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.

Trends of Antibiotic Consumption in Korea According to National Reimbursement Data (2008-2012): A Population-Based Epidemiologic Study.

This study determined the trends in the quantities and patterns of nationwide antibiotic consumption in the Republic of Korea (ROK).This nationwide descriptive epidemiological study was conducted in the ROK between 2008 and 2012. The quantities and patterns of total systemic antibiotic prescriptions were analyzed using National Health Insurance claims data collected through the Health Insurance Review and Assessment service. Data concerning systemic antibiotics were collected using measurement units of the defined daily dose (DDD) per 1000 people per day according to the Anatomical Therapeutic Chemical classification.Over the 5-year study period, the annual consumption of systemic antibiotics ranged from 21.68 to 23.12 DDD per 1000 people per day. Outpatient antibiotic use accounted for 80.9% of total consumption. A regression model with autoregressive errors showed significant increased consumption of major antibiotic subgroups, including 3rd-generation cephalosporins, carbapenems, and glycopeptides (P < 0.001). However, the antibiotic use of 1st- (P = 0.003), 2nd- (P = 0.004), and 3rd-generation (P = 0.018) cephalosporins among patients who underwent surgery under monitoring by the antimicrobial stewardship programs for perioperative prescription was significantly lower than in those who underwent surgery without monitoring programs. In time-series analysis, total antibiotic consumption demonstrated significant seasonality (P < 0.001).The consumption of broad-spectrum antibiotics was noted to have increased in the ROK from 2008 to 2012, providing a possible explanation for the changing epidemiology of multidrug resistance. Larger prospective studies are needed to investigate the impact on public health of monitoring programs of perioperative antibiotic usage.

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.

Predictors of persistent methicillin-resistant Staphylococcus aureus bacteraemia in patients treated with vancomycin.

OBJECTIVES: The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) coupled with an increase in vancomycin use have induced vancomycin tolerance in MRSA, adversely affecting the outcome of MRSA bacteraemia. This study aimed to identify predictors of persistent MRSA bacteraemia (PMRSAB) in patients treated with vancomycin. METHODS: A retrospective, case-control study was performed at a university hospital in Korea from January 2006 to February 2009. Subjects included 96 patients who had MRSA bacteraemia and received vancomycin under therapeutic drug monitoring. We compared the clinical characteristics, management and outcomes of cases with PMRSAB (>or=7 days, n = 31) with controls with non-PMRSAB (

Control of extended-spectrum {beta}-lactamase-producing Klebsiella pneumoniae using a computer-assisted management program to restrict third-generation cephalosporin use.

OBJECTIVES: The aim of this study was to evaluate the control of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and antimicrobial resistance through a computerized antibiotic control program. METHODS: An ambidirectional intervention study was conducted at a 750-bed university hospital in Korea from February 2004 to April 2006. In November 2004, hospital-wide restriction of third-generation cephalosporin use was integrated into a pre-existing computerized antibiotic prescription program that included an approval system for 15 antimicrobials. The proportions of ESBL-producing K. pneumoniae and other multidrug-resistant clinical isolates were compared during three phases (9 months per phase): Phase I (pre-intervention), Phase II (intensive-intervention) and Phase III (maintenance). RESULTS: Third-generation cephalosporin use decreased significantly from 103.2 to 84.9 antibiotic use density (AUD, defined daily dose/1000 patient-days) between Phase I and Phase II (P< 0.05), whereas use of carbapenems and beta-lactam/beta-lactamase inhibitors increased from 14.5 to 18.2 AUD and from 53.3 to 62.6 AUD, respectively. The proportion of ESBL-producing K. pneumoniae isolates increased significantly from 8.1% (47/578) in Phase I to 32.0% (188/587) in Phase II, and then decreased significantly to 20.6% (97/470) in Phase III (P < 0.05). In addition, the proportions of imipenem- or piperacillin/tazobactam-resistant Pseudomonas aeruginosa and Acinetobacter baumannii isolates decreased significantly over the same period (P < 0.05). CONCLUSIONS: The computerized antibiotic control program appears to be an effective tool for modifying antibiotic consumption, which may in turn prevent the spread of resistant pathogens.