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OBJECTIVES This study compared the current smoking prevalence among adults with human immunodeficiency virus (HIV) infection to that of the general Korean population and analyzed changes in smoking prevalence and cessation rates from 2009 to 2020. METHODS The study included a total of 10,980 adults with HIV infection who underwent a health screening examination (National Health Insurance Service-National Health Information Database; NHIS-NHID), 1,230 individuals with HIV infection who participated in the Korea HIV/AIDS Cohort (KoCosHIV), and 76,783 participants from the Korea National Health and Nutrition Examination Survey (KNHANES). We estimated the current smoking prevalence and the quit ratio, defined as the ratio of former smokers to ever-smokers. RESULTS In the NHIS-NHID and KoCosHIV studies, the prevalence of current and former smoking among adults with HIV was 44.2% (95% confidence interval [CI], 43.2 to 45.1) and 15.6% (95% CI, 14.9 to 16.3), and 47.7% (95% CI, 43.7 to 51.8) and 16.9% (95% CI, 11.8 to 22.0), respectively. In the KNHANES, these rates were 22.5% and 18.1%, respectively. The standardized prevalence ratio of current smoking among adults with HIV was 1.76 in the NHIS-NHID and 1.97 in the KoCosHIV. Furthermore, the likelihood of quitting smoking was lower among adults with HIV than in the general population (NHIS-NHID: 26.1%; 95% CI, 25.0 to 27.1; KoCosHIV: 26.2%; 95% CI, 20.2 to 32.1; KNHANES: 44.6%; 95% CI, 44.5 to 44.6). Among HIV-positive adults, there was a 1.53% decline in the current smoking rate and a 2.86% increase in the quit ratio. CONCLUSIONS Adults with HIV were more likely to smoke and less likely to quit smoking than the general adult population. Tobacco screening and cessation strategies should specifically target this population.

Non-tuberculous mycobacteria (NTM) rarely manifest with lymphoma-like symptoms in immunocompetent adults. We report the case of a 70-year-old male with a disseminated Mycobacterium kansasii infection. Computed tomography revealed the presence of multiple lymph nodes in various areas. Biopsies confirmed the NTM infection. Urine and pus cultures confirmed M. kansasii. Empirical antibiotic treatment was initiated; however, the patient developed acute cholangitis. Despite interventions, including choledocholithotomy and broad-spectrum antibiotics, the patient succumbed to septic shock. This case underscores the necessity of maintaining suspicion and comprehensive testing for NTM infections to enable early diagnosis, appropriate treatment, and prevent fatal complications.

Background/Purpose: To investigate the virulence profiles and identify clinical and microbiological predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (A. baumannii) bacteremia. Methods: This retrospective cohort study enrolled adult patients with carbapenem-resistant A. baumannii (CRAB). Multivariate logistic regression was used to identify the predictors of 30-day mortality. All isolates were subjected to real-time polymerase chain reaction for virulence factors and genotyped using multilocus sequence typing. Results: Among the 153 patients with CRAB bacteremia, 66 % received appropriate definitive antibiotic therapy. The in-hospital and 30-day mortality rates were 58.3 and 23.5 %, respectively. Ultimately, we enrolled 125 patients with CRAB bacteremia in the analysis, excluding early mortality cases. All CRAB isolates carried blaOXA-23 and blaOXA-51. The clinical strains belonged to 10 sequence types (STs), and the major genotypes were ST191, ST195, ST451, and ST784. The distribution of virulence factors included surface adhesion (Ata, 84.8 %; ChoP, 7.2 %), biofilm formation (OmpA, 76.8 %), killing of host cells (AbeD, 99.2 %), toxins (LipA, 99.2 %), and conjugation (BfmR, 90.4 %). In multivariate logistic regression analysis, hemodialysis due to acute kidney injury and moderate to severe thrombocytopenia were significant risk factors associated with 30-day mortality. However, microbiological factors were not significant predictors. Conclusions: Clinical factors such as hemodialysis due to acute renal injury and moderate to severe thrombocytopenia have a greater influence on mortality in CRAB bacteremia compared with microbiological factors.

Background/Aims The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. Results A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85–1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77–1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59–0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. Conclusions In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.

