Ten-Year Prevalence Trends of Phenotypically Identified Community-Associated Methicillin-Resistant Staphylococcus aureus Strains in Clinical Specimens
2021; 41(4): 386-393
Ann Lab Med 2018; 38(3): 212-219
Published online May 28, 2018 https://doi.org/10.3343/alm.2018.38.3.212
Copyright © Korean Society for Laboratory Medicine.
Sunjoo Kim, M.D.1, Jung-Hyun Byun, M.D.1,*, Hyunwoong Park, M.D.1, Jaehyeon Lee, M.D.2, Hye Soo Lee, M.D.2, Haruno Yoshida, M.A.3, Akiyoshi Shibayama, M.T.3, Tomohiro Fujita, M.T.3, Yuzo Tsuyuki, M.T.3, and Takashi Takahashi, M.D.3*
1Department of Laboratory Medicine, Gyeongsang National University College of Medicine, Jinju, Korea.
2Department of Laboratory Medicine, Chonbuk National University School of Medicine, Jeonju, Korea.
3Laboratory of Infectious Diseases, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
Correspondence to: Corresponding author: Takashi Takahashi. Laboratory of Infectious Diseases, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Tel: +81-3-5791-6428, Fax: +81-3-5791-6441, email@example.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The molecular characterization of
SDSE isolates were collected from Korea (N=69) from 2012?2016 and Japan (N=71) from 2014?2016. Clinical characteristics,
Median ages were 69 years in Korea and 76 years in Japan. The most common underlying diseases were diabetes and malignancy. Blood-derived isolates comprised 36.2% and 50.7% of Korean and Japanese isolates, respectively; mortality was not different between the two groups (5.8% vs 9.9%,
SDSE infections commonly occurred in elderly persons with underlying diseases. There was a significant difference in the distribution of ST-
SDSE causes skin abscesses, cellulitis, arthritis, bacteremia, pneumonia, meningitis, or intra-abdominal abscesses; it can even cause post-streptococcal glomerulonephritis or rheumatic fever, which are the main sequelae of
Therefore, clinical awareness of SDSE as a virulent pathogen is warranted. The incidence of SDSE infections seems equal to or higher than that of
SDSE infections are more common in elderly patients with underlying comorbidities [2,4,5,7,11]. The
A systematic review of clinical characteristics or molecular epidemiological features of SDSE has not yet been performed in Korea. We report the clinical features and molecular epidemiological findings of SDSE in Korea and compare them with those observed in Japan during similar periods. Furthermore, among erythromycin-resistant
SDSE isolates were collected using the repository at each institution from two different southern geographical areas (Gyeongsang and Jeolla provinces) in Korea between 2012 and 2016 through two tertiary-care hospitals (Gyeongsang National University Hospital [GNUH] in Gyeongsang and Chonbuk National University Hospital in Jeolla), and from three central regions (Tokyo, Saitama, and Chiba prefectures) in Japan between 2014 and 2016 through either two regional hospitals (Kitasato Medical Center [KMS] in Saitama and Mishuku Hospital supported by Federation of National Public Service and Personnel Mutual Aid Associations in Tokyo) or one laboratory center (Sanritsu Co., Ltd. in Chiba). The isolates with the possibility of true infection were consecutively collected, and repeated isolates from the same patients were excluded. The institutions in both countries sent all the isolates to a laboratory (Gyeongsang National University College of Medicine/Kitasato Institute for Life Sciences) for further genetic analysis. Bacterial identification was conducted using an API-20 Strep or Vitek-2 system (bioMerieux Inc., Marcy l'Etoile, France) and was confirmed by 16S rRNA sequencing. This identification was confirmed if the isolate sequence had ≥98.7% similarity to the 16S rRNA sequence of SDSE type strain NCFB 1356(T). All isolates were stored at −70℃ to −80℃ before being processed for further evaluation. The clinical characteristics, including underlying diseases, infection sites, surgical intervention for treatment, and mortality were reviewed using the patients' medical charts. Infection-associated death was defined as mortality within three weeks of disease onset .
Institutional Review Boards at the corresponding institutions (GNUH and KMS) examined and approved this study protocol (approval number GNUH 2015-10-002 and 27-58 from each institution) before starting the investigation.
An antimicrobial susceptibility test was performed using 14 different antimicrobial agents, including β-lactams, tetracyclines, macrolides/lincosamides, and fluoroquinolone, to evaluate antimicrobial resistance levels by broth microdilution test using either the MICroFAST or MicroScan WalkAway System (Beckman Coulter, Inc., Brea, CA, USA) according to the CLSI guidelines [17,18] with the same ATCC strain (Group G strain D166B) as the quality control. In Japan, tetracycline was changed to minocycline as the screening antimicrobial in 2015. Fifty-six isolates from Japan and all Korean isolates were tested with minocycline.
Antimicrobial resistance determinants, such as
Statistical analysis was performed using MedCalc Statistical Software version 17.6 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2017). The Kolmogorov-Smirnov test was used to test normal distribution. To compare two non-normally distributed groups, the Mann-Whitney U test was used. Fisher's exact probability test (two-sided) was used for categorical variables.
