Vancomycin

Vancomycin is an antibiotic that is reserved, in intravenous form, for the treatment of multidrug-resistant infections, especially from Staphylococcus aureus, for the prophylactic or emergent treatment of patients with severe allergies to otherwise more appropriate antibiotics. In oral form, which is not absorbed systemically, it is indicated for Clostridium difficile intestinal infections, although metronidazole is now the first choice in these patients.

Until recently, it was the drug of last resort for multidrug resistant Staphylococci and Enterococci. While there are not widespread legal requirements for reporting vancomycin-resistant strains, organizations such as the Infectious Disease Society of America routinely take and disseminate reports.

Pharmacology

Vancomycin binds to the terminal D-Alanine-D-Alanine in the pentapeptide of the peptidoglycan precursor of susceptible bacteria, thus inhibiting transglycosilation (one of the key reactions in bacterial cell wall synthesis) by penicillin-binding proteins (PBP) and eventually leading to cell death.

The half life in normal individuals is 4-6 hours.

Vancomycin may be an example where pharmagological bioequivalence does not predict therapeutic bioequivalence.

Treatment

Staphylococcus aureus

Clinical practice guidelines endorsed by multiple expert organizations, summarized in Medscape Clinical News, address the use of vancomycin against Staphylococcus aureus:

• Dosing
  • Dosing must be individualized. Even in obese patients, the initial dose should be calculated on body weight. Subsequent dosage should be based on measured serum concentrations of vancomycin.(level of evidence, 2; grade of recommendation, A).
  • Compared with intermittent dosing, continuous infusion is not likely to significantly improve patient outcome (level of evidence, 2; grade of recommendation, A).
  • Because of conflicting evidence regarding comparative vancomycin toxicity for continuous vs intermittent administration, no recommendation can be made. The guidelines do not recommend monitoring serum vancomycin concentrations to prevent ototoxicity, because monotherapy seldom results in ototoxicity and there is no apparent correlation with serum vancomycin concentrations. However, monitoring may be more important during coadministration of aminoglycosides or other ototoxic agents (level of evidence, 3; grade of recommendation, B).
  • "To avoid the development of resistance, trough serum vancomycin concentrations should always be maintained at greater than 10 mg/L, based on evidence suggesting that exposure of S aureus to trough serum concentrations of less than 10 mg/L can produce strains with vancomycin–intermediately susceptible S aureus–like characteristics (level of evidence, 3; grade of recommendation, B).
• Monitoring
  • "The most accurate and practical way to monitor vancomycin effectiveness is by using trough serum vancomycin concentrations, which should be measured just before the fourth dose, at steady-state conditions (level of evidence, 2; grade of recommendation, B).
  • " Trough serum vancomycin concentrations of 15 to 20 mg/L are recommended because of the potential of these concentrations to improve penetration, to increase the likelihood of optimal target serum concentrations, and to improve clinical outcomes of complicated infections caused by S aureus, such as bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia. If the MIC is less than 1 mg/L, trough serum vancomycin concentrations of 15 to 20 mg/L should achieve an area under the curve/MIC of 1400 for most patients (level of evidence, 3; grade of recommendation, B). For seriously ill patients, a loading dose of 25 to 30 mg/kg (based on actual body weight) can be considered to rapidly reach this target concentration (level of evidence, 3; grade of recommendation, B).
  • "Because evidence is limited to support the safety of sustained trough serum vancomycin concentrations of 15 to 20 mg/L, once-weekly measurements of trough concentrations are recommended for hemodynamically stable patients in whom this target range is desired. To prevent toxicity in hemodynamically unstable patients, frequent or even daily monitoring of trough concentrations is recommended, although clinical judgment should guide the exact frequency of monitoring (level of evidence, 3; grade of recommendation, B).
  • " For patients with normal renal function, defined as creatinine clearance 70 to 100 mL/minute, a targeted area under the curve/MIC of more than 400 is not achievable with conventional dosing methods if the vancomycin MIC is 2 mg/L or higher, and alternative treatments should therefore be considered. To achieve the recommended trough serum concentrations when the MIC is less than 1 mg/L, most patients with normal renal function should receive vancomycin dosages of 15 to 20 mg/kg (based on actual body weight) given every 8 to 12 hours. The guidelines authors note that because currently available nomograms were not developed to achieve these targeted end points, individual pharmacokinetic adjustments and confirmation that target serum concentrations have been reached are recommended. The infusion period should be increased to 1.5 to 2 hours when individual doses greater than 1 g (eg, 1.5 and 2 g) are used (level of evidence, 3; grade of recommendation, B)
• Clinical toxicity
  • "Evidence to date for a direct causal relationship between toxicity and specific serum vancomycin concentrations is limited, and data are inconclusive because of confounding nephrotoxic agents, inconsistent and highly variable definitions of toxicity, and difficulty in assessing the time sequence of events regarding changes in renal function secondary to vancomycin exposure. In the absence of an alternative explanation, a patient should be considered to have vancomycin-induced nephrotoxicity if there are multiple (at least 2 or 3 consecutive) high serum creatinine concentrations (increase of 0.5 mg/dL or 150% increase from baseline, whichever is greater) after several days of vancomycin therapy (level of evidence, 2; grade of recommendation, B).
  • "Evidence to date does not suggest that monitoring of peak serum vancomycin concentrations will reduce the incidence of nephrotoxicity (level of evidence, 1; grade of recommendation, A). In patients receiving aggressive dose targeting to achieve sustained trough serum concentrations of 15 to 20 mg/L, or those at risk for toxicity (eg, because of concurrent treatment with nephrotoxins), monitoring of trough serum vancomycin concentrations to decrease nephrotoxicity is most appropriate (level of evidence, 3; grade of recommendation, B).
  • "In addition, patients with unstable renal function and those being treated for more than 3 to 5 days should also undergo monitoring (level of evidence, 2; grade of recommendation, B). All patients treated with vancomycin for 5 days or more should have at least 1 steady-state trough serum concentration measured just before the fourth dose. Frequent monitoring with more than 1 measurement of trough concentration before the fourth dose is not recommended for treatment lasting less than 5 days or for lower-intensity dosing targeted to achieve trough serum vancomycin concentrations of less than 15 mg/L (level of evidence, 2; grade of recommendation, B).

Adverse effects

Thrombocytopenia

Vancomycin may cause immune thrombocytopenia.

Acute kidney injury

Vancomycin is associated with acute kidney injury if trough levels are elevated. Above 15 microg/mL has been proposed as a threshold. To avoid this, the blood levels of vancomycin should be monitored.

Recommended trough levels are 15–20 mg/L.

External links

The most up-to-date information about vancomycin for injection and other drugs can be found at the following sites.

• vancomycin for injection - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
• vancomycin for injection - Drug information for consumers from MedlinePlus (U.S. National Library of Medicine).
• vancomycin for injection - Detailed information from DrugBank.