Abstract This study aimed to characterize the molecular features and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Clinical CRAB isolates were obtained from blood cultures of adult patients with CRAB bacteremia, collected between July 2015 and July 2021 at a Korean hospital. Real-time polymerase chain reaction was used to detect 13 virulence genes, genotyping was conducted via multilocus sequence typing (MLST), and a Tenebrio molitor infection model was selected for survival analysis. Herein, 170 patients, from whom CRAB isolates were collected, showed the in-hospital mortality rate of 57.6%. All 170 clinical CRAB isolates harbored bla OXA-23 and bla OXA-51. MLST genotyping identified 11 CRAB sequence types (STs), of which ST191 was predominant (25.7%). Virulence genes were distributed as follows: basD, 58.9%; espA, 15.9%; bap, 92.4%; and ompA, 77.1%. In the T. molitor model, ST195 showed a significantly higher mortality rate (73.3% vs. 66.7%, p = 0.015) than the other groups. Our findings provide insights into the microbiological features of CRAB blood isolates associated with high mortality. We suggest a potential framework for using a T. molitor infection model to characterize CRAB virulence. Further research is warranted to elucidate the mechanisms by which virulence improves clinical outcomes.

This study evaluated the efficacy and safety of neutralizing monoclonal antibodies (mAbs) with usual care in patients with coronavirus disease 2019 (COVID-19). Randomized controlled trials comparing the efficacy and safety of neutralizing mAb treatment in patients with COVID-19 were identified using electronic database searches through March 10, 2023. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 13 trials (23 articles) involving 25,646 patients were included in this systematic review. Compared with usual care, neutralizing mAbs were associated with significantly reduced all-cause mortality in outpatients with COVID-19 (pooled risk ratios [RR], 0.41; 95% confidence interval (CI), 0.20–0.83; 12 studies), but not in inpatients. In the subgroup analysis, only outpatients infected prior to the emergence of Delta variant or those with mAb–VOC match had significantly reduced mortality, while no significant benefit was observed in patients infected with Delta and post–Delta variants or mAb–VOC mismatch. Moreover, the rate of hospitalization and number of hospital visits had significantly reduced only in outpatients infected prior to the emergence of the Delta variant and those with mAb–VOC match. Our systematic review used majority of the high-certainty evidence. Our study found neutralizing mAbs were beneficial for outpatients infected prior to Delta variant or mAb–VOC match. In the face of the continuous emergence of new COVID-19 variants, additional clinical data are needed to determine whether neutralizing mAb treatment will be effective for the newly emerging variants.

Background/Aims This study aimed to investigate the clinical characteristics and outcomes of fluorescent antinuclear antibody (FANA)-positive patients admitted for coronavirus disease 2019 (COVID-19) and identify FANA as a prognostic factor of mortality. Methods This retrospective study was conducted at a university-affiliated hospital with 1,048 beds from September 2020 to March 2022. The participants were consecutive patients who required oxygenation through a high-flow nasal cannula, non-invasive or mechanical ventilation, or extracorporeal membrane oxygenation, and conducted the FANA test within 48 hours of admission. Results A total of 132 patients with severe COVID-19 were included in this study, of which 77 (58.3%) had FANA-positive findings (≥ 1:80). FANA-positive patients were older and had higher inflammatory markers and 28-day mortality than FANA-negative patients. In the multivariate Cox proportional hazard regression analysis, FANA-positive findings (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.04–6.74), age (per 1-year; HR, 1.05; 95% CI, 1.01–1.10), underlying pulmonary disease (HR, 3.16; 95% CI, 0.97–10.26), underlying hypertension (HR, 2.97; 95% CI, 1.28–6.87), and blood urea nitrogen > 20 mg/dL (HR, 3.72; 95% CI, 1.09–12.64) were independent predictors of 28-day mortality. Remdesivir (HR, 0.34; 95% CI, 0.15–0.74) was found to be an independent predictor that reduced mortality. Conclusions Our findings revealed an autoimmune phenomenon in patients with severe COVID-19, which provides an ancillary rationale for strategies to optimize immunosuppressive therapy. In particular, this study suggests the potential of FANA to predict the outcomes of COVID-19.

Abstract Background This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. Methods This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. Results Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. Conclusion This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82–0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71–0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81–0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70–0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71–0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89–1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events.Trial registration: PROSPERO: registration number CRD42021294120.

