Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development

Background@#In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. @*Methods@#The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. @*Results@#An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3–4 months. @*Conclusion@#We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media.Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Change in Severity and Clinical Manifestation of MIS-C Over SARSCoV-2 Variant Outbreaks in Korea

Background@#There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. @*Methods@#We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020–May 2021; delta period as June 2021–December 2021; and omicron period as January 2022–April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. @*Results@#A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1–83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2–2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. @*Conclusion@#Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Predicting Phenotypic Antimicrobial Resistance in Escherichia coli Isolates, Using Whole Genome Sequencing Data / 대한임상미생물학회지

Background@#The application of genotypic antimicrobial sensitivity tests (ASTs) is dependent on the reliability of the predictions of phenotypic resistance. In this study, routine AST results and the presence of corresponding antimicrobial resistance genes were compared. @*Methods@#Eighty-four extended-spectrum-β-lactamase-producing Escherichia coli isolates from poultry-related samples were included in the study. The disk diffusion method was used to test for susceptibility to antimicrobial compounds, except colistin susceptibility, which was tested using the agar dilution method. Whole-genome sequencing (WGS) was performed using a NextSeq 550 instrument (Illumina, USA). Antimicrobial resistance genes were detected using ResFinder 4.1. @*Results@#Concordance rates between the genotype and phenotype ranged from 35.7% (ciprofloxacin) to 96.4% (tetracycline). The presence of tet was a good predictor of phenotypic resistance. @*Conclusion@#The genotype was a good predictor of tetracycline phenotypic resistance, but there was a gap in the prediction of phenotypic ASTs for trimethoprim-sulfamethoxazole, chloramphenicol, gentamicin, and ciprofloxacin. We concluded that WGS-based genotypic ASTs are inadequate to replace routine phenotypic ASTs.

Clinical Usefulness of the QMAC-dRAST System for AmpC β-lactamase-Producing Enterobacterales / 대한임상미생물학회지

Background@#Rapid antimicrobial susceptibility testing (RAST) is important for the appropriate treatment of bloodstream infections. The QMAC-dRAST system (QuantaMatrix Inc., Korea) can directly perform RAST using positive blood culture samples with microscopic imaging. This study aimed to evaluate the performance of the QMAC-dRAST system for AmpCβ-lactamase-producing Enterobacterales. @*Methods@#Eighty isolates (20 Morganella morganii, 20 Serratia marcescens, 10 Klebsiella aerogenes, 10 Enterobacter cloacae, and 20 Citrobacter freundii) and 14 antimicrobial agents were included in the antimicrobial susceptibility testing (AST). The performance of the QMAC-dRAST system was evaluated by simulating the clinical blood culturing process. We conducted a comparative evaluation of the QMAC-dRAST and Vitek 2 systems (bioMérieux Inc., France). Broth microdilution tests were performed as the reference method to resolve any discrepancies in the AST results between the two systems. @*Results@#For 20 M. morganii and 20 S. marcescens, the categorical agreement (CA) between the QMAC-dRAST and Vitek 2 systems increased from 55.4% to 83.8% after AST algorithm optimization. Moreover, the discrepancy rates decreased as follows: from 19.1% to 5.4% very major errors (VME), from 38.3% to 4.3% major errors (ME), and from 14.6% to 12.1% minor errors (mE) for the QMAC-dRAST system compared to the Vitek 2 system. For all 80 tested isolates, the QMAC-dRAST system showed 93.0% CA, 1.7% VME, 2.3% ME, and 4.9% mE. @*Conclusion@#The QMAC-dRAST system was comparable to the Vitek 2 system after AST algorithm optimization for AmpC β-lactamase-producers, which are major pathogens and require time to express the enzyme. However, further modifications of the AST algorithm are still warranted.

Core Elements for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals

Currently, antimicrobial resistance (AMR) is a major threat to global public health. The antimicrobial stewardship program (ASP) has been proposed as an important approach to overcome this crisis. ASP supports the optimal use of antimicrobials, including appropriate dosing decisions, administration duration, and administration routes. In Korea, efforts are being made to overcome AMR using ASPs as a national policy. The current study aimed to develop core elements of ASP that could be introduced in domestic medical facilities. A Delphi survey was conducted twice to select the core elements through expert consensus.The core elements for implementing the ASP included (1) leadership commitment, (2) operating system, (3) action, (4) tracking, (5) reporting, and (6) education. To ensure these core elements are present at medical facilities, multiple departments must collaborate as teams for ASP operations. Establishing a reimbursement system and a workforce for ASPs are prerequisites for implementing ASPs. To ensure that ASP core elements are actively implemented in medical facilities, it is necessary to provide financial support for ASPs in medical facilities, nurture the healthcare workforce in performing ASPs, apply the core elements to healthcare accreditation, and provide incentives to medical facilities by quality evaluation criteria.

