Vancomycin: A 50-something-year-old antibiotic we still don’t understand
ABSTRACTBecause a significant proportion of Staphylococcus aureus strains as well as most coagulase-negative staphylococci are resistant to penicillin and semisynthetic beta-lactam drugs, the need for vancomycin and related antibiotics has never been greater. Effective use of vancomycin requires knowledge of dosing parameters and selection of target trough levels appropriate to the specific infection and to the pathogen being treated. For clinicians, it is vital to remain up-to-date with evolving definitions for vancomycin susceptibility, with new interpretations of efficacy, and with information on toxicity.
KEY POINTS
- Giving vancomycin by continuous infusion appears to offer no advantage over giving it every 12 hours.
- Therapeutic blood levels can be reached more quickly if a loading dose is given, but whether this offers a clinical advantage is unclear.
- The trough vancomycin serum concentration should be greater than 10 mg/L to prevent the development of resistance, and trough levels of 15 to 20 mg/L are recommended if the minimum inhibitory concentration (MIC) is 1 mg/L or higher.
- Whether S aureus is becoming resistant to vancomycin is not clear.
- The variable most closely associated with clinical response to vancomycin is the area under the curve (AUC) divided by the MIC (the AUC-MIC ratio), which should be greater than 400.
Don’t use vancomycin when another drug would be better
Vancomycin continues to be the drug of choice in many circumstances, but in some instances its role is under scrutiny and another drug might be better.
Beta-lactams. In patients with infection due to methicillin-susceptible S aureus, failure rates are higher with vancomycin than with beta-lactam therapy, specifically nafcillin.35–37 Beta-lactam antibiotics are thus the drugs of choice for treating infection with beta-lactam-susceptible strains of S aureus.
Linezolid. In theory, linezolid’s ability to decrease production of the S aureus Panton-Valentine leukocidin (PVL) toxin may be an advantage over vancomycin for treating necrotizing pneumonias. For the treatment of MRSA pneumonia, however, controversy exists as to whether linezolid is superior to vancomycin. An analysis of two prospective, randomized, double-blind studies of patients with MRSA pneumonia suggested that initial therapy with linezolid was associated with better survival and clinical cure rates,38 but a subsequent meta-analysis did not substantiate this finding.39 An additional comparative study has been completed, and analysis of the results is in progress.
Daptomycin, approved for skin and soft-tissue infections and bacteremias, including those with right-sided endocarditis, is a lipopeptide antibiotic with a spectrum of action similar to that of vancomycin.40 Daptomycin is also active against many strains of vancomycin-resistant enterococci. As noted above, in the MRSA subgroup of the pivotal comparative study of treatment for S aureus bacteremia and endocarditis, the success rate for daptomycin-treated patients (44.4%) was better than that for patients treated with vancomycin plus gentamicin (32.6%), but the difference was not statistically significant.33,41
The creatine phosphokinase concentration should be monitored weekly in patients on daptomycin.42 Daptomycin is inactivated by lung surfactant and should not be used to treat pneumonia.
Other treatment options approved by the US Food and Drug Administration (FDA) for MRSA infections include tigecycline (Tygacil), quinupristin-dalfopristin (Synercid), telavancin (Vibativ), and ceftaroline (Teflaro).
Tigecycline is a glycylcycline with bacteriostatic activity against S aureus and wide distribution to the tissues.43
Quinupristin-dalfopristin, a streptogramin antibiotic, has activity against S aureus. Its use may be associated with severe myalgias, sometimes leading patients to stop taking it.
Telavancin, recently approved by the FDA, is a lipoglycopeptide antibiotic.44 It is currently approved to treat complicated skin and skin structure infections and was found to be not inferior to vancomycin. An important side effect of this agent is nephrotoxicity. A negative pregnancy test is required before using this agent in women of childbearing potential.
Ceftaroline, a fifth-generation cephalosporin active against MRSA, has been approved by the FDA for the treatment of skin and skin structure infections and community-acquired pneumonia.45
