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In this study, we describe an Enterobacter ludwigii clinical isolate that is resistant to both carbapenems and colistin in South Korea. Antimicrobial susceptibility testing revealed that E. ludwigii CRE2104-31 was non-susceptible to all tested antibiotics except fosfomycin. Whole genome sequencing identified a 323-kbp IncHI2 plasmid, pCRE2104-31a, that was co-harbouring mobile colistin resistance (mcr)-9.1 and blaIMP-1. In comparison with other full plasmids, pCRE2104-31a exhibited the closest similarity to a plasmid from the Klebsiella pneumoniae strain CNR48 from France, with 19.9% query coverage and 99% identity. Notably, we observed five tandem repeats of blaIMP-1 and aac(6′)-Il genes, accompanied by multiple attCs within a class I integron on the Tn402-like transposon. The unit of blaIMP-1-attC-aac(6′)-Il-attC might have accumulated due to multiple convergent events. In addition to mcr-9.1 and blaIMP-1, various other antibiotic resistance-associated genes were identified in the plasmid, as follows: blaTEM-1B, aph(3′)-I, aph(3′)-Ia, aac(6′)-Il, aac(6′)-IIc, aac(6′)-IIa, aph(6)-Id, aph(3′')-Ib, aadA2b, aac(6′)-Ib3, sul, dfrA19, qnrB2, aac(6′)-Ib-cr, ere(A), and qacE. A conjugation assay showed that the mcr-9.1/blaIMP-1-co-bearing plasmid was self-transmissible to E. coli J53. However, colistin and carbapenem resistance could not be transferred to E. coli due to high incompatibility. The convergence of mcr and carbapenemase genes is thought to be host-dependent among Enterobacteriaceae. The emergence of extensively drug-resistant E. ludwigii co-harbouring MCR-9.1 and a multicopy of blaIMP-1 would pose a significant threat within the compatible Enterobacteriaceae.

ABSTRACT With the introduction of ceftazidime-avibactam worldwide, the antimicrobial activity of new β-lactam/β-lactamase inhibitors (BL/BLIs) needs to be investigated. From January 2020 to June 2023, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were collected. With a broth microdilution test of new BL/BLIs, cross-activity test with nine combinations of BLs and new BLIs and dose-escalation titration test for non-susceptible isolates were conducted to investigate inhibitory activities of new BLIs. A total of 188 isolates was collected and most isolates (186/188, 98.9%) carried the KPC-2 gene exclusively, while two isolates (1.1%) co-harbored NDM-1. Among the 186 KPC-2-producing isolates, 184 (98.9%) were susceptible to ceftazidime-avibactam, 173 (93.0%) to imipenem-relebactam, and 184 (98.9%) to meropenem-vaborbactam. All isolates non-susceptible to imipenem-relebactam or meropenem-vaborbactam became susceptible when avibactam replaced relebactam or vaborbactam, with 7 of 11 (63.6%) imipenem-relebactam non-susceptible isolates and both (100.0%) of the meropenem-vaborbactam non-susceptible isolates. When the minimum inhibitory concentrations (MICs) of BLs were compared using log2 scales, combinations with avibactam showed statistically significant efficacy in lowering MICs compared to relebactam and vaborbactam (all P < 0.05). In the dose-escalation test of new BLIs, increasing dose of all new BLIs corresponded to increased susceptibility to BLs. Ceftazidime-avibactam exhibited excellent susceptibility against KPC-2-producing Enterobacterales unless co-harboring metallo-β-lactamase. The cross-combination test against non-susceptible isolates suggests that the inhibitory activity of avibactam was superior to those of relebactam or vaborbactam. Increasing the dose of new BLIs produced increased susceptibility to BLs, suggesting that high-concentration regimen need to be developed.IMPORTANCEThis study investigated 188 Klebsiella pneumoniae carbapenemase (KPC)-2-producing Enterobacterales collected from January 2020 to June 2023 in a tertiary care hospital of Korea. Most isolates were susceptible to ceftazidime-avibactam (98.9%) and meropenem-vaborbactam (98.9%), while susceptibility to imipenem-relebactam was lower (93.0%). The cross-combination test using nine combinations of the individual β-lactams (BLs) and new β-lactamase inhibitors (BLIs) showed that the inhibitory activity of avibactam was significantly superior to relebactam or vaborbactam when the Log2 MIC of BLs were compared for each combination with BLIs (all P < 0.05). The dose-escalation test of new BLIs demonstrated that increasing doses of new BLIs corresponded to increased susceptibility to BLs. Taken together, this study illustrates the excellent activity of ceftazidime-avibactam against KPC-2-producing Enterobacterales and suggests further investigation into high-concentration regimens for potentially non-susceptible clinical isolates.

