Eu Suk Kim

A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea

Sir, Studies on the molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) have demonstrated their genetic and geographic diversity in comparisons between the community-associated (CA) and hospitalassociated (HA) strains. In addition, it has been suggested that the CA-MRSA found in Korea is genetically different from those found in other regions of the world. – 3 Recently, Kim et al. reported a nationwide survey of CA-MRSA in Korea. We also published an article on the same subject in Korea. Both studies confirmed the unique features of the Korean MRSA strains. Kim et al. designed a prospective sentinel hospital laboratory-based survey from seven hospitals in Korea. After dividing the strains into CA-MRSA and HA-MRSA, 72 isolates from each group were compared. Pathogens, colonizers and an ‘undetermined’ group were all included in the study. However, we have collected isolates from blood, wounds and pus from six hospitals in an effort to exclude possible colonization and contaminants. The enrolled hospitals did not overlap in the two articles. The definitions of CA-MRSA and multidrug resistance (MDR), and the number of antibiotics used in susceptibility testing, were slightly different in comparisons between the two articles. Kim et al. calculated the resistance rate as the number of intermediate and resistance strains over the total number of strains. In contrast, we did not consider ‘intermediate’ as resistance. Finally, we clustered MRSA isolates into representative groups based on genetic backgrounds, and clonal types were redefined according to staphylococcal chromosome cassette mec (SCCmec) type and susceptibilities. Despite these differences, both articles demonstrated similar features of the MRSA in Korea: SCCmec type IVA/ST72/Panton–Valentine leucocidin (PVL)-negative and SCCmec type II or III/ST5 or ST239/ PVL-negative strains were predominant in CA-MRSA and HA-MRSA, respectively. Kim et al. reported that for CA-MRSA, the prevalence of SCCmec type IVA was 43% and the prevalence of ST72 was 35%, and that for HA-MRSA, the prevalence of SCCmec type II or III was 82% and the prevalence of ST5 or ST239 was 86%. Similarly, our data showed that for CA-MRSA, the prevalence of SCCmec type IVA was 53.1% and the prevalence of ST72 was 27.2%, and that for HA-MRSA, the prevalence of SCCmec type II or III was 73.6% and the prevalence of ST5 or ST239 was 73.7%. PVL toxin was rarely identified in either study. In Korea, SCCmec type II or III /ST5 or ST239 was prevalent in HA-MRSA. The articles by Kim et al. and Park et al. elucidated the characteristics of CAand HA-MRSA in Korea. It is interesting that both studies were nationwide studies performed at the same time and had very similar results. We think the data shown in these articles represent the current features of both CAand HA-MRSA in Korea. However, we would like to recommend caution with regard to the conclusion that MDR in CA-MRSA was high (64%), as suggested by Kim et al. Jung et al. also reported that 60.7% of the CA-MRSA isolates were MDR. However, most of their CA-MRSA (82%) were community-onset HA-MRSA cases based on the definition of Kim et al. Another study in Korea showed that ,50% of the strains, among 20 SCCmec type IVA, were MDR when standardized according to the definition of Kim et al. After conforming to the definitions of Kim et al., we re-analysed our data and found that the overall MDR rate, in CA-MRSA, was 51.9%. However, we grouped the clonal types according to their genetic backgrounds and SCCmec type, and found antibiotic susceptibility patterns more distinctly classified (Table 1; modified from Park et al.). For example, most ST72 belonging to B-I were not MDR. B-I, D-I and E-I corresponded to SCCmec type IVA, and most of B-I and D-I were not MDR either. Therefore, the SCCmec type IVA/ST72/PVL-negative clones, the dominant CA-MRSA strains in Korea, were not MDR at least. The clonal types could have the advantage of demonstrating antibiotic susceptibility patterns more precisely than the groups defined by SCCmec only. We agree with Kim et al. and Jung et al. that there were multiple clones of CA-MRSA circulating in communities in Korea and some clones had MDR characteristics similar to HA-MRSA. Even in the dominant SCCmec type IVA in CA-MRSA, our data showed that there would be at least three different groups; however, only 30.2% were MDR. As commented on by Park et al., isolates classified as ‘undetermined’ (46.4%) were all recovered from patients with chronic otitis media; most of them belonged to ST5 or ST239, which was predominant in the HA-MRSA. These findings may explain why the authors concluded that the MDR rate was high in the CA-MRSA. If the subgroup analysis was performed for the pathogen, colonizer and undetermined groups, or the clonal type was used in the analysis, a different conclusion would be expected. In order to confirm the epidemiological characteristics, standardization of study design, classifications and definitions are required. Further study is required to monitor the current trends and detect changes when they occur both locally and worldwide.

Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea.

We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.

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.

Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Isolates in Korea

ABSTRACT We used several molecular typing methods to analyze 196 methicillin-resistant Staphylococcus aureus (MRSA) and 139 methicillin-susceptible S. aureus (MSSA) isolates collected between 1996 and 2005. The sequence type 72 MRSA has increased in frequency in the community in the Republic of Korea and in hospitals in recent years.

Microbiologically and Clinically Diagnosed Vertebral Osteomyelitis: Impact of Prior Antibiotic Exposure

ABSTRACT We retrospectively reviewed medical records to identify the factors that affect the results of culture in patients with pyogenic vertebral osteomyelitis. In multivariate analysis, the presence of paravertebral abscess was associated with positive results of microbiologic culture. Prior antibiotic exposure, especially of longer duration, was strongly associated with negative results.

