Current status of multidrug-resistant bacteria

The dissemination of multidrug-resistant (MDR) pathogen is of major public health concern as it leads to increased mortality rate, length of hospital stays, and medical expenses.Current Concepts: Korean Government enacted an Infectious Disease Control and Prevention Act in 2009, and 6 MDR bacteria including methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus (VRSA), vancomycin-resistant enterococci, multidrug-resistant Pseudomonas aeruginosa, multidrug-resistant Acinetobacter baumannii, and carbapenem-resistant Enterobacterales (CRE) have been legally declared as infectious diseases. According to the amendment of the Infectious Disease Control and Prevention Act in 2020, CRE and VRSA were classified as class 2 infectious diseases, and all cases of CRE and VRSA should be reported to the Korea Disease Control and Prevention Agency (KDCA). Methicillin-resistant S. aureus, vancomycin-resistant enterococci, multidrug-resistant P. aeruginosa, and multidrug-resistant A. baumannii were classified as class 4 infectious diseases, and cases that occur need to be monitored at KDCA-designated sentinel hospitals to prevent further dissemination.Discussion and Conclusion: In this review, the current antimicrobial resistance status of six types of MDR bacteria, legally declared as infectious diseases, was investigated.. The Korean government is operating national antimicrobial resistance surveillance systems such as the Korean Antimicrobial Resistance Monitoring System and Korean Global Antimicrobial Surveillance System, as a foundation for preventing the spread of antimicrobial resistance. Certain steps need to be taken, such as establishing a surveillance system for antimicrobial usages, strengthening antimicrobial stewardship and infection control systems, and developing new antimicrobials in order for us to achieve the national goal.

Clinical and Microbiological Risk Factors for Community-Associated Clostridioides difficile Infections / 대한임상미생물학회지

Background@#The incidence of community-associated (CA) Clostridioides difficile infection (CDI) has increased in Korea. In this study, we evaluated CA-CDI risk factors in terms of clinical features and ribotype considering its region-specific molecular epidemiology. @*Methods@#A retrospective case-control study was performed on two groups of CDI patients:127 subjects with CA-CDI and 265 subjects with healthcare-associated (HA)-CDI. Risk factors for CA-CDI were evaluated in terms of clinical and microbiological features such as toxin type and ribotype. @*Results@#A comparison of the two groups of CDI patients revealed that inflammatory bowel disease, diarrhea, abdominal pain, and fever were more closely associated with CA-CDI. The toxin types and ribotypes of C. difficile were similar between the two groups. After adjusting for variables, no risk factors were identified for CA-CDI compared with HA-CDI. @*Conclusion@#Specific risk factors for CA-CDI were not identified in this study.

Clinical and Microbiological Risk Factors for Severe Clostridioides difficile Infections / 대한임상미생물학회지

Background@#There has been a marked increase in the mortality rate associated with Clostridioides difficile infection (CDI) globally since 2003, with the emergence of binary toxinproducing ribotype 027 strains. However, the molecular epidemiology of C. difficile shows regional differences and ribotype 027 is not common in Korea. In this study, the risk factors for severe CDI were evaluated, while considering the region-specific molecular epidemiology. @*Methods@#A retrospective case-control study was performed. Cases (n = 149) included patients with severe CDI or severe complicated CDI. Controls (n = 155) consisted of patients with nonsevere CDI. @*Results@#Advanced age (odds ratio [OR] = 1.017, P = 0.0358), a history of chemotherapy (OR = 2.695, P = 0.0464), and ribotype 002 (OR = 3.406, P = 0.0231) were statistically significant factors associated with severe CDI in a multivariate analysis. @*Conclusion@#Ribotype 002 was found to be a significant risk factor for severe CDI in this study.Therefore, the surveillance of C. difficile ribotypes is recommended to monitor the spread of high-risk clones.

Epidemiological Study of an Outbreak of KPC-2-producing Klebsiella pneumoniae in a Tertiary Hospital in Korea / 대한임상미생물학회지

Background@#The prevalence of carbapenemase-producing Enterobacteriaceae (CPE), especially the KPC-2-producing Klebisella pneumoniae, is rapidly increasing and becoming a menace to global public health. This study aims to present the molecular epidemiology of the KPC-2-producing K. pneumoniae isolates emerged in a tertiary hospital in South Korea and describe its clinical significance. @*Methods@#This study included carbapenem-resistant K. pneumoniae isolates collected from a tertiary hospital from April to December in 2018. Antimicrobial susceptibility of K. pneumoniae isolates was tested using disk diffusion method. PCR and DNA sequence analyses were performed to identify the resistance genotype. In addition, the molecular epidemiology was investigated using pulsed-field gel electrophoresis (PFGE) and multilocus sequencing typing (MLST). @*Results@#Total 100 KPC-2-producing K. pneumoniae isolates were collected, which were mainly classified into two pulsotypes according to the XbaI restriction digestion pattern by PFGE analysis (pulsotype A, n = 31; pulsotype B, n = 63). The isolates exhibiting pulsotype A belonged to ST395 and the remaining isolates exhibiting pulsotype B were attributed to ST307 by MLST analysis. @*Conclusion@#This study investigated clinical information and molecular bacterial profiles for KPC-2-producing K. pneumoniae isolates. These findings indicate that the proper infection control activities are needed to prevent the spread of multidrug-resistant organisms such as CPE, which could cause high mortality in clinical field.