Trends in Isolation and Antimicrobial Susceptibility of Enteropathogenic Bacteria in 2011-2019 at a Korean Tertiary Care Hospital Compared with Data in the Preceding Reports / 대한임상미생물학회지

Background@#Environmental sanitation plays a significant role on the prevalence of enteropathogenic bacteria. This study aimed to determine the trends in the prevalence and antimicrobial resistance profiles of enteropathogenic bacteria from 2011 to 2019. @*Methods@#A retrospective analysis was performed using data from stool cultures of Salmonella spp., Shigella spp., Plesiomonas shigelloides , Yersinia spp., Vibrio spp., and Campylobacter spp. Samples were obtained between 2011 and 2019 from Severance Hospital. Antimicrobial susceptibility profile was determined using the disk diffusion method for nontyphoidal Salmonella (NTS) and Campylobacterspp., following the Clinical and Laboratory Standards Institute (CLSI) guidelines. @*Results@#The number of specimens obtained for stool culture increased significantly from 13,412 during the period of 1969–1978, to 48,476 over the past nine years (2011–2019), whereas the ratio of positive specimens decreased significantly from 1,732 (12.9%) to 449 (0.9%). The proportion of samples positive for Salmonella Typhi decreased from 472 (93.6%, 1969–1978) to 4 (1.5%, 2011–2019), whereas the proportion of NTS increased from 14 (2.8%, 1969–1978) to 261 (96.7%, 2011–2019). Among all the enteropathogenic bacteria isolated, Shigella spp. accounted for 60.0% (1,039) isolates from 1969 to 1978, but only 1.6% (7) from 2011 to 2019. Campylobacter was the second most prevalent enteropathogenic bacteria, accounting for 29.4% isolates (132). Among the NTS strains isolated from 2016 to 2019, their susceptibility rates to ampicillin and sulfamethoxazole-trimethoprim were 51.1% and 85.2%, respectively. Additionally, the susceptibility rate of Campylobacter to ciprofloxacin was 15.8%. @*Conclusion@#The prevalence of Salmonella Typhi and Shigella spp. significantly decreased, whereas those of NTS and Campylobacter spp. increased. Therefore, continuous monitoring of ciprofloxacin-resistant Campylobacter spp. is of vital importance.

Usefulness of delta neutrophil index to predict neurologic outcome in patients with aneurysmal subarachnoid hemorrhage

Objective@#Aneurysmal subarachnoid hemorrhage (SAH) is a common emergency condition, resulting in high morbidity and mortality. The delta neutrophil index (DNI), which reflects the fraction of circulating immature granulocytes, is significantly associated with systemic inflammation after infection or sterile injury. Aneurysmal SAH also leads to systemic inflammation after a brain injury. This study aimed to evaluate the relationship between the DNI and poor neurologic outcomes in patients with aneurysmal SAH. @*Methods@#We retrospectively identified patients (>18 years old) with aneurysmal SAH consecutively admitted to the emergency department (ED) between January 1, 2011, and November 30, 2018. The diagnosis of aneurysmal SAH was confirmed using clinical and radiological findings. DNI was determined at 0, 24, 48, and 72 hours after ED admission. The primary result was a poor neurologic outcome using the modified Rankin scale. @*Results@#A total of 352 patients with aneurysmal SAH were included in this study. A multivariable logistic regression model revealed that a high value of DNI at 24 hours after ED admission was a strong independent predictor of poor neurologic outcome upon discharge (odds ratio [OR], 1.471; 95% confidence interval [CI], 1.081-2.001; P=0.014). Among patients with aneurysmal SAH, DNI >1.0% at 24 hours was significantly associated with poor neurologic outcomes upon discharge (OR, 5.037; 95% CI, 3.153-8.044; P<0.001). @*Conclusion@#DNI can be determined easily and rapidly after ED admission without any additional cost or time burden. A high DNI value at 24 hours after ED admission is significantly associated with a poor neurologic outcome upon discharge among patients with aneurysmal SAH.