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.

ABSTRACT In October 2022, we experienced a significant increase in samples showing high galactomannan (GM) indexes ranging from 6.22 to 10.58, as determined by the Platelia Aspergillus antigen immunoassay, also known as the GM test. After reviewing the medical records of nine GM antigenemia cases that did not show evidence of invasive aspergillosis, we found that these patients had received total parenteral nutrition (TPN) products from the same manufacturer, whose supplier of the glucose component had recently changed. The TPN products supplied by the specific manufacturer in October were subjected to a GM assay. The glucose component of the products from three different lot numbers exhibited strong positive results in the GM assay. Microbiological investigations through fungal culture and PCR on the TPN products were negative. The present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM test results. The source of GM in the glucose component was glucoamylase, which was produced from Aspergillus niger to obtain glucose monohydrate from starch. Investigation of three commercially available glucoamylase products exhibited positive GM and 1,3-β-D-glucan tests with various titers positive up to 1:1,000 dilutions, while fungal cultures were all negative. Quality assurance measures of TPN products to prevent GM contamination should be emphasized during the manufacturing process to avoid unnecessary additional diagnostic procedures and overtreatment of invasive aspergillosis due to false-positive GM tests. IMPORTANCE This manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.

Introduction: Poor liquefaction of pyogenic liver abscesses, which makes drainage impossible at the time of diagnosis, is not infrequent. The impact of poor liquefaction and subsequent drainage failure on clinical outcomes is unknown. Methods: We conducted a retrospective study with all patients diagnosed with liver abscesses from July 2017 through June 2020. Late drainage (LD) was defined as drainage performed ≥48 h after diagnosis due to poor liquefaction. Logistic regression was performed to identify the factors associated with late or non-drainage (LD/ND). The Cox proportional hazard model was used to identify the variables related to abscess recurrence by 90 days after diagnosis. Results: A total of 153 patients were included. Thirty (19.6%) patients underwent LD and 54 (35.3%) did not undergo drainage. Other than non-cystic appearance, LD/ND was associated with smaller size (adjusted odds ratio [aOR] 0.85, 95% confidence interval [CI] 0.73–0.98, p = 0.031) and culture-negativity (aOR 2.69, 95% CI 1.14–6.67, p = 0.027). Current hepatopancreaticobiliary malignancy was the only significant predictor of 90-day recurrence. Neither LD/ND (OR, 0.56; 95% CI, 0.13–2.41; p = 0.426) nor LD (OR, 1.26; 95% CI, 0.23–5.55; p = 0.719) was associated with recurrence by 90 days. The incidence of late complications was reduced by drainage, without a reduction in the duration of hospitalization. Conclusion: Several clinical features were associated with undrainable liver abscesses. Neither LD/ND nor ND had an adverse impact on clinical outcomes.

Since May 2022, monkeypox (MPX) cases have been reported from several European countries, and this outbreak rapidly spread globally. Although MPX is not a new disease, most clinicians in nonendemic countries are unfamiliar with it. In addition, this current outbreak, unlike previous outbreaks in Africa, shows unique features in terms of epidemiology, transmission routes, and clinical manifestation. Most cases were men who have sex with men, had no travel history to an MPX endemic area, and presented with anogenital lesions, suggesting human-to-human transmission via close contact during sexual activity. In the emergency department setting, rapid identification of suspected cases and implementation of effective infection control and preventive measures are critical for preventing further transmission to healthcare workers and other patients. Emergency department clinicians should be aware of the clinical presentations of MPX and be alert to patients presenting with fever and vesicular rash or sexually transmitted disease-associated rash, especially among those with travel history to countries reporting an MPX outbreak. This brief review provides current information of MPX to help emergency department clinicians understand the epidemiology, transmission, clinical manifestation, diagnosis, treatment, and infection prevention and control of MPX.

