exhibits potent activity against a broad range of Gram-positive bacteria, including staphylococci (such as methicillin-resistant Staphylococcus aureus [MRSA]), streptococci, enterococci, and Gram-positive anaerobes like Clostridioides species (e.g., C. difficile) and other Clostridium species.[16] This selectivity arises because vancomycin inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of peptidoglycan precursors, a process accessible in Gram-positive organisms lacking an outer membrane.[4] In vitro susceptibility testing demonstrates low minimum inhibitory concentrations (MICs) for most susceptible Gram-positive strains. For example, the MIC for S. aureus is typically ≤2 μg/mL, with MIC90 values of 2 μg/mL reported for MRSA isolates.[16][17] Against streptococci, including Streptococcus pneumoniae, MICs range from 0.25 to 2 μg/mL, while for vancomycin-susceptible enterococci, they generally fall between 1 and 4 μg/mL.[18] Vancomycin also shows strong anaerobic activity, particularly against Clostridioides difficile, with MICs for susceptible strains typically 0.5–2 μg/mL, supporting its efficacy in this context.[19] Vancomycin is inherently ineffective against most Gram-negative bacteria due to its inability to penetrate the outer membrane, resulting in MICs exceeding 64 μg/mL for pathogens like Escherichia coli.[20][21] The accuracy of in vitro susceptibility testing for vancomycin can be influenced by factors such as inoculum size and testing media. Higher inoculum levels may elevate MICs, particularly for staphylococci and enterococci, due to the inoculum effect, while cation concentrations in media (e.g., calcium and magnesium) can alter results.[22][23]| Bacterium | Typical MIC Range for Susceptible Strains (μg/mL) |
|---|---|
| Staphylococcus aureus (including MRSA) | 0.5–2 |
| Streptococci (e.g., S. pneumoniae) | 0.25–2 |
| Vancomycin-susceptible enterococci | 1–4 |
| Clostridioides difficile | 0.5–2 |