BACKGROUND:Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly.METHODS:To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020.RESULTS:In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively.CONCLUSION:The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Objectives: It is unclear whether the poor outcome of patients with severe vancomycin-resistant enterococci (VRE) infection is attributable to vancomycin resistance or to Enterococcus faecium (Efm), which predominates among VRE.Methods: Retrospective study of a prospectively identified cohort from nationwide surveillance. A cohort of consecutive, nonduplicate episodes of monomicrobial bloodstream infections (BSIs) caused by Efm in 2016 was selected. The primary outcome was all-cause, 30-day, in-hospital mortality. Inverse probability weighting was applied using the propensity score for vancomycin-resistant Efm (VREfm) BSI. Results: A total of 241 Efm BSI episodes were included, of which 59 (24.5%) were VREfm. Patients with VREfm BSI were younger but had similar comorbidities to those with vancomycin-sensitive Efm (VSEfm) BSI. Multivariable logistic regression revealed that younger age, previous piperacillin-tazobactam use, and steroid use were significant risk factors for VREfm BSI, but 30-day in-hospital mortality did not differ significantly between groups (35.6% and 23.6% for VREfm and VSEfm, respectively; odds ratio, 1.79; 95% confidence interval, 0.95-3.37; P = 0.101). However, Cox regression with inverse probability weighting revealed that vancomycin resistance was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.18; 95% confidence interval, 1.03-4.62; P = 0.041).Conclusion: In patients with Efm BSI, vancomycin resistance was independently associated with mortality.& COPY; 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Background. Clinically relevant categorization of antimicrobial resistance is critical to mitigating the threat it poses. Difficult-to-treat resistance (DTR) is a recently proposed category defined as nonsusceptibility to all first-line antibiotic agents. Methods. A retrospective study was conducted with nonduplicate cases of gram-negative bloodstream infection (GNBSI) caused by 4 major taxa (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter species) identified from a nationwide surveillance database. DTR was defined as nonsusceptibility to all the beta-lactams and fluoroquinolones tested. Patient characteristics and mortality were compared between DTR GNBSI and GNBSI caused by carbapenem-resistant but not DTR and extended-spectrum cephalosporin-resistant but not DTR isolates using Centers for Disease Control and Prevention definitions. Adjusted odds ratios (aORs) for 30-day in-hospital mortality were examined for DTR in overall and in propensity score-matched cohorts. Results. A total of 1167 episodes of monomicrobial GNBSI were identified, and 147 (12.6%) of the isolates were DTR. The majority of DTR isolates were Acinetobacter species (79.6%) and P. aeruginosa (17.7%). DTR infections were associated with previous antibiotic use, healthcare contact, ventilator use, and lower respiratory tract infection. Crude mortality for GNBSI caused by DTR was 50.3%. A multivariable model showed that only DTR, but not other categories, was significantly associated with mortality (adjusted odds ratio [aOR], 3.58 [95% confidence interval {CI}, 1.27-10.19]). DTR was also a significant predictor for mortality in the analysis of propensity score-matched cohorts (aOR, 3.48 [95% CI, 1.82-6.79]). Conclusions. In patients with GNBSI, DTR was associated with higher mortality than those in other resistance categories. Our findings suggest that DTR could be useful for surveillance and prognostication.