Objectives: Vancomycin and teicoplanin are glycopeptides with activity against Enterococcus faecium. However, studies on the clinical efficacy of teicoplanin are limited. This study aimed to compare the therapeutic efficacy of teicoplanin and vancomycin in E. faecium bacteremia. Methods: We identified patients with bloodstream infections prospectively from July 2015 to December 2016 in 14 hospitals as part of a multicenter nationwide surveillance. Patients with E. faecium monomicrobial bacteremia were selected. Teicoplanin and vancomycin groups included patients treated with either agent for ≥48 hours. The primary outcome was 30-day all-cause in-hospital mortality. The Cox proportional hazards model with inverse probability weighting was used to account for the imbalance in baseline characteristics between the two groups. Results: Among 97 patients with E. faecium bacteremia, 33 (34%) were treated with teicoplanin and 64 (66%) with vancomycin. There were no significant differences in 30-day in-hospital mortality (18.2% vs 26.6%, P = 0.358) and 7-day mortality (6.1% vs 15.6%, P = 0.212). Furthermore, multivariable analysis confirmed that the use of teicoplanin was not significantly associated with mortality (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.86; P = 0.494). Conclusion: We found no significant differences in the clinical outcomes. These findings suggest teicoplanin as a useful alternative to vancomycin.

Abstract Background We investigated the trend change in vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) prevalence among methicillin-resistant S. aureus (MRSA) bacteremia strains and antistaphylococcal antibiotic use together with mutation studies of vancomycin resistance-related gene loci to evaluate the impact of changes in antibiotic use after new antistaphylococcal antibiotics became available. Methods Among 850 healthcare-associated MRSA isolates from 2006 to 2019 at a tertiary hospital in South Korea, hVISA/VISA was determined by modified PAP/AUC analysis, and the identified hVISA/VISA strains were genotyped. Gene mutations at vraSR, graSR, walKR, and rpoB were studied by full-length sequencing. Antistaphylococcal antibiotic use in 2005–2018 was analyzed. Results Two VISA and 23 hVISA strains were identified. The prevalence rate ratio of hVISA/VISA carrying mutations at the two-component regulatory systems among MRSA was 0.668 (95% CI 0.531–0.841; P = 0.001), and the prevalence rate ratio of hVISA/VISA carrying rpoB gene mutations was 1.293 (95% CI 0.981–1.702; 174 P = 0.068). Annual vancomycin use density analyzed by days of therapy (DOT) per 1,000 patient-days did not decrease significantly, however the annual average length of time analyzed by the number of days vancomycin was administered for each case showed a significantly decreasing trend. Conclusions During the 14-year period when the average length of vancomycin therapy decreased every year with the availability of alternative antibiotics, the prevalence of hVISA/VISA did not decrease significantly. This seems to be because the resistant strains carrying the rpoB mutations increased despite the decrease in the strains carrying the mutations at the two-component regulatory systems.

Abstract Purpose To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. Methods We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration–time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. Results A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539–0.886; AUC for Ctrough, 0.760; 95% CI 0.627–0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 μg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60–86.62; p = 0.010). Conclusion Mean Ctrough ≥ 13.94 μg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

IntroductionThe effect of tixagevimab/cilgavimab (Evusheld™; AstraZeneca, UK) should be evaluated in the context of concurrent outbreak situations.MethodsFor serologic investigation of tixagevimab/cilgavimab during the BA.5 outbreak period, sera of immunocompromised (IC) hosts sampled before and one month after tixagevimab/cilgavimab administration and those of healthcare workers (HCWs) sampled one month after a 3rd shot of COVID-19 vaccines, five months after BA.1/BA.2 breakthrough infection (BI), and one month after BA.5 BI were investigated. Semi-quantitative anti-spike protein antibody (Sab) test and plaque reduction neutralizing test (PRNT) against BA.5 were performed.ResultsA total of 19 IC hosts (five received tixagevimab/cilgavimab 300 mg and 14 received 600 mg) and 41 HCWs (21 experienced BA.1/BA.2 BI and 20 experienced BA.5 BI) were evaluated. Baseline characteristics did not differ significantly between IC hosts and HCWs except for age and hypertension. Sab significantly increased after tixagevimab/cilgavimab administration (median 130.2 BAU/mL before tixagevimab/cilgavimab, 5,665.8 BAU/mL after 300 mg, and 10,217 BAU/mL after 600 mg; both P < 0.001). Sab of one month after the 3rd shot (12,144.2 BAU/mL) or five months after BA.1/BA.2 BI (10,455.8 BAU/mL) were comparable with that of tixagevimab/cilgavimab 600 mg, while Sab of one month after BA.5 BI were significantly higher (22,216.0 BAU/mL; P < 0.001). BA.5 PRNT ND50 significantly increased after tixagevimab/cilgavimab administration (median ND50 29.6 before tixagevimab/cilgavimab, 170.8 after 300 mg, and 298.5 after 600 mg; both P < 0.001). The ND50 after tixagevimab/cilgavimab 600 mg was comparable to those of five months after BA.1 BI (ND50 200.9) while ND50 of one month after the 3rd shot was significantly lower (ND50 107.6; P = 0.019). The ND50 of one month after BA.5 BI (ND50 1,272.5) was highest among tested groups, but statistical difference was not noticed with tixagevimab/cilgavimab 600 mg.ConclusionTixagevimab/cilgavimab provided a comparable neutralizing activity against the BA.5 with a healthy adult population who were vaccinated with a 3rd shot and experienced BA.1/BA.2 BI.