Background: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. Methods: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. Results: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. Conclusions: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

Abstract We investigated the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. The in vitro activity of six two-drug combinations against CRAB isolates collected from the blood samples of patients with bloodstream infection was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, and 2 × minimum inhibitory concentration (MIC)] to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates. The effects of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam combinations were investigated. All 10 CRAB isolates in our study produced the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinases. The colistin-ceftolozane/tazobactam combination showed synergistic effects in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method. It also showed bactericidal effects in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there was substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assays (with a concordance of 31.7%). Our study demonstrated that two-drug combinations of colistin and ceftolozane/tazobactam could be useful treatment alternatives for CRAB infections. The effects of these antibiotic combinations should be evaluated using in vivo experimental models.

BackgroundThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the persistence of the pandemic, even with mass coronavirus disease 2019 (COVID-19) vaccination, have raised questions about the durability of immunity and extent of cross-reactive immunity after vaccination. This study aimed to characterize the humoral and cellular immune response to the mRNA-1273 vaccine using a prospective longitudinal cohort.MethodsWe recruited 177 young SARS-CoV-2 infection-naive adults. Two doses of mRNA-1273 vaccine were administered at 28-day intervals, and blood samples were collected at five time points: pre-vaccination (T0), 4 weeks after the first (T1) and second dose (T2), and 3 months (T3) and 6 months (T4) after the first dose. Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody, neutralizing antibody, and T-cell immune responses were evaluated.ResultsThe two-dose mRNA-1273 vaccination induced robust anti-SARS-CoV-2 antibody responses, which remained higher than the titers at T1 until T4. A higher peak anti-S antibody titer at T2 was associated with better cross-reactive immunity against Delta and Omicron variants and long-lasting (anti-S IgG and neutralizing antibody) humoral immunity up to T4. The overall T-cell immune response was not correlated with peak antibody titers (T-lymphocyte subpopulation analysis was not performed).ConclusionThis study showed that an early strong antibody response is predictive of longer humoral immunity and better cross-reactive neutralizing immunity against Delta and Omicron variants.

Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.

Abstract Background Critically ill patients in intensive care units (ICUs) often acquire opportunistic infections or are colonized by vancomycin-resistant enterococci (VRE), which limits therapeutic options and results in high case-fatality rates. In clinical practice, the beneficial effects of universal chlorhexidine gluconate (CHG) bathing on the control of VRE remain unclear. This study aimed to investigate whether 2% CHG daily bathing reduced the acquisition of VRE in the setting of a medical ICU (MICU) with VRE endemicity. Methods This quasi-experimental intervention study was conducted in a 23-bed MICU of a tertiary care hospital in Korea from September 2016 to December 2017. In a prospective, interrupted time-series analysis (ITS) with a 6-month CHG bathing intervention, we compared the acquisition and incidence of VRE and the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Acinetobacter baumannii (CRAB) between the pre-intervention and intervention periods. The primary and secondary outcomes were a change in the acquisition of VRE and incidence of VRE, MRSA, or CRAB between the two periods, respectively. Results All the adult patients admitted to the MICU were enrolled in the pre-intervention (n = 259) and intervention (n = 242). The overall CHG daily bathing compliance rate was 72.5%. In the ITS, there was a significant intervention effect with a 58% decrease in VRE acquisition (95% CI 7.1–82.1%, p = 0.038) following the intervention. However, there was no significant intervention effects on the incidence trend of VRE, MRSA, and CRAB determined by clinical culture between the pre-intervention and intervention periods. Conclusion In this real-world study, we concluded that daily bathing with CHG may be an effective measure to reduce VRE cross-transmission among patients in MICU with a high VRE endemicity.

Abstract An increase in antibiotic usage is considered to contribute to the emergence of antimicrobial resistance. Although experts are counting on the antimicrobial stewardship programs to reduce antibiotic usage, their effect remains uncertain. In this study, we aimed to evaluate the impact of antibiotic usage and forecast the prevalence of hospital-acquired extended spectrum β-lactamase (ESBL)—producing Escherichia coli (E. coli) using time-series analysis. Antimicrobial culture information of E. coli was obtained using a text processing technique that helped extract free-text electronic health records from standardized data. The antimicrobial use density (AUD) of antibiotics of interest was used to estimate the quarterly antibiotic usage. Transfer function model was applied to forecast relationship between antibiotic usage and ESBL-producing E. coli. Of the 1938 hospital-acquired isolates, 831 isolates (42.9%) were ESBL-producing E. coli. Both the proportion of ESBL-producing E. coli and AUD increased over time. The transfer model predicted that ciprofloxacin AUD is related to the proportion of ESBL-producing E. coli two quarters later. In conclusion, excessive use of antibiotics was shown to affect the prevalence of resistant organisms in the future. Therefore, the control of antibiotics with antimicrobial stewardship programs should be considered to restrict antimicrobial resistance.

