Is vancomycin redundant for serious staphylococcal infection?

Abstract

Vancomycin's clinical utility is under serious threat. Intensive use has created selective pressure and many databases record modal minimum inhibitory concentrations (MICs) of ≥1 mg/L. Although the current breakpoint is 2 mg/L this is reasonably well established as having no clinical relevance. Unfortunately, setting a clinical breakpoint of 0.5 or 1 mg/L, which is argued persuasively by the available clinical data, would lead to a loss of reproducibility and frequent misclassification of susceptibility in the laboratory. Moreover, MIC testing is method-dependent and this adds further confusion when trying to ascertain the place of an antibiotic with such a narrow therapeutic window. The optimal pharmacokinetic/pharmacodynamic target of a total area under the curve (AUC)/MIC ratio of 400, although based on only a small number of publications, is backed up by the available clinical studies, albeit that they are non-randomised cohorts, often retrospective. Unfortunately, the toxicity of vancomycin would seem to prevent us from prolonging its useful life by increasing doses. Even if the AUC/MIC ratio 400 were reached, it is not clear that such doses would be more efficacious, as a raised MIC also heralds other changes in the organism, such as altered accessory gene regulation and tolerance, which may further diminish the drug's performance. Unless vancomycin use can be seriously reduced, continued selective pressure is quite likely to lead to further elevations in MICs and increased numbers of strains with intermediate or reduced susceptibility. The same conclusions almost certainly apply to teicoplanin.