Abstract Background Infections caused by multidrug-resistant (MDR) organisms are associated with poorer clinical outcomes and higher economic burden. However, there has been limited data on the impact of MDR infection on the performance status of patients. Methods Patients with bloodstream infections by S. aureus, E. faecium, E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii have been identified prospectively as a part of a multicenter nationwide surveillance for antimicrobial resistance. Medical records of the patients enrolled from July 2015 through December 2016 were reviewed for demographic, clinical, microbiologic characteristics, and patient outcome. MDR was defined as MRSA, VRE, and nonsusceptibility to one or more agents in three or more different classes of antibiotics for Gram-negative bacteria. Performance status was evaluated by Eastern Cooperative Oncology Group (ECOG) Performance Status before admission and at discharge. Primary outcome was any decline in ECOG at discharge. Multiple logistic regression was used to identify independent risk factors for ECOG decline. Results A total of 19 hospitals participated to the network. The numbers of subjects were 410 for S. aureus, 392 for E. faecium, 708 for E. coli and K. pneumoniae, and 678 for P. aeruginosa and A. baumannii. In univariate analysis, bacteremia by MDR organisms was associated with ECOG decline only in patients with P. aeruginosa (18.4% vs. 10.3%, OR 1.962, 95% CI 1.132–3.399) and A. baumannii (27.6% vs. 11.8%, OR 2.834, 95% CI 1.328–6.045) infections. Patients with MDR K. pneumoniae infection had lower risk of ECOG decline (6.6% vs. 15.8%, OR 0.378, 95% CI 0.183–0.780). Multivariable analysis also showed that infection by MDR organism was independently associated with ECOG decline in patients with P. aeruginosa or A. baumannii infections (OR 2.068, 95% CI 1.478–2.895), but not with other MDR organisms. Comorbidities and initial ECOG showed higher effect size in patients with S. aureus and E. faecium infections. Conclusion In this large multicenter nationwide study, bloodstream infections caused by MDR P. aeruginosa and A. baumannii were associated with higher risk of decline in performance status at discharge. MDR status did not show association in infections by other species. Disclosures All authors: No reported disclosures.

Information on the most current status of antimicrobial resistance (AMR) in local and national levels has critical importance. However, collection and analysis of a large number of antimicrobial susceptibility test (AST) results often results in additional workload in healthcare facilities and latency in final reporting. We sought to develop an automated nationwide surveillance network in Korea. Data collection servers were set up at each participating institutions, which collects AST results of every bacterial isolate from blood, cerebrospinal fluids, urine, and respiratory specimens. Collected results are anonymized and transmitted to central data server every day without human input. End-user can perform various analyses using data warehouse server through web interface. Only first isolates of same species from individual patients were included in analysis. A total of 19 hospitals located in various regions in Korea participated to the network. From January 2015 through December 2017, AST results of 347,356 isolates were collected. The proportion of MRSA among S. aureus (n = 17,761) was 65.3%, which declined gradually from 71.5 to 62.3% during study period (P < 0.001). The proportion of VRE increased from 29.3 to 36.3% (P = 0.001). Resistance rates of E. coli (n = 63,628) to third and fourth generation cephalosporins, fluoroquinolone, and piperacillin–tazobactam were 31.6, 23.0, 44.0, and 4.2%, respectively. Resistance rates of K. pneumoniae (n = 16,875) to same classes were 32.2, 28.1, 31.0 and 19.1%, respectively. Among E. coli and K. pneumoniae, 0.4 and 4.3% were resistant to carbapenem. Resistance rates of P. aeruginosa (n = 12,895) to carbapenem was 30.5%. However, 72.7% of A. baumannii isolates (n = 9,885) were resistant to carbapenem. Colistin resistance rate was still low at 0.5%. We have established a fully automated nationwide surveillance network for AMR in Korea. Our system provided data on the most current status of AMR, which revealed increase in resistance rates among major Gram-negative pathogens compared with previous studies. Schematic diagram of the Korean Antimicrobial Resistance Surveillance Network (KARSNet). Temporal trends of the resistance rates of S. aureus and E. faecium. Temporal trends of the resistance rates of major Gram-negative species. All authors: No reported disclosures.

To evaluate the impacts of fluconazole minimum inhibitory concentration (MIC) according to primary antifungal agents on Candida glabrata bloodstream infection (BSI), a multicenter retrospective cohort study was conducted in Korea, concerning the time period from January 2010 to February 2016. A total of 197 adult patients with C. glabrata BSI were included in the study, and neutropenia (P = 0.026), APACHE II score (P = 0.004), and fluconazole resistance (HR 3.960, 95% CI 1.395-11.246, P = 0.010) were associated with 30-day mortality in multivariate analysis. In subgroup analysis, fluconazole MIC = 32 μg/mL in the azole-treated group (HR 6.691, 95% CI 1.569-28.542, P = 0.010) and fluconazole MIC ≥ 64 μg/mL in the non-azole-treated group (HR 3.337, 95% CI 1.183-9.411, P = 0.023) showed the highest hazard ratio (HR) for 30-day mortality. Increased fluconazole MIC was associated with poor outcome both in azole- and non-azole-treated patients with C. glabrata BSI.