Objectives This study introduced a novel Automatic Needle Destroyer (AND) to an emergency department (ED) and assessed its effect on healthcare providers’ work. Methods Between August and September 2019, in the ED of a tertiary hospital in Seoul, we conducted a mixed-methods study to evaluate the efficiency, safety, and usability of the AND using video analysis, surveys, and in-depth interviews, wherein participants described the advantages and disadvantages of the AND. Results Compared to the existing method, introducing the AND significantly reduced the operating time from 2.32 ± 1.14 seconds to 1.77 ± 3.71 seconds (p < 0.001). The normal operation rate was 90.6%. The rate of needle-stick injuries (NSIs) and the mean system usability scale (SUS) showed no significant differences. The in-depth interviews indicated that the disadvantages of the AND were mostly operational. The advantages were related to profit, reduced direct contact with hazardous waste, and behavioral changes, such as not having to recap syringes. Conclusions We introduced the AND to an ED environment, where NSIs occur frequently and many syringes are used, to evaluate its effect on providers’ work. The AND reduced the time for needle disposal, but the normal operation rate was low. No significant differences were found in the SUS score or the rate of NSIs. Although there are some restrictions on introducing the AND immediately, this study’s results showed its potential usefulness. Efforts to improve the operation of the device and a longer study period are needed to fully achieve safety and efficiency.

Objectives: We implemented a stratified risk analysis to predict the development of active tuberculosis (TB) in liver transplantation (LT) recipients based on IGRA and chest images in a TB-endemic area. Methods: In this retrospective cohort study, LT recipients who tested for IGRA between May 2008 and December 2017 were included. Chest images compatible with old TB lesions were considered as positive images. LT recipients were divided into six groups: LT recipients with history of treated TB, image (+)/IGRA (+), image (+)/IGRA (-), image (-)/IGRA (+), image (-)/IGRA (-) and LTBI treated. The Cox regression model was used to analyze risk groups. Results: Among the 717 eligible LT recipients included in this study, 21 patients developed active TB. Incidence rates of TB were 2,261, 724, and 119 cases/100,000 person-years in the 1st, 2nd, and ≥ 3rd year after transplantation, respectively. History of treated TB (HR 18.92; 95% CI 4.10–87.25) and image (+)/IGRA (+) (HR 10.86; 95% CI 2.75–42.89) were independent risk factors for developing active TB. IGRA (+) with a negative image was not a risk factor. Conclusions: Our findings suggested that both IGRA and chest images should be considered to identify risk groups for LTBI treatment.

In an investigation of six anti-SARS-CoV-2 antibody kits with different target antigen and methodology, each kit showed comparable performance. As false-positive reactions occurred independently with different kits, specificity increased to 100% when pairs of kits were used. With three-kit combination, both sensitivity (99.1%) and specificity (100%) increased.