Abstract Background The massive outbreak of the novel coronavirus disease 2019 (COVID-19) in Daegu city and Gyeongsangbuk-do, Republic of Korea (ROK), caused the exponential increase in new cases exceeding 5000 within 6 weeks. Therefore, the community treatment center (CTC) with a digital health care monitoring system based on the smartphone application and personal health record platform (PHR) was implemented. Thus, we report our experience in one of the CTCs to investigate the role of CTC and the feasibility of the digital health care monitoring system in the COVID-19 pandemic. Methods The Gyeongbuk-Daegu 2 CTC was set up at the private residential facility. Admission criteria were 1) patients

BackgroundThe diagnosis of respiratory viral infections (RVIs) in critically ill patients is important for determining treatment options and adhering to infection-control protocols. However, data on the incidence and occurrence patterns of RVIs are scarce. We investigated the epidemiology and clinical impact of RVIs in critically ill patients.MethodsThis retrospective observational study was conducted in a tertiary hospital in South Korea between November 2014 and September 2020. Adult patients (≥ 18 years of age) who tested positive for an RVI by multiplex polymerase chain reaction (mPCR) and were admitted to the intensive care unit (ICU) were included in the study. Clinical characteristics and outcomes were obtained by reviewing electronic medical records. Pearson's χ2 test and Fisher's exact test, Mann-Whitney U test was used to compare between groups of patients. Trend analysis and the χ2-based Q test was used to analyze test behavior of physicians performing mPCR test.ResultsAmong 22,517 patients admitted to the ICU during the study period, 2,222 (9.9%) underwent mPCR testing for an RVI. The median timing of mPCR testing after ICU admission was 1 day (IQR, 0–2). A total of 335 (15.1%) non-duplicative RVI-positive cases were included in the analysis. The incidence rate of RVIs in ICU patients was 30.45 per 10,000 patient-days. The most frequently detected RVI was influenza A (27.8%), followed by rhinovirus (25.4%). Thirty-two (9.6%) RVI-positive patients were diagnosed with upper respiratory infections, 193 (64.1%) with community-acquired, and 108 (35.9%) with hospital-acquired pneumonia. All-cause mortality and mortality related to respiratory tract infection (RTI) were 30.7% and 22.1%, respectively. The initial presentation of septic shock, requirement for mechanical ventilation, and lymphocytopenia were significant predictors of RTI-related mortality. Of the RVI-positive patients, 151 (45.1%) had nonviral coinfections and presented with higher clinical severity and longer hospital stays than patients infected solely with viral pathogens.ConclusionThe incidence of RVIs in ICU patients is common. ICU patients with RVIs had high mortality and frequently presented with coinfections with nonviral pathogens, which were associated with a higher clinical severity than sole RVI. Increased testing for RVIs will enhance infection-control efforts and improve patient care.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as “not optimal”, 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

Messenger RNA (mRNA) vaccination was developed to mitigate the coronavirus disease 2019 pandemic. However, data on antibody kinetics and factors influencing these vaccines’ immunogenicity are limited. We conducted a prospective study on healthy young adults who received two doses of the mRNA-1273 vaccine at 28-day intervals. After each dose, adverse events were prospectively evaluated, and blood samples were collected. The correlation between humoral immune response and reactogenicity after vaccination was determined. In 177 participants (19–55 years), the geometric mean titers of anti-S IgG antibody were 178.07 and 4409.61 U/mL, while those of 50% neutralizing titers were 479.95 and 2851.67 U/mL four weeks after the first and second vaccine doses, respectively. Anti-S IgG antibody titers were not associated with local reactogenicity but were higher in participants who experienced systemic adverse events (headache and muscle pain). Antipyretic use was an independent predictive factor of a robust anti-SARS-CoV-2 antibody response after receiving both vaccine doses. Systemic reactogenicity after the first dose influenced antibody response after the second dose. In conclusion, mRNA-1273 induced a robust antibody response in healthy young adults. Antipyretic use did not decrease the anti-SARS-CoV-2 antibody response after mRNA-1273 vaccination.