First Report of Roseomonas aerofrigidensis Isolated from the Peritoneal Fluid of a Gastric Cancer Patient / 대한임상미생물학회지

Roseomonas aerofrigidensis is a gram-negative, strictly aerobic, non-motile bacterium, which was first isolated in 2017 in South Korea. We present the first report of the isolation of R.aerofrigidensis from the peritoneal fluid of a 38-year-old woman with a history of metastatic gastric cancer with peritoneal carcinomatosis. The isolate was resistant to cotrimoxazole. Further research on clinical and microbiological responses to several antibiotics are warranted.

Usefulness of delta neutrophil index to predict neurologic outcome in patients with aneurysmal subarachnoid hemorrhage

Objective@#Aneurysmal subarachnoid hemorrhage (SAH) is a common emergency condition, resulting in high morbidity and mortality. The delta neutrophil index (DNI), which reflects the fraction of circulating immature granulocytes, is significantly associated with systemic inflammation after infection or sterile injury. Aneurysmal SAH also leads to systemic inflammation after a brain injury. This study aimed to evaluate the relationship between the DNI and poor neurologic outcomes in patients with aneurysmal SAH. @*Methods@#We retrospectively identified patients (>18 years old) with aneurysmal SAH consecutively admitted to the emergency department (ED) between January 1, 2011, and November 30, 2018. The diagnosis of aneurysmal SAH was confirmed using clinical and radiological findings. DNI was determined at 0, 24, 48, and 72 hours after ED admission. The primary result was a poor neurologic outcome using the modified Rankin scale. @*Results@#A total of 352 patients with aneurysmal SAH were included in this study. A multivariable logistic regression model revealed that a high value of DNI at 24 hours after ED admission was a strong independent predictor of poor neurologic outcome upon discharge (odds ratio [OR], 1.471; 95% confidence interval [CI], 1.081-2.001; P=0.014). Among patients with aneurysmal SAH, DNI >1.0% at 24 hours was significantly associated with poor neurologic outcomes upon discharge (OR, 5.037; 95% CI, 3.153-8.044; P<0.001). @*Conclusion@#DNI can be determined easily and rapidly after ED admission without any additional cost or time burden. A high DNI value at 24 hours after ED admission is significantly associated with a poor neurologic outcome upon discharge among patients with aneurysmal SAH.

Prevalence and Molecular Epidemiology of ExtendedSpectrum-β-Lactamase (ESBL)-Producing Escherichia coli From Multiple Sectors of the Swine Industry in Korea: A Korean Nationwide Monitoring Program for a One Health Approach to Combat Antimicrobial Resistance

Background@#One health is a flexible concept with many facets, including the environment, community, and the nosocomial super-bacteria resistance network. We investigated the molecular prevalence of extended-spectrum-β-lactamase-producing Escherichia coli (ESBL-EC) in workers, livestock, and the farm environment in Korea. @*Methods@#ESBL-EC isolates were obtained from samples from 19 swine farms, 35 retail stores, seven slaughterhouses, and 45 related workers throughout Korea from August 2017 to July 2018, using ChromID ESBL (BioMérieux, Marcy l’Etoile, France) agar and enrichment broth. The presence of ESBL and mobilized colistin resistance (mcr) genes and antimicrobial resistance were determined. Clonality was evaluated with pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). @*Results@#In total, 232 ESBL-EC isolates were obtained from 1,614 non-duplicated samples (14.4% positive rate). The ESBL-EC isolates showed regional and source-related differences. blaCTX-M-55 (N = 100), blaCTX-M-14 (N = 65), blaCTX-M-15 (N = 33), and blaCTX-M-65 (N = 23) were common ESBL types. The ESBL-EC isolates showed high resistance rates for various antimicrobial classes; however, all isolates were susceptible to carbapenem. One swine-originating colistin-resistant isolate did not carry any known mcr gene. PFGE was successful for 197 of the 232 isolates, and most PFGE types were heterogeneous, except for some dominant PFGE types (O, R, T, U, and V). MLST of 88 isolates was performed for representative PFGE types; however, no dominant sequence type was observed. @*Conclusions@#The proportion of ESBL-EC in swine industry-related samples was significant, and the isolates harbored common clinical ESBL gene types. These molecular epidemiologic data could provide important evidence for antimicrobial-resistance control through a one health approach.