BackgroundThe impact of nirmatrelvir/ritonavir treatment on shedding of viable virus in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear.MethodsA prospective cohort study evaluating mildly ill COVID-19 patients was conducted. Virologic responses were compared between nirmatrelvir/ritonavir-treatment and supportive care groups. Risk factors and relevant clinical factors for shedding of viable virus were investigated.ResultsA total of 80 COVID-19 patients were enrolled and 222 sputum specimens were collected. Ten patients were dropped during follow-up, and 33 patients in the nirmatrelvir/ritonavir and 37 in the supportive care groups were compared. The median age was 67 years, and 67% were male. Clinical characteristics were similar between groups. Viral loads decreased significantly faster in the nirmatrelvir/ritonavir group compared with the supportive care group (P < 0.001), and the slope was significantly steeper (–2.99 ± 1.54 vs. –1.44 ± 1.52; P < 0.001). The duration of viable virus shedding was not statistically different between groups. In the multivariable analyses evaluating all collected specimens, male gender (OR 2.51, 95% CI 1.25–5.03, P = 0.010), symptom score (OR 1.41, 95% CI 1.07–1.87, P = 0.015), days from symptom onset (OR 0.72, 95% CI 0.59–0.88, P = 0.002), complete vaccination (OR 0.09, 95% CI 0.01–0.87, P = 0.038), and BA.2 subtype (OR 0.49, 95% CI 0.26–0.91, P = 0.025) were independently associated with viable viral shedding, while nirmatrelvir/ritonavir treatment was not.ConclusionNirmatrelvir/ritonavir treatment effectively reduced viral loads of SARS-CoV-2 Omicron variants but did not decrease the duration of viable virus shedding.

Abstract Background Sequence type (ST) 17 vancomycin-resistant Enterococcus faecium (VREF) is frequently isolated in nosocomial settings. The aim of this study was to identify whether ST17 contributes to subsequent bacteremia more often than other STs among hospitalized patients carrying VREF. Methods A retrospective cohort study was conducted in patients carrying ST17 VREF and those with non-ST17 VREF. Rectal screening according to hospital policy was used to identify patients with VREF. Subsequent VREF bacteremia events within a year of detection of colonization were recorded. Cox regression analysis was used to adjust the covariates involved in determining the association between ST17 and subsequent bacteremia events. Results The cohorts comprised 52 patients with ST17 and 169 patients with non-ST17 VREF. One-year VREF bacteremia-free rates were 85.9% and 90.2%, respectively. In multivariate analysis, ST17 was associated with subsequent bacteremia at an adjusted hazard risk (aHR) of 4.02 (95% confidence interval [CI], 1.32–12.29). Liver transplantation (aHR, 40.08; 95% CI, 4.87–329.76) and hematologic malignancy (aHR, 20.97; 95% CI, 4.87–87.82) were also significant. All cases of subsequent bacteremia in ST17 VREF carriers were caused by ST17; however, subsequent bacteremia in non-ST17 carriers was often caused by ST17 or another ST variant. Conclusions A specific genotype, ST17 is a predictor of subsequent bacteremia in hospitalized patients carrying VREF. Patients with a hematologic malignancy and those receiving a liver transplant are also at high risk. More targeted strategies may be needed to prevent VREF infection in hospitals.

Background: Treatment of device-related infections by drug-resistant Staphylococcus aureus can be challenging, and combination therapy has been proposed as a potential solution. We compared the effectiveness of levofloxacin–rifampin and ciprofloxacin–rifampin combinations in killing methicillin-resistant S. aureus (MRSA) using a time–kill assay. Methods: We randomly selected 15 vancomycin-susceptible S. aureus (VSSA) strains, 3 vancomycin-intermediate S. aureus (VISA) strains, and 12 heterogeneous VISA (hVISA) strains from the Asian Bacterial Bank. Time–kill experiments were performed in duplicate for each isolate. Viable bacterial counts were determined at 0 h, 4 h, 8 h, and 24 h for the ciprofloxacin– and levofloxacin–rifampin combinations at 1× MIC and 0.5× MIC. We compared synergistic and antagonistic interactions between the two combinations. Results: The viable bacterial count significantly decreased after 24 h of exposure to ciprofloxacin–rifampin and levofloxacin–rifampin combinations, with synergy observed more frequently in isolates exposed to ciprofloxacin–rifampin (43.3%) than levofloxacin–rifampin (20.0%) (p = 0.0082). The synergistic interactions of both combinations were more frequently observed in resistant strains with high MICs of ciprofloxacin (≥16 mg/L) and levofloxacin (≥8 mg/L). Levofloxacin tended to exhibit more frequent antagonistic interactions with rifampin than ciprofloxacin, although there was no statistical difference in antagonism between the two combinations. Conclusions: Our study demonstrated that ciprofloxacin exhibits superior synergistic activity against MRSA strains, including VISA/hVISA, when combined with rifampin compared with levofloxacin. High MICs of fluoroquinolones were found to predict synergism. Our results suggest that ciprofloxacin may be a more effective choice than levofloxacin for combination therapy with rifampin in the treatment of MRSA infections.