Abstract Background The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has become a global concern for public health. The proximity of vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA) is considered to be one of the foremost risk factors for the development of VRSA. This study aimed to determine the incidence, risk factors, and clinical outcomes of intestinal co-colonization with VRE and MRSA. Methods A case–control study was conducted in 52-bed intensive care units (ICUs) of a university-affiliated hospital from September 2012 to October 2017. Active surveillance using rectal cultures for VRE were conducted at ICU admission and on a weekly basis. Weekly surveillance cultures for detection of rectal MRSA were also conducted in patients with VRE carriage. Patients with intestinal co-colonization of VRE and MRSA were compared with randomly selected control patients with VRE colonization alone (1:1). Vancomycin minimum inhibitory concentrations (MICs) for MRSA isolates were determined by the Etest. Results Of the 4679 consecutive patients, 195 cases and 924 controls were detected. The median monthly incidence and duration of intestinal co-colonization with VRE and MRSA were 2.3/1000 patient-days and 7 days, respectively. The frequency of both MRSA infections and mortality attributable to MRSA were higher in the case group than in the control group: 56.9% vs. 44.1% (P = 0.011) and 8.2% vs. 1.0% (P = 0.002), respectively. Independent risk factors for intestinal co-colonization were enteral tube feeding (odds ratio [OR], 2.09; 95% confidence interval [CI] 1.32–3.32), metabolic diseases (OR, 1.75; 95% CI 1.05–2.93), male gender (OR, 1.62; 95% CI 1.06–2.50), and Charlson comorbidity index

Few studies have focused on clinical courses or viral loads in young asymptomatic or mild patients with COVID-19 infection. We sought to better understand the clinical course and association between viral load and prevalence of pneumonia in young COVID-19 patients with asymptomatic or mild disease severity. In this retrospective study, 106 COVID-19 young patients with asymptomatic or mild disease severity were analyzed for clinical characteristics, clinical course, prevalence of radiologically proven pneumonia and viral load. The cut-off value of viral load for presence of pneumonia was also investigated. The mean age was 28.0±9.3 years. Eleven patients (10.4%) experienced viral remission within one week of diagnosis, but one (0.9%) transferred to the hospital due to aggravation of pneumonia. Patients with pneumonia had significantly higher viral load than those without, and the cut-off value of the Ct value for presence of pneumonia were 31.38. The patients with pneumonia had significantly slower recovery times than those without. Diarrhea was significantly more common in patients with pneumonia than patients without pneumonia. In conclusion, most young asymptomatic and mildly symptomatic patients showed stable clinical course. There were significant differences in viral load and recovery times between patients with and without pneumonia.

Abstract Background Inappropriate use of antibiotics increases resistance and reduces their effectiveness. Despite evidence-based guidelines, antibiotics are still commonly used to treat infections likely caused by respiratory viruses. In this study, we examined the temporal relationships between antibiotic usage and respiratory infections in the Republic of Korea. Methods The number of monthly antibiotic prescriptions and the incidence of acute respiratory tract infections between 2010 and 2015 at all primary care clinics were obtained from the Korean Health Insurance Review and Assessment Service. The monthly detection rates of respiratory viruses, including adenovirus, respiratory syncytial virus, influenza virus, human coronavirus, and human rhinovirus, were collected from Korea Centers for Disease Control and Prevention. Cross-correlation analysis was conducted to quantify the temporal relationship between antibiotic use and respiratory virus activities as well as respiratory infections in primary clinics. Results The monthly use of different classes of antibiotic, including penicillins, other beta-lactam antibacterials, macrolides and quinolones, was significantly correlated with influenza virus activity. These correlations peaked at the 0-month lag with cross-correlation coefficients of 0.45 (p

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection has a high mortality rate, making the development of novel effective antibiotic therapeutic strategies highly critical. Antimicrobial peptides can outperform conventional antibiotics regarding drug resistance and broad-spectrum activity. PapMA, an 18-residue hybrid peptide, containing N-terminal residues of papiliocin and magainin 2, has previously demonstrated potent antibacterial activity. In this study, PapMA analogs were designed by substituting Ala15 or Phe18 with Ala, Phe, and Trp. PapMA-3 with Trp18 showed the highest bacterial selectivity against CRAB, alongside low cytotoxicity. Biophysical studies revealed that PapMA-3 permeabilizes CRAB membrane via strong binding to LPS. To reduce toxicity via reduced antibiotic doses, while preventing the emergence of multi-drug resistant bacteria, the efficacy of PapMA-3 in combination with six selected antibiotics was evaluated against clinical CRAB isolates (C1–C5). At 25% of the minimum inhibition concentration, PapMA-3 partially depolarized the CRAB membrane and caused sufficient morphological changes, facilitating the entry of antibiotics into the bacterial cell. Combining PapMA-3 with rifampin significantly and synergistically inhibited CRAB C4 (FICI = 0.13). Meanwhile, combining PapMA-3 with vancomycin or erythromycin, both potent against Gram-positive bacteria, demonstrated remarkable synergistic antibiofilm activity against Gram-negative CRAB. This study could aid in the development of combination therapeutic approaches against CRAB.