Surveillance of Coronavirus Disease 2019 (COVID-19) Testing in Clinical Laboratories in Korea

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, an online laboratory surveillance system was established to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-PCR (rRT-PCR) testing capacities and results. SARS-CoV-2 rRT-PCR testing data were collected from 97 clinical laboratories, including 84 medical institutions and 13 independent clinical laboratories in Korea. We assessed the testing capacities to utilize SARS-CoV-2 rRT-PCR based on surveillance data obtained from February 7th to June 4th, 2020 and evaluated positive result characteristics according to the reagents used and sample types. A total of 1,890,319 SARS-CoV-2 rRT-PCR testing were performed, 2.3% of which were positive. Strong correlations were observed between the envelope (E ) gene and RNA-dependent RNA polymerase (RdRp )ucleocapsid (N ) genes threshold cycle (Ct) values for each reagent. No statistically significant differences in gene Ct values were observed between the paired upper and lower respiratory tract samples, except in the N gene for nasopharyngeal swab and sputum samples. Our study showed that clinical laboratories in Korea have rapidly expanded their testing capacities in response to the COVID-19 outbreak, with a peak daily capacity of 34,193 tests. Rapid expansion in testing capacity is a critical component of the national response to the ongoing pandemic.

First Report of Roseomonas aerofrigidensis Isolated from the Peritoneal Fluid of a Gastric Cancer Patient / 대한임상미생물학회지

Roseomonas aerofrigidensis is a gram-negative, strictly aerobic, non-motile bacterium, which was first isolated in 2017 in South Korea. We present the first report of the isolation of R.aerofrigidensis from the peritoneal fluid of a 38-year-old woman with a history of metastatic gastric cancer with peritoneal carcinomatosis. The isolate was resistant to cotrimoxazole. Further research on clinical and microbiological responses to several antibiotics are warranted.

Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea

The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with >9,000 confirmed cases as of March 25, 2020. COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world. Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea. These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety.

Performance of Modified-EUCAST Rapid Direct Antimicrobial Susceptibility Testing on Clinical Urine Samples / 대한임상미생물학회지

Background@#The rapid antimicrobial susceptibility testing (AST) performed on urine samples would guide the adequate choice of antibiotics for obtaining better treatment outcomes in patients. Our study aimed to evaluate the performance of the modified-EUCAST (European Committee on Antimicrobial Susceptibility Testing) rapid direct AST on urine samples. @*Methods@#From >2,000 urine samples, a total of 128 urine samples containing bacterial counts of ≥2 × 10 4 CFU/mL with a uniform bacterial shape were initially included based on flow cytometry (Sysmex UF-1000i, Japan) and Gram staining, respectively. A total of 103 samples showing the presence of Enterobacteriaceae were finally selected in this study. The urine samples were directly inoculated on Mueller-Hinton agar, which was used in the current EUCAST rapid direct AST on blood samples. The size of the growth inhibition zones around antimicrobial disks was measured using a digital scanner (BIOMIC vision analyzer, Giles scientific, USA) and further confirmed by visualization with naked eyes after incubation for 4, 6, and 8 hours. The AST interpretations were compared to those of the conventional VITEK 2 AST system (bioMérieux, France) and the discrepancies between both tests were confirmed with the E-test. @*Results@#The antibiotics, namely ampicillin, cefazolin, aztreonam, ceftazidime, cefotaxime, cefoxitin, cefepime, gentamicin, ciprofloxacin, and cotrimoxazole showed excellent correlations with modified-EUCAST rapid direct test and conventional ASTs with >0.75 weighted kappa values. The categorical agreement of the rapid direct AST was 1,442 (93.3%), with 76 (4.9%) minor error, 9 (0.6%) major error and 18 (1.2%) very major error, implicating the reliability of this method for clinical application. @*Conclusion@#Performing the modified-EUCAST rapid direct AST on urine samples can predict reliable AST results within 8 hours. The rapid direct AST can help the physicians to initiate adequate antimicrobial treatment for urinary tract infections.

The First Case of Ochrobactrum pseudogrignonense Bacteremia in Korea

No abstract available.

Isolation of Non-Hydrogen Sulfide-Producing Salmonella enterica Serovar Infantis from a Clinical Sample: the First Case in Korea

No abstract available.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.

Whole-Genome Analysis of bla(CTX-M-55)-Carrying Escherichia coli Among Pigs, Farm Environment, and Farm Workers

No abstract available.

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.