Performance Evaluation of the Newly Developed BD Phoenix NMIC-500 Panel Using Clinical Isolates of Gram-Negative Bacilli

BACKGROUND: The emergence of carbapenem resistance among gram-negative bacilli (GNB), mediated by carbapenemase production, has necessitated the development of a simple and accurate device for detecting minimum inhibitory concentrations (MICs) and resistance mechanisms, especially carbapenemase production. We evaluated the performance of the BD Phoenix NMIC-500 panel (BD Diagnostic Systems, Sparks, MD, USA) for antimicrobial susceptibility testing (AST) and carbapenemase-producing organism (CPO) detection. METHODS: We used 450 non-duplicate clinical GNB isolates from six general hospitals in Korea (409 Enterobacteriaceae and 41 glucose non-fermenting bacilli [GNFB] isolates). AST for meropenem, imipenem, ertapenem, ceftazidime, and ceftazidime/avibactam, and CPO detection were performed using the Phoenix NMIC-500 panel. Broth microdilution was used as the reference method for AST. The rates of categorical agreement (CA), essential agreement (EA), minor error (mE), major error (ME), and very major error (VME) were calculated in each antimicrobial. In addition, PCR and sequencing were performed to evaluate the accuracy of CPO detection by the BD Phoenix NMIC-500 panel, and the rate of correct identification was calculated. RESULTS: The CA rates were >90% for all antimicrobials tested with the Enterobacteriaceae isolates, except for imipenem (87.2%). The GNFB CA rates ranged from 92.7% to 100% for all antimicrobials. The ME rates were 1.7% for Enterobacteriaceae and 0% for GNFB. The panel identified 97.2% (243/250) of the carbapenemase-producing isolates. CONCLUSIONS: The BD Phoenix NMIC-500 panel shows promise for AST and CPO detection.

Differences in Antimicrobial Resistance Phenotypes by the Group of CTX-M Extended-Spectrum β-Lactamase / 대한임상미생물학회지

BACKGROUND: Escherichia coli and Klebsiella pneumoniae clinical isolates producing CTX-M extendedspectrum β-lactamases (ESBLs) were assessed for antimicrobial resistance phenotypes varied by group of enzymes. METHODS: A total of 1,338 blood isolates, including 959 E. coli and 379 K. pneumoniae, were studied. All the strains were collected between January and July 2017 from eight general hospitals in South Korea. The species were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined by disk diffusion methods and ESBL phenotypes by double-disk synergy tests using disks containing cefotaxime, ceftazidime, cefepime, aztreonam, and clavulanic acid (CA). The genes for β-lactamases were identified by PCR and sequencing. RESULTS: Of total microbes, 31.6% (303/959) E. coli and 24.0% (91/379) K. pneumoniae were resistant to cefotaxime and 28.1% (269/959) E. coli and 20.1% (76/379) K. pneumoniae were CTX-M-type ESBL producers. Among the detected CTX-M ESBLs, 58.0% (156/269) in E. coli and 86.8% (66/76) in K. pneumoniae belonged to group 1, 46.8% (126/269) in E. coli and 14.5% (11/76) in K. pneumoniae were group 9. Ten E. coli and one K. pneumoniae isolates co-produced both groups of CTX-M ESBL. The group 1 CTX-M producers had a higher level of resistance to cefotaxime, ceftazidime, cefepime, and aztreonam and exhibited stronger synergistic activities when combined with CA compared to group 9. CONCLUSION: ESBL phenotypes differ by CTX-M ESBL group and phenotype testing with drugs including 4th generation cephalosporins and monobactams is critical for screening CTX-M-producers with better sensitivity.

First Case of Trueperella bernardiae Bacteremia in an Immunocompromised Patient in Korea

No abstract available.

Performance Evaluation of Newly Developed Korean Antimicrobial Susceptibility Testing Panels for MicroScan System Using Clinical Isolates from Teaching Hospitals in Korea / 대한임상미생물학회지

BACKGROUND: Antimicrobial resistant continues to pose a threat to public health. Therefore, rapid and accurate antimicrobial susceptibility testing is very important. The objectives of this study were to evaluate the performance of the MicroScan system (Beckman Coulter, USA) with newly developed Korean Antimicrobial Susceptibility Testing Panels (KSCM panels) for antimicrobial susceptibility testing (AST) against clinical isolates in South Korea. METHODS: Three KSCM panels were designed in this study. For the performance evaluation, a total of 1,325 clinical isolates including 1,027 of Gram-negative bacilli and 298 Gram-positive cocci collected from eight general hospitals in South Korea were used. The results by KSCM panels were compared with those by conventional methods. RESULTS: By KSCM-1 panel for Gram-positive cocci, the rates of categorical agreement (CA) were >90% in all the antimicrobials tested in this study. The rates of major error (ME) were also 90%, ME rates <3%, and VME rates <1.5%. CONCLUSION: The newly developed three KSCM panels for MicroScan system (Beckman Coulter) showed excellent performance in AST against a large number of clinical isolates, and they are applicable to clinical microbiology laboratories.