While carbapenems are the drug of choice to treat extended-spectrum-β-lactamase (ESBL)-producing strains, some alternative carbapenem-sparing regimens are suggested for antibiotic stewardship. We experienced a case of ciprofloxacin treatment failure for acute pyelonephritis caused by an apparently susceptible Escherichia coli. A 71-year-old woman presented the emergency department with fever for 7 days and bilateral flank pain for 2 days. The laboratory results and abdominopelvic computed tomography finding were compatible with acute pyelonephritis. During 3-day ciprofloxacin therapy, the patient remained febrile with persistent bacteremia. After the change in antibiotics to ertapenem, the patient’s clinical course started to improve. ESBL-producing E. coli isolates were identified in all three consecutive blood samples. Pulsed-field gel electrophoresis (PFGE) patterns, serotypes, and sequence types showed the three isolates were derived from the identical strain. The isolates produced CTX-M-14 type ESBL belonging to the ST69 clonal group. Despite in vitro susceptibility, the failure was attributed to a gyrA point mutation encoding Ser83Leu within quinolone resistance-determining regions. This case suggests that ciprofloxacin should be used cautiously in the treatment of serious infections caused by ciprofloxacin-susceptible, ESBL-producing E. coli, even in acute pyelonephritis because in-vitro susceptibility tests could fail to detect certain genetic mutations.

Stenotrophomonas maltophilia (SM) has emerged as an important nosocomial pathogen with high morbidity and mortality. Because of its unique antimicrobial susceptibility pattern, appropriate antimicrobial therapy for SM bacteremia is still challenging, especially in immunocompromised patients. The present study was performed to assess clinical predictors of SM bacteremia in adult patients with hematologic malignancy. From 2006 through 2016, a case-control study was performed at a tertiary-care hospital. Case patients were defined as SM bacteremia in patients with hematologic malignancy. Date- and location-matched controls were selected from among patients with gram-negative bacteremia (GNB) other than SM. A total of 118 cases of SM bacteremia were identified and compared to 118 controls. While pneumonia was the most common source of SM bacteremia, centralline-associated infection was most common in the controls. The overall 30-day mortality rate of cases with SM bacteremia was significantly higher than that of the controls (61.0 and 32.2%, respectively; P < 0.001). A multivariable analysis showed that polymicrobial infection, previous SM isolation, the number of antibiotics previously used ≥ 3, and breakthrough bacteremia during carbapenem therapy were significantly associated with SM bacteremia (all P < 0.01). Previous use of trimethoprim/sulfamethoxazole (TMP/SMX) was negatively association with SM bacteremia (P = 0.002). Our data suggest that SM is becoming a significant pathogen in patients with hematologic malignancy. Several clinical predictors of SM bacteremia can be used for appropriate antimicrobial therapy in hematologic patients with suspected GNB.

Background: Fluoroquinolones are antibiotics commonly used in the treatment of infections caused by Streptococcus pneumoniae. However, rates of fluoroquinolone resistance are increasing with their frequent use. We designed this study to verify current fluoroquinolone resistance rates and risk factors for community-onset pneumococcal pneumonia. Methods: A retrospective case-control study was conducted in a tertiary referral hospital. The study population comprised patients admitted for pneumococcal pneumonia between January 2011 and May 2017. The case group included community-onset pneumonia caused by levofloxacin-nonsusceptible S. pneumoniae. The control group consisted of two patients with levofloxacin-susceptible S. pneumoniae who were admitted around the same time as each case. Results: A total of 198 pneumococcal pneumonia cases were identified during the study period. Twenty-five levofloxacin-resistant S. pneumoniae cases and 3 levofloxacin-intermediate S. pneumoniae cases were included in the case group (nonsusceptibility rate=14.1%). Multivariate analysis showed that healthcare-associated factors (odds ratio [OR] 4.78, 95% confidence interval [CI] 1.39-16.43, p=0.013), bronchopulmonary disease (OR 3.79, 95% CI 1.07-13.40, p=0.039), cerebrovascular disease (OR 6.08, 95% CI 1.24-29.75, p=0.026), and exposure to fluoroquinolones within the previous 3 months (OR 5.89, 95% CI 1.21-28.68, p=0.028) were associated with nonsusceptibility to levofloxacin. Conclusion: Independent risk factors for levofloxacin-nonsusceptible pneumococcal pneumonia were recent hospitalization, bronchopulmonary disease, cerebrovascular disease, and prior antibiotic use within 3 months. Careful selection of empirical antibiotics is thus needed in at-risk patients. Similarly, efforts to prevent the interpersonal spread of drug-resistant pathogens in long-term care facilities and to restrict unnecessary fluoroquinolone prescriptions are important.

