Effects of inappropriate empirical antibiotic therapy on mortality in patients with healthcare-associated methicillin-resistant Staphylococcus aureus bacteremia: a propensity-matched analysis.

BACKGROUND: The purported value of empirical therapy to cover methicillin-resistant Staphylococcus aureus (MRSA) has been debated for decades. The purpose of this study was to evaluate the effects of inappropriate empirical antibiotic therapy on clinical outcomes in patients with healthcare-associated MRSA bacteremia (HA-MRSAB). METHODS: A prospective, multicenter, observational study was conducted in 15 teaching hospitals in the Republic of Korea from February 2010 to July 2011. The study subjects included adult patients with HA-MRSAB. Covariate adjustment using the propensity score was performed to control for bias in treatment assignment. The predictors of in-hospital mortality were determined by multivariate logistic regression analyses. RESULTS: In total, 345 patients with HA-MRSAB were analyzed. The overall in-hospital mortality rate was 33.0 %. Appropriate empirical antibiotic therapy was given to 154 (44.6 %) patients. The vancomycin minimum inhibitory concentrations of the MRSA isolates ranged from 0.5 to 2 mg/L by E-test. There was no significant difference in mortality between propensity-matched patient pairs receiving inappropriate or appropriate empirical antibiotics (odds ratio [OR] = 1.20; 95 % confidence interval [CI] = 0.71-2.03). Among patients with severe sepsis or septic shock, there was no significant difference in mortality between the treatment groups. In multivariate analyses, severe sepsis or septic shock (OR = 5.45; 95 % CI = 2.14-13.87), Charlson's comorbidity index (per 1-point increment; OR = 1.52; 95 % CI = 1.27-1.83), and prior receipt of glycopeptides (OR = 3.24; 95 % CI = 1.08-9.67) were independent risk factors for mortality. CONCLUSION: Inappropriate empirical antibiotic therapy was not associated with clinical outcome in patients with HA-MRSAB. Prudent use of empirical glycopeptide therapy should be justified even in hospitals with high MRSA prevalence.

Clinical implications of cefazolin inoculum effect and ß-lactamase type on methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Cefazolin is a common antibiotic for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Type A or C ß-lactamase-producing MSSA frequently shows the cefazolin inoculum effect (CIE). However, the clinical implication of the CIE for MSSA bacteremia is obscure. METHODS: MSSA bacteremic patients treated with cefazolin were included in a retrospective cohort study. The blaZ gene of the isolates was sequenced to identify the type of ß-lactamase. The patients whose isolates showed a ≥4-fold increase in cefazolin, the minimal inhibitory concentration (MIC) at the high inoculum (∼5×10(7) CFU/ml), were assigned to the CIE-positive group and the remainder to the CIE-negative group. Treatment failure was assessed at 12 weeks after cefazolin was initiated. RESULTS: A total of 113 MSSA bacteremic patients were included. Among the 113 isolates, 57.5% showed the CIE and 77.9% carried the blaZ gene; type A ß-lactamase was 15.0% and type C was 40.7%. Persistent bacteremia was more common in the CIE-positive group (9% vs. 0%, p=0.04). Treatment failure rates were higher in the CIE-positive group with high bacterial burden infection, but the difference was not significant (48% vs. 25%, p=0.13). There was no significant difference of failure between groups with high-inoculum MIC ≥16 and ≤1 µg/ml (13% vs. 5%, p=0.31). In the multivariable analysis, underlying cardiovascular diseases, pneumonia, osteoarticular infections, and endocarditis were significant risk factors for treatment failure and the CIE was not significantly associated with treatment failure. CONCLUSION: The CIE might be associated with persistent bacteremia if cefazolin is used for MSSA bacteremia with a high burden of infections. However, the sites of infections are more important factors for the clinical outcome than the CIE.

Multicenter prospective observational study of the comparative efficacy and safety of vancomycin versus teicoplanin in patients with health care-associated methicillin-resistant Staphylococcus aureus bacteremia.

The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 µg/ml (MIC50 and MIC90, 1.5 µg/ml), and the TEC MIC ranged from 0.5 to 8 µg/ml (MIC50, 3 µg/ml; MIC90, 6 µg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.

Evaluation of a triple-drug combination for treatment of experimental multidrug-resistant pneumococcal meningitis.

To evaluate the therapeutic efficacy of ceftriaxone + vancomycin + rifampicin (CVR) in the treatment of pneumococcal meningitis caused by a multidrug-resistant strain, single-drug regimens (ceftriaxone 100 mg/kg, rifampicin 15 mg/kg, or vancomycin 20 mg/kg), double-drug regimens (ceftriaxone + vancomycin [CV] and ceftriaxone + rifampicin [CR]) and a triple-drug combination (CVR) with or without dexamethasone were compared in a rabbit meningitis model. Meningitis was induced by a highly penicillin-resistant (MIC 2 mg/l) and ceftriaxone-resistant (MIC 4 mg/l) pneumococcal strain. Final therapeutic efficacy was evaluated by the bacterial concentration at 24 h, and the bacterial killing rate was also evaluated. All combination regimens were superior to ceftriaxone or vancomycin single-drug regimens with regard to sterilisation of CSF and bacterial killing rate. Rifampicin was as effective as combination regimens. Regardless of dexamethasone, therapeutic efficacy of CVR and CR were superior to that of CV. CVR showed comparable therapeutic efficacy to CR. Data suggested that CVR would not have additional therapeutic benefit over CR during the initial 24 h of treatment.