Clinical applicability of rapid diagnostic test kit for SARS-CoV-2 antibodies was evaluated. The kit detected antibodies from day 9–56 of illness. IgG bands were observed up to 1: 1000 dilutions. The kit could detect 90.5% of IgG and 61.9% of IgM antibodies of mild febrile patients without pneumonia.

For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50 ≥ 20 was comparable among the four immunoassays (Cohen’s kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson’s R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.

The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.

The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20–71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0–18.0) compared to those in the ChAd group (median 23.0, IQR 8.0–43.0, P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0–9.0, P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL, P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL, P=0.002) and BNT (1.656 ± 1.925 IU/mL, P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.

Abstract Background Although β-lactam monotherapy may be sufficient in non-critically ill patients with community-acquired pneumonia, the value of combination antibiotic regimens in community-onset neutropenic pneumonia remains unclear. Methods A retrospective cohort study was conducted to compare the effects of combination antibiotic regimens to those of β-lactam monotherapy in cancer patients with community-onset neutropenic pneumonia. Electronic medical records of patients diagnosed with community-onset neutropenic pneumonia between March 1995 and February 2015 at a tertiary care center were reviewed. Results During the study period, 165 cancer patients with community-onset neutropenic pneumonia were identified. Seventy-two patients received β-lactam monotherapy and 93 received combination therapy (β-lactam plus either a macrolide or fluoroquinolone). Causative pathogens were identified in 27.9% of the patients, and only two were positive for atypical pathogens. Although 30-day mortality was higher in the β-lactam group (15.3% versus 4.3%; P = 0.015), combination therapy was not associated with a statistically significant survival benefit in the multivariate analysis (hazard ratio 0.85, 95% confidence interval 0.20–3.67; P = 0.827). Duration of neutropenia, C-reactive protein level, and Multinational Association for Supportive Care in Cancer risk index were significant factors for 30-day mortality. In a subgroup analysis of patients treated with cefepime, the most frequently used β-lactam (63.0%), combination therapy also showed no significant survival benefit. Conclusions Combination antibiotic regimens were not associated with a survival benefit over β-lactam monotherapy in the treatment of community-onset neutropenic pneumonia. Unnecessary combination therapy should be reconsidered in cancer patients who are at high risk for adverse drug reactions and colonization with multi-drug resistant organisms.

Background Although the study of respiratory microbiota has been an active field of research, obtaining the appropriate respiratory samples for healthy controls remains to be a challenge. As such, this study aims to evaluate the use of endotracheal tube washing as a viable control for sputum samples. Methods A total of 14 subjects, including 8 healthy respiratory controls and 6 diabetic patients without any respiratory disease, were enrolled in this study, during which the endotracheal tubes used in their scheduled routine surgery were collected. Pre-operative oral gargles were also collected from non-diabetic subjects. Results 16S amplicon sequencing revealed similar taxa composition in endotracheal tube washings and oral gargles in the healthy control subjects, although the relative abundance of 11 genus level operational taxonomic units was significantly different between the two sample sources. The diabetic subjects showed relatively lower diversity than those of non-diabetic subjects. The proportion range of the most abundant taxa detected in each endotracheal tube washings were 10.1–33.2%. Conclusion Endotracheal tube washing fluid may provide healthy control samples for upper respiratory investigations without incurring any additional risk to the subject.

Purpose Tuberculosis (TB) is one of the most important diseases that cause significant mortality and morbidity in young children. Data on TB transmission from an infected child are limited. Herein, we report a case of disseminated TB in a child and conducted a contact investigation among exposed individuals. Methods A 4-year-old child without Bacille Calmette-Guérin vaccination was diagnosed as having culture-proven disseminated TB. The child initially presented with symptoms of inflammatory bowel disease, and nosocomial and kindergarten exposures were reported. The exposed individuals to the index case were divided into 3 groups, namely household, nosocomial, or kindergarten contacts. Evaluation was performed following the Korean guidelines for TB. Kindergarten contacts were further divided into close or casual contacts. Chest radiography and tuberculin skin test or interferon-gamma-releasing assay were performed for the contacts. Results We examined 327 individuals (3 household, 10 nosocomial, and 314 kindergarten contacts), of whom 18 (5.5%), the brother of the index patient, and 17 kindergarten children were diagnosed as having latent TB infection (LTBI). LTBI diagnosis was more frequent in the children who had close kindergarten contact with the index case (17.1% vs. 4.4%, P=0.007). None of the cases had active TB. Conclusion This is the first reported case of TB transmission among young children from a pediatric patient with disseminated TB in Korea. TB should be emphasized as a possible cause of chronic diarrhea and failure to thrive in children. A national TB control policy has been actively applied to identify Korean children with LTBI.