To evaluate the effects of demographic and perceptive factors on the knowledge, perception, and behavior regarding antibiotic use in the general public, we conducted three serial telephone interview surveys in 2010, 2012, and 2015. Computer-aided telephone interview was conducted, with a predetermined quota stratified by sex, age, and geographic location. Respondents who answered correctly to four or more questions were categorized as having better knowledge. A total of 3013 respondents participated. Better knowledge was associated with age < 60 years (OR 1.37, 95% CI 1.04–1.82), college education (OR 1.57, 95% CI 1.26–1.97), healthcare-related occupation or education (OR 2.26, 95% CI 1.52–3.36), and media exposure (OR 1.25, 95% CI 1.02–1.54). In contrast, correct antibiotic use behavior was associated with male sex (OR 1.48, 95% CI 1.27–1.73), older age (OR 1.63, 95% CI 1.34–1.99), and being married (OR 1.26, 95% CI 1.04–1.52), along with better knowledge (OR 1.43, 95% CI 1.19–1.71). However, multifaceted analysis indicated that better knowledge was associated with correct behavior in all subgroups. Other demographic factors were associated only in respondents with poor knowledge. Various factors other than knowledge on antibiotics, many of them traditionally underappreciated, affect antibiotic use behavior.

To evaluate effect of empirical combination of a β-lactam to vancomycin and vancomycin monotherapy in Staphylococcus aureus bacteremia (MSSA-B), we conducted a retrospective cohort study. Electronic medical records of individuals who were diagnosed with MSSA-B between January 2005 and February 2015 at a tertiary care center were reviewed. Patients were classified into three groups according to empirical antibiotic regimen (BL group, β-lactam; VAN group, vancomycin; BV group, combination of β-lactam and vancomycin), and 30-day all-cause mortality of each group was compared. During the study period, 561 patients with MSSA-B were identified. After exclusion of 198 patients (36 with poly-microbial infection, 114 expired within 2 days, and 48 already received parenteral antibiotics) and a matching process, 46 patients for each group were included. Baseline characteristics were similar except for severity and comorbidity scores. The 30-day mortality for all three groups were not significantly different (BL 4.3%, VAN 6.5%, BV 8.7%; P = 0.909). In a multivariate analysis, type of empirical antibiotic regimen was not statistically associated with 30-day all-cause mortality. In comparison with the VAN group, the BV group yielded a HR of 0.579 (95% CI = 0.086–3.890, P = 0.574). Pitt bacteremia score was the only significant factor for mortality. The empirical combination of a β-lactam to vancomycin was not associated with lower mortality in treating MSSA-B, compared to vancomycin monotherapy.

We evaluated serologic response of 42 Middle East respiratory syndrome coronavirus (MERS-CoV)-infected patients according to 4 severity groups: asymptomatic infection (Group 0), symptomatic infection without pneumonia (Group 1), pneumonia without respiratory failure (Group 2), and pneumonia progressing to respiratory failure (Group 3). None of the Group 0 patients showed seroconversion, while the seroconversion rate gradually increased with increasing disease severity (0.0%, 60.0%, 93.8%, and 100% in Group 0, 1, 2, 3, respectively; P = 0.001). Group 3 patients showed delayed increment of antibody titers during the fourth week, while Group 2 patients showed robust increment of antibody titer during the third week. Among patients having pneumonia, 75% of deceased patients did not show seroconversion by the third week, while 100% of the survived patients were seroconverted (P = 0.003).

During the 2015 Korean MERS outbreak, we experienced atypical presentations of MERS-CoV infections in three immunocompromised hosts that warranted exceptional management. Case 1 showed delayed symptom development after a four-day asymptomatic period, Case 2 experienced a 20-day incubation period, and Case 3 exhibited persistent viral shedding without clinical deterioration. Recognizing these exceptions is extremely important in the management of MERS-CoV-exposed or -infected patients and for control of potential MERS outbreaks.