Clinical Importance and Epidemiology of Quinolone Resistance

The quinolone class of antimicrobial agents is one of most widely used classes of antimicrobial agents in outpatient and inpatient treatment. However, quinolone resistance in gram-positive and gram-negative bacteria has emerged and increased globally. This resistance limits the usefulness of quinolones in clinical practice. The review summarizes mechanisms of quinolone resistance and its epidemiology and implications in the most common clinical settings, urinary tract infections, respiratory tract infections, intraabdominal infections, skin and skin structure infections, and sexually transmitted diseases.

Risk factors for device-associated infection related to organisational characteristics of intensive care units: findings from the Korean Nosocomial Infections Surveillance System.

Device-associated infections (DAIs) have been the major causes of morbidity and mortality of patients in intensive care units (ICUs). This study evaluated the risk factors for DAIs in ICUs. Ninety-six medical or surgical ICUs of 56 hospitals participated in the Korean Nosocomial Infections Surveillance System between July 2007 and June 2008. The occurrence of catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CABSI), and ventilator-associated pneumonia (VAP) were monitored and DAI rates were calculated. Data associated with ICU characteristics were collected and Poisson regression was used for statistical analysis. Rates of CAUTI, CABSI, and VAP were 3.87 per 1000 urinary catheter days, 2.23 per 1000 central line days, and 1.89 per 1000 mechanical ventilator days, respectively. Rates of CAUTI were higher in ICUs in Seoul (P=0.032) and ICUs of major teaching hospitals (P=0.010). The ICUs of university-affiliated hospitals showed lower CAUTI rates (P=0.013). CABSI rates were higher in Seoul (P=0.001) and in medical ICUs (P=0.026). VAP rates were lower in ICUs of hospitals with more than 900 beds compared with hospitals with 400-699 beds (P=0.026). VAP rates were higher in surgical ICUs (P<0.0001) and increased 1.13-fold with each 100-unit increase in beds per infection control professional (P=0.003). The organisational and institutional characteristics of ICUs may influence DAI rates and there is a need for improvement in the incidence of VAP, CAUTI or CABSI.

Association of norB overexpression and fluoroquinolone resistance in clinical isolates of Staphylococcus aureus from Korea

OBJECTIVES Although the prevalence of fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) is known to be higher than in methicillin-susceptible S. aureus (MSSA), the reasons have never been identified. METHODS We randomly selected 115 isolates of S. aureus collected from 10 different hospitals in Korea between June 2009 and May 2011. To investigate the difference in fluoroquinolone resistance mechanisms between MRSA and MSSA, we evaluated gyrA and parC mutations and the relative expression of the multidrug efflux pump genes norA, norB and norC. RESULTS All 62 ciprofloxacin-resistant S. aureus had either gyrA or parC mutations. The S84L mutation of gyrA (59/62, 95.2%) and the S80F mutation of parC (61/62, 98.4%) were the most common. Fifty-eight (93.6%) strains had both the S84L mutation of gyrA and the S80F mutation of parC. Among the 115 isolates, norB overexpression was the most common, occurring in 49 (42.6%) strains. There were only two (1.7%) strains with norA overexpression and none with norC overexpression. Strains overexpressing norB were more common among ciprofloxacin-resistant S. aureus (33/62, 53.2%) than ciprofloxacin-susceptible S. aureus (16/53, 30.2%) (P = 0.013). When we analysed 62 ciprofloxacin-resistant S. aureus strains, those overexpressing norB were more common in ciprofloxacin-resistant MRSA (28/46, 60.9%) than in ciprofloxacin-resistant MSSA (5/16, 31.3%) (P = 0.041). CONCLUSIONS Increased expression of norB can be a factor that contributes to ciprofloxacin resistance in MRSA strains.

Empirical Use of Ciprofloxacin for Acute Uncomplicated Pyelonephritis Caused by Escherichia coli in Communities Where the Prevalence of Fluoroquinolone Resistance Is High

ABSTRACT There is little information about the effectiveness of ciprofloxacin in regions where ciprofloxacin-resistant Escherichia coli is prevalent. This study was conducted to evaluate whether ciprofloxacin is effective as the initial empirical antibiotic for treatment of uncomplicated acute pyelonephritis (APN) due to ciprofloxacin-resistant E. coli. A total of 255 women with clinical diagnoses of uncomplicated APN due to E. coli were enrolled in the emergency department between March 2005 and December 2008. All enrolled patients were initially treated with ciprofloxacin. Patients were followed up 4 to 7 days after the start of therapy and 14 to 21 days after its completion. At the first follow-up visit, ciprofloxacin was changed to the appropriate antibiotic when necessary, depending on the antibiotic susceptibility results. Not only improvement of symptoms and signs but also microbiologic eradication was assessed at each visit. Fifteen percent (39/255) of the E. coli isolates were resistant to ciprofloxacin. There was no statistically significant difference between the clinical cure rates of the ciprofloxacin-susceptible group and the ciprofloxacin-resistant group at the first follow-up (87.0% versus 76.9%, P = 0.135) or the second follow-up (98.6% versus 94.9%, P = 0.177). However, there was a lower microbiologic cure rate in the ciprofloxacin-resistant group than in the ciprofloxacin-susceptible group (92.4% versus 41.7%, P = 0.000) at the first follow-up visit. No complications occurred in the ciprofloxacin-resistant group during the follow-up period. Our findings indicate that ciprofloxacin is an appropriate choice for empirical therapy of uncomplicated APN and has no serious adverse outcomes, if it is tailored appropriately, even for women infected with ciprofloxacin-resistant E. coli.

Viral Load Kinetics of MERS Coronavirus Infection

Middle East respiratory syndrome coronavirus continues to circulate in the Middle East. During a recent outbreak in Korea, changes in MERS coronavirus viral load were determined during the course of illness in 17 patients.