Staphylococcal scarlet fever (SSF) is characterized by an exanthem without enanthem, bullae, or exfoliation, and is known to be related to Staphylococcus aureus toxins, especially superantigens. It has been reported in children and young adults. Herein, we report the first case of an elderly patient with SSF caused by staphylococcal enterotoxin M (SEM), associated with otitis externa. The patient presented with maculopapular rashes on both arms, thighs, and abdomen and with erythroderma on the face, ears, neck, chest, and back, all of which was followed by desquamation on the face, ears, and trunk. A culture of ear discharge grew methicillin susceptible S. aureus that was only positive for SEM among the superantigens tested. Keywords: Staphylococcal scarlet fever, Staphylococcal enterotoxin M, Staphylococcal enterotoxin-like toxin M

Introduction: During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia. Methods: The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4 μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia. Results: Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (

Abstract Background Carriage of methicillin-resistant Staphylococcus aureus (MRSA) is an important risk factor of subsequent infection. The purpose of our study was to compare the rates of subsequent infection among newly-admitted patients carrying MRSA between community-genotype and hospital-genotypes Methods In this retrospective cohort study, we compared the rates of subsequent MRSA infection, time to subsequent infection and mortality in the following 6 months between the community-genotype ST72 MRSA cohort and the hospital-genotypes ST5 / ST239 MRSA cohort. Results We identified 198 patients carrying ST72 and 156 patients carrying ST5 or ST239. There was no difference in the rates of subsequent infection between ST72 cohort and ST5 / ST239 cohort (13.1% vs. 12.8%; P = 0.931). The median time to development of subsequent infection was not significantly different (27 days vs. 88 days; P = 0.0877). The Kaplan-Meier method showed no difference in the cumulative rate of being free of subsequent infection between the cohorts (P = 0.9209). Overall mortality rates at 6 months did not differ (1.5% vs. 1.9%; P = 1.000) Conclusions We found no evidence that rates of subsequent MRSA infection were different between newly-admitted patients carrying community-genotype ST72 MRSA and those whom carrying hospital-genotypes ST5 or ST239 MRSA.

In 2018, the Clinical and Laboratory Standards Institute (CLSI) revised ciprofloxacin (CIP)-susceptible breakpoint for Enterobacteriaceae from ≤1 μg/mL to ≤0.25 μg/mL, based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. However, clinical data supporting the lowered CIP breakpoint are insufficient. This retrospective cohort study evaluated the clinical outcomes of patients with bacteremic urinary tract infections (UTIs) caused by Enterobacteriaceae, which were previously CIP-susceptible and changed to non-susceptible. Bacteremic UTIs caused by Enterobacteriaceae with CIP minimal inhibitory concentration (MIC) ≤ 1 μg/mL were screened, and then patients treated with CIP as a definitive treatment were finally included. Patients in CIP-non-susceptible group (MIC = 0.5 or 1 μg/mL) were compared with patients in CIP-susceptible group (MIC ≤ 0.25 μg/mL). Primary endpoints were recurrence of UTIs within 4 weeks and 90 days. A total of 334 patients were evaluated, including 282 of CIP-susceptible and 52 of CIP-non-susceptible. There were no significant differences in clinical outcomes between two groups. In multivariate analysis, CIP non-susceptibility was not associated with recurrence of UTIs. CIP non-susceptibility based on a revised CIP breakpoint, which was formerly susceptible, was not associated with poor clinical outcomes in bacteremic UTI patients were treated with CIP, similar to those of the susceptible group. Further evaluation is needed to guide the selection of definitive antibiotics for UTIs.

