Younghee Jung

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.

Characterization of two new genes, vgaD and vatG, conferring resistance to streptogramin A in Enterococcus faecium

ABSTRACT We characterized two new streptogramin A resistance genes from quinupristin-dalfopristin-resistant Enterococcus faecium JS79, which was selected from 79 E. faecium isolates lacking known genes encoding streptogramin A acetyltransferase. A 5,650-bp fragment of HindIII-digested plasmid DNA from E. faecium JS79 was cloned and sequenced. The fragment contained two open reading frames carrying resistance genes related to streptogramin A, namely, genes for an acetyltransferase and an ATP efflux pump. The first open reading frame comprised 648 bp encoding 216 amino acids with a predicted left-handed parallel β-helix domain structure; this new gene was designated vatG. The second open reading frame consisted of 1,575 bp encoding 525 amino acids with two predicted ATPase binding cassette transporters comprised of Walker A, Walker B, and LSSG motifs; this gene was designated vgaD. vgaD is located 65 bp upstream from vatG, was detected together with vatG in 12 of 179 quinupristin-dalfopristin-resistant E. faecium isolates, and was located on the same plasmid. Also, the 5.6-kb HindIII-digested fragment which was observed in JS79 was detected in nine vgaD- and vatG-containing E. faecium isolates by Southern hybridization. Therefore, it was expected that these two genes were strongly correlated with each other and that they may be composed of a transposon. Importantly, vgaD is the first identified ABC transporter conferring resistance to streptogramin A in E. faecium. Pulsed-field gel electrophoresis patterns and sequence types of vgaD- and vatG-containing E. faecium isolates differed for isolates from humans and nonhumans.

Impact of area under the concentration–time curve to minimum inhibitory concentration ratio on vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteraemia

There have been few clinical studies on the association between the vancomycin 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. To examine this association and to establish a suitable cut-off value for AUC24/MIC, a multicentre prospective observational study was conducted in patients with MRSA bacteraemia. Data were collected on all patients aged ≥18 years with MRSA bacteraemia treated with vancomycin for ≥72 h without dialysis. The MIC was determined by broth microdilution (BMD) and Etest. Treatment failure was defined as (i) 30-day mortality, (ii) persistent bacteraemia (≥7 days) and (iii) recurrence (≤30 days after completion of therapy). AUC24 was estimated by a Bayesian approach based on individual vancomycin concentrations. The AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by Classification and Regression Tree (CART) analysis. In total, 117 patients were enrolled, among which vancomycin treatment failure occurred in 38 (32.5%). In univariate analysis, high vancomycin MIC and low trough levels were unrelated to treatment outcomes. In the CART analysis, low vancomycin AUC24/MIC [<392.7 (BMD) and <397.2 (Etest)] was associated with treatment failure. In multivariate analysis, low AUC24/MIC was a risk factor for treatment failure [adjusted odds ratio (aOR)=3.50, 95% confidence interval (CI) 1.39-8.82 by BMD; aOR=5.61, 95% CI 2.07-15.24 by Etest]. AUC24/MIC is associated with vancomycin treatment outcomes in MRSA bacteraemia, and seeking individualised AUC24/MIC ratios above target (>400) may improve treatment outcomes.

Differences in characteristics between healthcare-associated and community-acquired infection in community-onset Klebsiella pneumoniae bloodstream infection in Korea