We investigated the molecular epidemiology and microbiological characteristics of 51 Escherichia coli isolates causing hospital-acquired pneumonia (HAP) in eight Asian areas. Sequence type 131 (ST131) was the most prevalent among E. coli isolates causing HAP, especially in South Korea, Thailand, and the Philippines. The current study showed that CTX-M-15-producing E. coli ST131 has emerged in and disseminated among patients with HAP in Asia. Our data suggest that this pandemic clone poses an important public health threat even in nosocomial infections.

Hee Jae Huh, M.D., Jae-Hoon Ko, M.D., Young-Eun Kim, M.D., Chang-Hun Park, M.D., Geehay Hong, M.D., Rihwa Choi, M.D., Shinae Yu, M.D., Sun Young Cho, M.D., Ji-Man Kang, M.D., Myoung-Keun Lee, M.T., Chang-Seok Ki, M.D., Eun-Suk Kang, M.D., Nam Yong Lee, M.D., Jong-Won Kim, M.D., Yae-Jean Kim, M.D., Young Eun Ha, M.D., Cheol-In Kang, M.D., Doo Ryeon Chung, M.D., Kyong Ran Peck, M.D., and Jae-Hoon Song, M.D.. Ann Lab Med 2017;37:81-3. https://doi.org/10.3343/alm.2017.37.1.81

Background: The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. Methods: Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient’s serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. Results: Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. Conclusions: For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.

BACKGROUND:As community-genotype methicillin-resistant Staphylococcus aureus (MRSA) strains spread into hospitals, the genotypes of the MRSA strains causing hospital-acquired (HA) infections have become more diverse. We describe clinical characteristics of nosocomial MRSA infections by a community-genotype of sequence type (ST) 72.MATERIALS AND METHODS:A case-control study was designed among patients with HA-MRSA infections. Forty patients with infections caused by ST72-MRSA SCCmec type IV were selected as cases. Cases were matched to the controls with 106 patients infected with ST5/ST239 MRSA, which are representative hospital genotypes in Korea.RESULTS:Patients infected with ST72 isolates were younger than those with ST5/ST239 isolates. Female gender predominated among ST72 MRSA group compared to ST5/ST239 MRSA group. Solid tumor was a more frequent underlying disease in MRSA infections by ST72 isolates, whereas underlying renal, lung, heart, and neurologic diseases were more frequently found in those by ST5/ST239 isolates. The most common type of infection was pneumonia in both ST72 and ST5/ST239 groups (45.0% vs. 51.9%), followed by skin and soft tissue infection (SSTI). Female gender and underlying solid tumor were identified to be independent predictors for MRSA infections by ST72 isolates. All-cause mortality rates (20.0% vs. 30.2%) were not different between the groups.CONCLUSION:A community-genotype MRSA, ST72 isolate has emerged as a nosocomial pathogen presenting as hospital-acquired pneumonia and SSTI. Although differences in underlying disorders were found, the distribution of infection type and mortality rate did not differ between the groups.

Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.

Because we experienced gentamicin failure in Klebsiella pneumoniae bacteraemia that was susceptible to gentamicin despite amikacin resistance, as determined by VITEK 2, we evaluated the true susceptibility and mechanism of resistance. We screened 2818 K. pneumoniae isolates during a 1-year period at a university hospital and reviewed anti-microbial susceptibility reports using the VITEK 2 system. The minimum inhibitory concentration was substantiated by broth microdilution (BMD), and the presence of 16S rRNA methylase genes and aminoglycoside-modifying enzymes was also investigated. A total of 131 amikacin-resistant isolates from 19 patients were gentamicin non-resistant according to the VITEK 2 system. Among these, we were able to collect isolates from 12 patients (63.2 %), and a single isolate from each patient was tested. Eleven of the gentamicin non-resistant isolates (91.7 %) showed high-level resistance to both amikacin and gentamicin by BMD in association with the armA gene. Gentamicin is not an adequate treatment option for amikacinresistant K. pneumoniae, even if VITEK 2 reports susceptibility.