OBJECTIVE: Antimicrobial stewardship programs have been proposed for reducing bacterial resistance in the hospital environment. The purpose of this study was to investigate the impact of a carbapenem-use stewardship program on the susceptibility of Acinetobacter baumannii to Group 2 carbapenems. METHODS: A before and after intervention study was conducted at a university hospital from September 2008 to February 2013. Three study periods were defined: Phase I, pre-intervention (months 1-18); Phase II, a postintervention period during which ertapenem use was mandated but carbapenem use was not restricted (months 19-36); and Phase III, a postintervention period during which Group 2 carbapenem use was restricted (months 37-54). RESULTS: During the study period, intervention resulted in diminished consumption of Group 2 carbapenems (antimicrobial use density (AUD): 21.3±6.0 in Phase I, 18.8±6.0 in Phase II, 16.1±4.4 in Phase III; P = 0.028) and increased consumption of ertapenem (AUD: 2.7±1.7 in Phase I, 7.2±4.5 in Phase II, 9.1±5.3 in Phase III; P

We investigated the Pseudomonas aeruginosa (PA) outer membrane vesicles (OMVs) and their effect on Acinetobacter baumannii (AB) growth in vitro. The inhibitory effects of PA on AB were assessed using a cross-streak assay. The OMVs were extracted through high-speed centrifugation, tangential flow filtration, and ultracentrifugation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM), and nanoparticle tracking assays (NTAs). Proteomic analysis was conducted to compare the OMVs of different PA strains. PA022 exhibited more pronounced inhibition of AB growth compared with PA ATCC 27853. TEM confirmed the presence of OMVs in both PA022 and PA ATCC 27853, revealing phospholipid bilayer structures. The NTA revealed similar sizes and concentrations. Proteomic analysis identified 623 and 538 proteins in PA022 and PA ATCC 27853 OMVs, respectively, with significant proportions of the outer membrane and extracellular proteins, respectively. Importantly, PA022 OMVs contained six known virulence factors and motility-associated proteins. This study revealed the unique characteristics of PA OMVs and their inhibitory effects on AB growth, shedding light on their role in bacterial interactions. Proteomic analysis provides valuable insights into potential pathogenic functions and therapeutic applications against bacterial infections.

This study compared the clinical outcomes and safety of meropenem–colistin versus meropenem–tigecycline in the treatment of adult patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia. A retrospective observational study of patients with CRAB pneumonia was performed at a 1048-bed university-affiliated hospital in the Republic of Korea between June 2013 and January 2020. All adult patients initially treated with meropenem–colistin were compared with those treated with meropenem–tigecycline to evaluate in-hospital mortality and adverse events. Altogether, 66 patients prescribed meropenem–colistin and 24 patients prescribed meropenem–tigecycline were included. All patients had nosocomial pneumonia, and 31.1% had ventilator-associated pneumonia. The minimum inhibitory concentrations of meropenem ≤ 8 μg/mL and tigecycline ≤ 2 μg/mL were 20.0% and 81.1%, respectively. The in-hospital and 28-day mortality rates were 40% and 32%, respectively. In the Cox proportional hazard regression analysis, predictors associated with in-hospital mortality included procalcitonin ≥ 1 ng/mL (adjusted hazard ratio (aHR), 3.39; 95% confidence interval (CI) 1.40–8.19; p = 0.007) and meropenem–colistin combination therapy (aHR, 2.58; 95% CI, 1.07–6.23; p = 0.036). Episodes of nephrotoxicity were significantly more common in the meropenem–colistin group than in the meropenem–tigecycline group (51.5% vs. 12.5%, p = 0.001). Meropenem–tigecycline combination therapy might be a valuable treatment option for patients with CRAB pneumonia.