BackgroundHealthcare-associated (HCA) infection has emerged as a new epidemiological category. The aim of this study was to evaluate the impact of HCA infection on mortality in community-onset Klebsiella pneumoniae bloodstream infection (KpBSI).MethodsWe conducted a retrospective study in two tertiary-care hospitals over a 6-year period. All adult patients with KpBSI within 48 hours of admission were enrolled. We compared the clinical characteristics of HCA and community-acquired (CA) infection, and analyzed risk factors for mortality in patients with community-onset KpBSI.ResultsOf 553 patients with community-onset KpBSI, 313 (57%) were classified as HCA- KpBSI and 240 (43%) as CA-KpBSI. In patients with HCA-KpBSI, the severity of the underlying diseases was higher than in patients with CA-KpBSI. Overall the most common site of infection was the pancreatobiliary tract. Liver abscess was more common in CA-KpBSI, whereas peritonitis and primary bacteremia were more common in HCA-KpBSI. Isolates not susceptible to extended-spectrum cephalosporin were more common in HCA- KpBSI than in CA-KpBSI (9% [29/313] vs. 3% [8/240]; p = 0.006). Overall 30-day mortality rate was significantly higher in HCA-KpBSI than in CA-KpBSI (22% [70/313] vs. 11% [27/240]; p = 0.001). In multivariate analysis, high Charlson’s weighted index of co-morbidity, high Pitt bacteremia score, neutropenia, polymicrobial infection and inappropriate empirical antimicrobial therapy were significant risk factors for 30-day mortality.ConclusionsHCA-KpBSI in community-onset KpBSI has distinctive characteristics and has a poorer prognosis than CA-KpBSI, but HCA infection was not an independent risk factor for 30-day mortality.

agr Dysfunction Affects Staphylococcal Cassette Chromosome mec Type-Dependent Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia

ABSTRACT Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea.

Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison with bacteremia caused by Enterobacteriaceae

BackgroundThis study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis.MethodsA retrospective case–control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia.ResultsSixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%).ConclusionsNosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.

Severe Form of Persistent Thebesian Veins Presenting as Ischemic Heart Disease

Coronary artery fistula is a rare congenital anomaly. Most patients with this anomaly are asymptomatic, but some may develop heart failure, myocardial ischemia or arrhythmias. We report a case of a patient who presented with myocardial ischemia secondary to persistent Thebesian veins. Coronary angiography demonstrated a marked capillary blush draining into the left ventricular cavity through multiple microfistulae from the left anterior descending artery, left circumflex artery and right coronary artery. The patient was discharged without chest pain and was medically maintained with a beta-blocker and angiotensin converting enzyme inhibitor.

Sentinel Surveillance and Molecular Epidemiology of Multidrug Resistance Bacteria

The global emergence and spread of multidrug resistant bacterial infections in communities and hospitals has become an important issue in public health. The resistance rate of gram-positive cocci to vancomycin and the resistance rate of several gram-negative bacilli against cefotaxime and carbapenem have been continuously increasing. Surveillance of antimicrobial resistance is essential for providing information on the magnitude of and trend in multidrug resistance. Therefore, beginning 2011, more robust and effective management is to be legally required for six multidrug-resistant bacteria that have been linked to healthcare-related infections: vancomycin-resistant Staphylococcus aureus (VRSA), vancomycinresistant enterococci (VRE), methicillinresistant S. aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MRPA), multidrug-resistant Acinetobacter baumannii (MRAB), and carbapenem-resistant Enterobactericeae (CRE). We have also performed laboratory-based sentinel surveillance for VRSA/VISA since 2002 and carbapenemase-producing Enterobacteriaceae since November, 2010. This article reviews the national surveillance programs, and molecular epidemiology of multidrug-resistant bacteria. (Korean J Clin Microbiol 2012;15:43-48)

Erratum for Kim et al., inappropriate continued empirical vancomycin use in a hospital with a high prevalence of methicillin-resistant Staphylococcus aureus.

Nak-Hyun Kim, Hei Lim Koo, Pyoeng Gyun Choe, Shinhye Cheon, Moonsuk Kim, Myung Jin Lee, Younghee Jung, Wan Beom Park, Kyoung-Ho Song, Eu Suk Kim, Ji Hwan Bang, Hong Bin Kim, Sang Won Park, Nam Joong Kim, Myoung-don Oh, Eui Chong Kim Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Infection Control Service, Seoul National University Hospital, Seoul, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea