Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1 mg/L but ≤2 mg/L) and 'low-VMIC' (VMIC ≤ 1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR) = 1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR = 1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR = 1.19 (1.02-1.40), 2956 patients; treatment failure, RR = 1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC > 1 mg/L appears to be associated with higher mortality than VMIC ≤ 1 mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.