In a uniformly convex and q-uniformly smooth Banach space with q ∈ ( 1 , 2 ] , one use VIP to indicate a variational inclusion problem involving two accretive mappings and CFPP to denote the common fixed-point problem of an infinite family of strict pseudocontractions of order q. In this paper, we introduce a composite extragradient implicit method for solving a general symmetric system of variational inclusions (GSVI) with certain VI and CFPP. We then investigate its convergence analysis under some weak conditions. Finally, we consider the celebrated LASSO problem in Hilbert spaces.

Background/AimsMetformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer.MethodsAmong 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed.ResultsThe incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007).ConclusionsMetformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.

To better understand extensively drug resistant Streptococcus pneumoniae, we assessed clinical and microbiological characteristics of 5 extensively drug-resistant pneumococcal isolates. We concluded that long-term care facility residents who had undergone tracheostomy might be reservoirs of these pneumococci; 13- and 23-valent pneumococcal vaccines should be considered for high-risk persons; and antimicrobial drugs should be used judiciously.

We present two algorithms for finding a zero of the sum of two monotone operators and a fixed point of a nonexpansive operator in Hilbert spaces. We show that these two algorithms converge strongly to the minimum norm common element of the zero of the sum of two monotone operators and the fixed point of a nonexpansive operator.

The proximal split feasibility problem has been studied. A regularized method has been presented for solving the proximal split feasibility problem. Strong convergence theorem is given.

We study the convergence of implicit Picard iterative sequences for strongly accretive and strongly pseudocontractive mappings. We have also improved the results of Ćirić et al. (2009).

An equilibrium problem and a strictly pseudocontractive nonself-mapping are investigated. Strong convergence theorems of common elements are established based on hybrid projection algorithms in the framework of real Hilbert spaces.

The aim of this paper is to study the solvability of a third-order nonlinear neutral delay differential equation of the form {α(t)[β(t)(x(t)+p(t)x(t−τ))′]′}′+f(t,x(σ1(t)),x(σ2(t)),…,x(σn(t)))=0, t≥t0. By using the Krasnoselskii's fixed point theorem and the Schauder's fixed point theorem, we demonstrate the existence of uncountably many bounded nonoscillatory solutions for the above differential equation. Several nontrivial examples are given to illustrate our results.

A new nonlinear mapping is introduced. Hybrid projection algorithms are considered for the class of new nonlinear mappings. Strong convergence theorems are established in a real Banach space.

We introduce an iterative method for a pair of hemirelatively nonexpansive mappings. Strong convergence of the purposed iterative method is obtained in a Banach space.

We consider a modified Halpern type iterative algorithm for a family of quasi-ϕ-nonexpansive mappings in the framework of Banach spaces. Strong convergence theorems of the purposed iterative algorithms are established.

A one-step iteration with errors is considered for a family of asymptotically nonexpansive nonself mappings. Weak convergence of the purposed iteration is obtained in a Banach space.

A new nonlinear mapping is introduced. The convergence of Ishikawa iterative processes for the class of asymptotically pseudocontractive mappings in the intermediate sense is studied. Weak convergence theorems are established. A strong convergence theorem is also established without any compact assumption by considering the so-called hybrid projection methods.

The purpose of this paper is to consider the weak convergence of an iterative sequence for finding a common element in the set of solutions of generalized equilibrium problems, in the set of solutions of classical variational inequalities, and in the set of fixed points of nonexpansive mappings.

We consider viscosity approximation methods with demi-continuous strong pseudo-contractions for a non-expansive semigroup. Strong convergence theorems of the purposed iterative process are established in the framework of Hilbert spaces.

The purpose of this work is to introduce an iterative method for finding a common element of a solution set of a generalized equilibrium problem, of a solution set solutions of a variational inequality problem and of a fixed point set of a strict pseudocontraction. Strong convergence theorems are established in the framework of Hilbert spaces.

The article "Investigation of Correlation between HDL and Mean Platelet Volume in Patients Having Small Dense LDL Values" explores the relationship between high-density lipoprotein (HDL) and mean platelet volume (MPV) in patients with small dense low-density lipoprotein (sdLDL) values. The study found a statistically significant negative correlation between HDL and MPV, suggesting that higher HDL levels may lead to lower platelet size and activity. The research highlights the potential role of HDL in modulating platelet function and its impact on thrombotic events. The study was conducted at Kyung Hee University Hospital in Seoul, South Korea, and was supported by Bom Medical. [Extracted from the article]