The Clinical Significance of Vancomycin Minimum Inhibitory Concentration in Staphylococcus aureus Infections: A Systematic Review and Meta-analysis

Abstract

High vancomycin MIC was associated with a higher mortality rate in MRSA BSI. Thus, institutions should consider conducting Etest MICs on all MRSA BSI isolates. Although these data highlight concerns about vancomycin, currently, there are no data to support better survival rates with alternative antibiotics. Data are sorely needed to determine whether other agents can remedy these outcomes observed with vancomycin for MRSA infections with elevated vancomycin MIC values.

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

“…However, with a recent systematic review and meta-analysis showing greater failure rates and mortality with MICs of 1.5 mg/L or 2 mg/L (i.e. within 1 doubling dilution of the current breakpoint), the discrimination between susceptible and less susceptible isolates has become difficult and hence the precision of automated systems has come under greater scrutiny [12].…”

“…Meta-analyses have consistently shown poorer outcomes with MICs approaching the breakpoint (>1 mg/L), including mainly episodes of bacteraemia but also pneumonia and skin and soft-tissue infections (SSTIs) [12][13][14]. The vancomycin MIC was significantly associated with mortality for MRSA infection irrespective of the source of infection or MIC methodology [odds ratio (OR) = 1.64, 95% confidence interval 1.14-2.37], although this was mostly attributable to bloodstream infections and Etest MICs of 2 mg/L [12]. It is acknowledged that the data used for these meta-analyses are retrospective, that potential confounding factors were not controlled and that the MIC was measured with different techniques.…”

Treatment of severe MRSA infections: current practice and further development

“…According to the 2009 Infectious Diseases Society of America (IDSA) vancomycin therapeutic guidelines [2], a loading dose of 25-30 mg/kg actual body weight should be used, followed by 15-20 mg/ kg q8-12 h. Vancomycin serum levels and vancomycin MRSA MIC by Etest must be measured routinely. Trough levels between 15 and 20 μg/mL are recommended [2], but the probability of target attainment is unlikely in high vancomycin MIC infections, and MIC values above 1 μg/ mL significantly predict treatment failure and mortality [3]. Although these outcomes may not reflect antibiotic failure per se but may rather be a marker of specific pathogen virulence characteristic, as a similar association between high vancomycin MIC and outcomes was reported in MSSA infections treated with flucloxacillin [4], it seems wise to aim at higher vancomycin levels in the case of MRSA MIC > 1 μg/mL.…”

Successful Treatment of Persistent MRSA Bacteremia using High-dose Daptomycin Combined with Rifampicin

“…Strains with a VCM-MIC of 2-4 μg/mL had previously been categorized as VCM-sensitive strains, but are now considered to have intermediate susceptibility (22). At present, a VCM-MIC of less than 2 μg/mL is judged to indicate sensitivity; however, even among such strains, higher MIC strains (more than 1 or 1.5 μg/mL) have been increasingly emerging (21,(23)(24)(25)(26). This phenomenon of "MIC creeping" has been widely reported (27), and the use of VCM for MRSA strains with such higher MIC values has been demonstrated to be related to treatment failure (24,28,29).…”