Performance Evaluation of SENTiFIT 270 and FOB Gold Reagent for Detecting Fecal Occult Blood / 대한임상미생물학회지

BACKGROUND: Fecal occult blood tests have been widely used to screen for colorectal cancer. SENTiFIT 270 (Sentinel diagnostics, Italy) is a fecal occult blood test with an immunochemical method that utilizes FOB Gold reagents. We evaluated the performance of SENTiFIT 270 using the FOB Gold reagent. In addition, FOB Gold was evaluated with the HITACHI 7180 (Hitachi Ltd., Japan). METHODS: The precision and linearity of the SENTiFIT 270 was evaluated in accordance with applicable Clinical and Laboratory Standard Institute guidelines. The comparison study between SENTiFIT 270-FOB Gold and the OC-Sensor (Eiken chemical Co., Japan) was performed using stool specimens. RESULTS: In the precision evaluation, the total precision of SENTiFIT 270-FOB Gold was 4.94% and 2.54% at high and low concentrations, respectively. The HITACHI 7180-FOB Gold had excellent precision of 4.60% and 2.09% at high and low concentrations, respectively. Linearity was also excellent for the SENTiFIT 270-FOB Gold and HITACHI 7180-FOB Gold at 0.9987 and 0.9986, respectively. The SENTITIF 270-FOB Gold showed excellent agreement with a kappa value of 0.830 and a concordance rate of 93.6%. The HITACHI 7180-FOB Gold showed high agreement with a kappa value of 0.832 and a concordance rate of 93.9%. CONCLUSION: The SENTiFIT 270-FOB Gold showed excellent performance in accuracy, linearity, and comparative inspection ability.

Differences in Colistin-resistant Acinetobacter baumannii Clinical Isolates Between Patients With and Without Prior Colistin Treatment

BACKGROUND: The increasing morbidity and mortality rates associated with Acinetobacter baumannii are due to the emergence of drug resistance and the limited treatment options. We compared characteristics of colistin-resistant Acinetobacter baumannii (CR-AB) clinical isolates recovered from patients with and without prior colistin treatment. We assessed whether prior colistin treatment affects the resistance mechanism of CR-AB isolates, mortality rates, and clinical characteristics. Additionally, a proper method for identifying CR-AB was determined. METHODS: We collected 36 non-duplicate CR-AB clinical isolates resistant to colistin. Antimicrobial susceptibility testing, Sanger sequencing analysis, molecular typing, lipid A structure analysis, and in vitro synergy testing were performed. Eleven colistin-susceptible AB isolates were used as controls. RESULTS: Despite no differences in clinical characteristics between patients with and without prior colistin treatment, resistance-causing genetic mutations were more frequent in isolates from colistin-treated patients. Distinct mutations were overlooked via the Sanger sequencing method, perhaps because of a masking effect by the colistin-susceptible AB subpopulation of CR-AB isolates lacking genetic mutations. However, modified lipid A analysis revealed colistin resistance peaks, despite the population heterogeneity, and peak levels were significantly different between the groups. CONCLUSIONS: Although prior colistin use did not induce clinical or susceptibility differences, we demonstrated that identification of CR-AB by sequencing is insufficient. We propose that population heterogeneity has a masking effect, especially in colistin non-treated patients; therefore, accurate testing methods reflecting physiological alterations of the bacteria, such as phosphoethanolamine-modified lipid A identification by matrix-assisted laser desorption ionization-time of flight, should be employed.

Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System

BACKGROUND: National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. METHODS: Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. RESULTS: The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66–72% and 29–31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38–41%, 33–41%, and <0.1–2%, respectively, from 2013 to 2015. The carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. CONCLUSIONS: Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains.

Nationwide Survey of Blood Culture Protocol in Clinical Microbiology Laboratories in Korea / 대한임상미생물학회지

BACKGROUND: The recovery of bacteria from blood can be affected by many factors. Standardization of blood culture methods is important for reliability. Herein, we aimed to investigate blood culture protocols in Korea. METHODS: We performed a multicenter survey with a questionnaire about blood culture practices, which was sent by email to directors and clinical physicians in charge of clinical microbiology laboratories in May 2014. Total data from 18 participating hospitals were analyzed to be used as current baseline data, which is necessary to optimize blood culture protocols. RESULTS: Many laboratories included recommended blood volume, which is a major factor for bacteria recovery rate. This varied across participating laboratories. For adults, blood sampling of 10 mL was recommended by 10 laboratories and 20 mL was recommended by 5 laboratories. For children who weighed 14-36 kg and less than 14 kg, blood sampling of 10 mL (n=8) and 5 mL (n=7) was recommended, respectively. For neonates, less than 1 mL was recommended by 12 laboratories. CONCLUSION: Substantial variations in blood culture protocols were seen across participating clinical microbiology laboratories. Efforts to standardize this protocol should be undertaken.