Predicting high vancomycin minimum inhibitory concentration isolate infection among patients with community-onset methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates with an elevated vancomycin MIC ≥2 mg/L have been increasingly identified in many countries. We aimed to develop a clinical score to predict vancomycin MIC ≥2 mg/L in patients with community-onset MRSA bacteraemia. This retrospective cohort study enrolled 394 patients with MRSA bacteraemia. Vancomycin MICs of all MRSA isolates were determined by agar dilution method. Clinical characteristics between patients with high (≥2 mg/L) and low (≤1 mg/L) vancomycin MIC MRSA bacteraemia were compared. Independent predictors of high vancomycin MIC isolate infection were identified and used to create a score-based predictive model. Among the 394 study patients, 56 (14.2%) had MRSA isolates with a vancomycin MIC ≥2 mg/L. The final regression model included 6 independent predictors: chronic liver disease (adjusted odds ratio [aOR], 2.99; 95% confidence interval [CI], 1.39-6.42), prior recovery of MRSA from respiratory tract specimen (aOR, 2.54; 95% CI, 1.15-5.61), end-stage renal disease (aOR, 2.53; 95% CI, 1.33-4.78), severe sepsis or septic shock on presentation (aOR, 2.39; 95% CI, 1.28-4.44), prior vancomycin exposure (aOR, 2.21; 95% CI, 1.13-4.30), and recent hospitalization within 3 months (aOR, 2.11; 95% CI; 1.01-4.40). All independent predictors had a value of one point. Youden's index statistics indicated a score of ≥3 as best cutoff value that had a sensitivity of 69.6% and specificity of 78.4%. Simple decision rule helps clinicians stratify the risk of high vancomycin MIC MRSA infection when deciding empirical therapy for patients with community-onset infections.

Chen SY ，Hsueh PR ，Chiang WC ，Huang EP ，Lin CF ，Chang CH ，Chen SC ，Chen WJ ，Chang SC ，Lai MS ，Chie WC ... -  《-》

High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia.

Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 μg/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC≥1 μg/mL and 79.8% for patients infected with isolates having a MIC<1 μg/mL (log-rank test, P=0.026). Vancomycin MIC≥1 μg/mL [hazard ratio (HR)=7.0, 95% confidence interval (CI) 2.2-22.1; P=0.001], nosocomial acquisition of bacteraemia (HR=5.4, 95% CI 1.4-20.1; P=0.013), rapidly fatal underlying diseases (HR=20.5, 95% CI 3.9-106.4; P<0.001), presentation with septic shock (HR=8.4, 95% CI 3.0-23.3; P<0.001), presence of complicated infections (HR=5.6, 95% CI 2.0-15.8; P=0.001) and persistent MRSA bacteraemia for ≥3 days (HR=4.2, 95% CI 1.4-12.7; P=0.012) were independent predictors of 30-day mortality in patients with MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score ≥2), the delay in initiation of vancomycin therapy was significantly different between non-survivors and survivors (2.4 days vs. 1.1 days; P=0.012). Vancomycin MIC≥1 μg/mL had a significant impact on mortality of patients with MRSA bacteraemia. These findings support early consideration of alternative anti-MRSA agents in patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially those with high Pitt scores.

Wi YM ，Kim JM ，Joo EJ ，Ha YE ，Kang CI ，Ko KS ，Chung DR ，Song JH ，Peck KR ... -  《-》

Methicillin-resistant Staphylococcus aureus (MRSA) staphylococcal cassette chromosome mec genotype effects outcomes of patients with healthcare-associated MRSA bacteremia independently of vancomycin minimum inhibitory concentration.

Chen SY ，Liao CH ，Wang JL ，Chiang WC ，Lai MS ，Chie WC ，Chen WJ ，Chang SC ，Hsueh PR ... -  《-》

Area under the concentration-time curve to minimum inhibitory concentration ratio as a predictor of vancomycin treatment outcome in methicillin-resistant Staphylococcus aureus bacteraemia.

There have been few clinical studies on the association between the 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. Patients with MRSA bacteraemia between July 2009 and January 2012 were analysed retrospectively. All adult patients treated with vancomycin for ≥72 h without dialysis were included. The MIC was determined by Etest and broth microdilution (BMD). Initial steady-state AUC24 was estimated using a Bayesian model, and the AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by classification and regression tree (CART) analysis. In total, 76 patients were enrolled; vancomycin treatment failure occurred in 20 patients (26.3%). Catheter-related infection was the most frequent (35.5%), followed by surgical site infection (26.3%), whilst 25 (32.9%) had complicated infections. In univariate analysis, decreased MRSA vancomycin susceptibility (MIC≥1.5 mg/L) and vancomycin trough levels (15-20 mg/L) were not associated with treatment outcomes. In the CART analysis, low initial vancomycin AUC24/MIC (<430 by Etest; <398.5 by BMD) was associated with a higher treatment failure rate (50.0% vs. 25.0%, P=0.039 by Etest; 45.0% vs. 23.2%; P=0.065 by BMD). In multivariate analysis, low initial vancomycin AUC24/MIC was a significant risk factor for treatment failure [adjusted odds ratio (aOR)=4.39, 95% confidence interval (CI), 1.26-15.35 by Etest; aOR=3.73, 95% CI 1.10-12.61 by BMD]. In MRSA bacteraemia, a low initial vancomycin AUC24/MIC is an independent risk factor for vancomycin treatment failure.

Jung Y ，Song KH ，Cho Je ，Kim HS ，Kim NH ，Kim TS ，Choe PG ，Chung JY ，Park WB ，Bang JH ，Kim ES ，Park KU ，Park SW ，Kim HB ，Kim NJ ，Oh MD ... -  《-》

High vancomycin minimum inhibitory concentrations with heteroresistant vancomycin-intermediate Staphylococcus aureus in meticillin-resistant S. aureus bacteraemia patients.

Patients with high vancomycin minimum inhibitory concentrations (MICs) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) infection are associated with treatment failure and poor outcomes. The main purpose of this study was to investigate the effect of hVISA on patient outcome, considering both the high vancomycin MIC and the existence of heteroresistant phenotypes. From January 2005 to December 2009, consecutive meticillin-resistant S. aureus (MRSA) isolates from 284 cases of MRSA bacteraemia receiving glycopeptide therapy were collected for further MIC and hVISA testing. The demographic distribution, clinical features and outcomes in bacteraemia patients with different vancomycin MICs and hVISA status in MRSA isolates were subsequently compared. Subjects were divided into three groups: low vancomycin MIC (<1.5mg/L) with vancomycin-sensitive S. aureus (VSSA) (n=50); high vancomycin MIC (≥1.5mg/L) with VSSA (n=218); and high vancomycin MIC with hVISA (n=16). Cox regression analysis demonstrated that the high MIC with VSSA group exhibited significantly higher 30-day mortality than the low MIC with VSSA group [odds ratio (OR)=2.349, 95% confidence interval (CI) 1.078-5.118]. The high MIC with hVISA phenotype was not associated with higher mortality but was independently associated with persistent MRSA bacteraemia (OR=5.996, 95% CI 1.438-25.005). To summarise, although hVISA is correlated with persistent bacteraemia, higher mortality in high vancomycin MIC infections could not be explained by the existing hVISA phenotype. Facing persistent bacteraemia under glycopeptide therapy for 7 days, clinicians should consider shifting to an alternative class of antibiotics to treat hVISA infection.

Wang JL ，Lai CH ，Lin HH ，Chen WF ，Shih YC ，Hung CH ... -  《-》