Demographic information and clinical manifestations of SDSE infections in Korea and Japan are shown in Table 1. We observed several significant differences between the two countries. Median age was 69 years in Korea and 76 years in Japan (
The STs and
Among the 71 Japanese isolates, there were 29 different combinations of ST-
The distribution of the common
There was no statistically significant difference in antimicrobial resistance rates between the two countries (
Resistance rates to erythromycin, azithromycin, clindamycin, and minocycline were 34.8%, 34.8%, 17.4%, and 30.4%, respectively, for Korean isolates (Table 2). Several ST-
Resistance rates to erythromycin, azithromycin, clarithromycin, clindamycin, tetracycline, and minocycline were 28.2% (No. of examined isolates=71), 32.1% (N=56), 13.3% (N=15), 14.1% (N=71), 26.7% (N=15), and 21.4% (N=56), respectively, for Japanese isolates (Table 3).
Among the 20 erythromycin-resistant strains,
Among the 10 isolates resistant to clindamycin,
The 50% minimum inhibitory concentrations (MIC50) of erythromycin, clindamycin, and minocycline were ≤0.12 µg/mL, ≤0.12 µg/mL, and 0.5 µg/mL, and the MIC90 of these antimicrobial agents were >2 µg/mL, >1 µg/mL, and >4 µg/mL, respectively, for both Korean and Japanese isolates. Fluoroquinolone-resistant isolates (N=5) were identified only in Japan. None of the tested SDSE isolates from either country were resistant to β-lactams.
Although there have been sporadic case reports regarding SDSE infections, there was no systematic report in Korea yet. There are two SDSE bacteremia cases originated from endocarditis and cellulitis, respectively, in Korea . The
Recently, Takahashi et al  reported the distribution of CC17 (
SDSE infections seemed more invasive in Japan because the proportion of blood-derived isolates (36.2% vs 50.7%) was relatively higher in Japan. SDSE caused more wound infections in Korea (46.4% vs 11.3%) and more respiratory tract infections in Japan (4.4% vs 23.9%). The prevalence of sepsis was similar (10.2% vs 7.0%) between the two countries, whereas cellulitis was more common in Korea (44.9% vs 28.2%). More than half of the patients visited the hospitals through the emergency department. Surgical intervention was more common in Korea (37.7% vs 16.9%) because wound infections comprised a larger portion of cases. The most common underlying comorbidities in both countries were diabetes and malignancy. The higher median age (69 years vs 76 years) for Japanese patients might be the reason for the higher proportion of elderly patients in Japan. Mortality in this study was lower than that observed in other studies [1,10,11] because we included non-invasive cases.
More diverse combinations of ST-
The distribution of common
The prevalent invasive
Antimicrobial resistance rates significantly increased compared with those in 2007 in Korea—from 9.4% to 34.8% for erythromycin and from 3.1% to 17.4% for clindamycin . Antimicrobial resistance rates to erythromycin, clindamycin, and minocycline were comparable between each country. In addition, MIC50 and MIC90 for these antibiotics were equivalent. However, the frequency of antimicrobial resistance determinants was quite different.
Most of the minocycline-resistant isolates harbored the
In conclusion, SDSE commonly caused infections in the elderly who had diabetes or malignancy in both Korea and Japan. The proportion of bacteremia and mortality was slightly higher in Japan. The prevalent
No potential conflicts of interest relevant to this article were reported.
This study was supported in part by biomedical research institute fund (GNUHBIF-2016-0003) from the GNUH, and Development Fund Foundation, Gyeongsang National University, 2015 to Sunjoo Kim. This publication made use of the
eBURST analysis of
Demographics and clinical manifestations of infectious diseases due to
|Demographics and clinical manifestations||Korean patients (N=69)||Japanese patients (N=71)|
|N (%)||N (%)|
|Sex, male||41 (59.4)||39 (54.9)||0.61|
|Age, median (IQR)||69 (56–83)||76 (65–84)||0.0002|
|Emergency department||40 (58.0)||39 (54.9)||0.73|
|Diabetes||21 (30.4)||15 (21.1)||0.24|
|Malignancy||12 (17.4)||20 (28.2)||0.16|
|Surgical intervention||26 (37.7)||12 (16.9)||0.008|
|Blood||25 (36.2)||36 (50.7)||0.09|
|Pus||32 (46.4)||8 (11.3)||0.00005|
|Sputum/throat||3 (4.4)||17 (23.9)||0.001|
|Urine/vagina||5 (7.3)||6 (8.5)||1.0|
|Synovial fluid||3 (4.4)||1 (1.4)||0.36|
|Others||1 (1.5)||3 (4.2)||0.62|
|Mortality||4 (5.8)||7 (9.9)||0.53|
|Sepsis||7 (10.2)||5 (7.0)||0.56|
|Cellulitis||31 (44.9)||20 (28.2)||0.05|
|Septic arthritis||10 (14.5)||6 (8.5)||0.30|
|Other||21 (30.4)||40 (56.3)||0.002|
The sequence types (STs) and
|ST||Antibiotic resistance||Antibiotic resistance genes|
The sequence types (STs) and
|ST||Antibiotic resistance||Antibiotic resistance genes|