Pyoeng Gyun Choe

Severe fever with thrombocytopenia syndrome, South Korea, 2012.

We report a retrospectively identified fatal case of severe fever with thrombocytopenia syndrome (SFTS) in South Korea from 2012. SFTS virus was isolated from the stored blood of the patient. Phylogenetic analysis revealed this isolate was closely related to SFTS virus strains from China and Japan.

One‐year adherence to clinic visits after highly active antiretroviral therapy: a predictor of clinical progress in HIV patients

Objective.  To determine whether adherence to clinic visits early after initiation of highly active antiretroviral therapy (HAART) is predictive of long‐term clinical outcome.

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.

Is Cefazolin Inferior to Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia?

ABSTRACT About 20% of methicillin-susceptible Staphylococcus aureus (MSSA) isolates have a substantial inoculum effect with cefazolin, suggesting that cefazolin treatment may be associated with clinical failure for serious MSSA infections. There are no well-matched controlled studies comparing cefazolin with nafcillin for the treatment of MSSA bacteremia. A retrospective propensity-score-matched case-control study was performed from 2004 to 2009 in a tertiary care hospital where nafcillin was unavailable from August 2004 to August 2006. The cefazolin group (n = 49) included MSSA-bacteremic patients treated with cefazolin during the period of nafcillin unavailability, while the nafcillin group (n = 84) comprised those treated with nafcillin. Treatment failure was defined as a composite outcome of a change of antibiotics due to clinical failure, relapse, and mortality. Of 133 patients, 41 patients from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment failure rates were not significantly different at 4 or 12 weeks (10% [4/41] versus 10% [4/41] at 4 weeks [P > 0.99] and 15% [6/41] versus 15% [6/41] at 12 weeks [P > 0.99]). Cefazolin treatment was interrupted less frequently than nafcillin treatment due to drug adverse events (0% versus 17%; P = 0.02). Cefazolin had clinical efficacy similar to that of nafcillin and was more tolerable than nafcillin for the treatment of MSSA bacteremia.

Should HLA-B*5701 Screening Be Performed in Every Ethnic Group before Starting Abacavir?

Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans.

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.

Genetic Factors Influencing Severe Atazanavir-Associated Hyperbilirubinemia in a Population with Low UDP-Glucuronosyltransferase 1A1*28 Allele Frequency

BACKGROUND High prevalence of severe atazanavir-associated hyperbilirubinemia in Asians with low prevalence of the UDP-glucuronosyltransferase (UGT)1A1*28 polymorphism suggests the importance of genetic factors other than UGT1A1*28 for atazanavir-associated hyperbilirubinemia in these populations. METHODS Serum bilirubin levels were measured in 129 Korean human immunodeficiency virus-infected patients 3 months after initiation of atazanavir (400 mg per day) with good adherence to medication. The multidrug resistance gene 1 (MDR1) C3435T and G2677T/A variations and UGT1A1*6 and *28 were examined by direct sequencing of DNA from peripheral whole blood samples. The associations between genetic polymorphisms and severe (grade 3-4) hyperbilirubinemia were evaluated using multivariate logistic regression analysis including demographic and clinical variables. RESULTS The median patient age was 39 years (interquartile range, 34-51 years), and 91% were men. At baseline, the median CD4 cell count was 261 cells/microL (interquartile range, 181-405 cells/microL). Severe hyperbilirubinemia was detected in 27 patients (21%). The independent risk factors for severe hyperbilirubinemia were low baseline CD4 cell count (adjusted odds ratio per 10 cells/microL increase, 0.97; 95% confidence interval, 0.94-0.99), UGT1A1*28 (adjusted odds ratio, 4.15; 95% confidence interval, 1.46-11.84), and MDR1 G2677T/A (adjusted odds ratio, 9.65; 95% confidence interval, 1.09-85.61). Of 19 patients with wild-type alleles for both MDR1 2677 and UGT1A1*28, none developed severe hyperbilirubinemia. CONCLUSION The MDR1 G2677T/A variation and UGT1A1*28 are independent risk factors for severe atazanavir-associated hyperbilirubinemia in Korean human immunodeficiency virus-infected patients.

Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015.

Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.

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.

Tuberculosis manifested by immune reconstitution inflammatory syndrome during HAART.

The proportion of tuberculosis manifested by immune reconstitution inflammatory syndrome (IRIS) after HAART has not been established. We describe the incidence and clinical features of tuberculosis manifested by IRIS after HAART in an intermediate tuberculosis burden area. The findings suggest that a significant proportion of the tuberculosis occurring early after starting HAART is manifested by IRIS.