Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants.

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.

Trends, clinical characteristics, antimicrobial susceptibility patterns, and outcomes of Campylobacter bacteraemia: a multicentre retrospective study.

PURPOSE: We aimed to explore the clinical characteristics of Campylobacter bacteraemia and identify the trends, risk factors for mortality, and antimicrobial susceptibility patterns from clinical samples. METHODS: This retrospective cohort study included patients confirmed to have Campylobacter bacteraemia from seven hospitals between January 2010 and June 2021. Data on demographics and underlying history, clinical manifestation, and antimicrobial susceptibility patterns were collected and analyzed. Annual cases of Campylobacter enteritis were extracted from a public database. RESULTS: A total of 108 patients were included, and five species were isolated. Campylobacter jejuni accounted for 54 (50.0%) cases and 17 (16%) patients had no symptoms other than fever. In-hospital mortality occurred in 14 (13.0%) patients. C. jejuni bacteraemia was associated with lower mortality compared to non-C. jejuni bacteraemia. Underlying cancer and septic shock were the significant factors associated with in-hospital mortality. Quinolone resistance was high (59%), whereas only 4% of isolates exhibited macrolide resistance. There has been a significant increase in the number of Campylobacter enteritis cases, which was strongly correlated with the number of Campylobacter bacteraemia cases (Pearson's coefficient: 0.953; p < 0.0001). CONCLUSION: The notably increasing incidence of Campylobacter bacteraemia and antibiotic resistance patterns can challenge the treatment, necessitating collective efforts of national surveillance and networks by many departments.

Differences of clinical characteristics and outcome in proven invasive Trichosporon infections caused by asahii and non-asahii species.

BACKGROUND: Trichosporon is an emerging yeast that causes invasive infections in immunocompromised patients experiencing prolonged hospitalisation, indwelling venous catheters and neutropenia. METHODS: This retrospective observational cohort study analysed invasive Trichosporon infections (ITIs) occurring between January 2005 and December 2022 at three tertiary hospitals and compared the clinical characteristics and prognostic factors of ITIs caused by Trichosporon asahii and non-T. asahii spp. After evaluating 1067 clinical isolates, we identified 46 patients with proven ITIs, defined as cases in which Trichosporon was isolated from blood, cerebrospinal fluid, or sterile tissues. RESULTS: The patients were separated into T. asahii and non-T. asahii groups containing 25 and 21 patients, respectively, all of which except one were immunocompromised. During this period, both the number of clinical isolates and patients with ITIs (mainly T. asahii) increased; whereas, cases involving non-T. asahii spp. decreased. Compared with the non-T. asahii group, the T. asahii group had more patients with multiple catheters (84% vs. 33%, p = .001) and those receiving renal replacement therapy (48% vs. 14%, p = .005). The all-cause 28-day mortality rate after ITI in the T. asahii group (44%) was significantly higher than in the non-T. asahii group (10%, Log-rank p = .014). The multivariate Cox regression model revealed that T. asahii (reference, non-T. asahii spp.; aHR = 4.3; 95% CI = 1.2-15.2, p = .024) and neutropenia for 5 days or more (aHR = 2.2, 95% CI = 1.5-3.6, p = .035) were independent factors in the 28-day mortality after ITI. CONCLUSION: The proven ITIs due to T. asahii produced more unfavourable outcomes compared with ITIs caused by non-T. asahii spp.

Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species.

BACKGROUND: Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. METHODS: A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. RESULTS: A total of 37 patients were enrolled-26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. CONCLUSIONS: In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

A Modified Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Mean Platelet Volume-to-Platelet Count to Predict 28-Day Mortality in Patients With Sepsis.

BACKGROUND: Recently, a new scoring system was developed that uses the red blood cell distribution width (RDW), delta neutrophil index (DNI), and platelet count (PC) to predict mortality in patients with sepsis. We investigated whether a modified simple scoring system based on the RDW, DNI, and mean platelet volume-to-PC (MPV/PC) ratio could predict the mortality of patients with sepsis, and compared it to the previous scoring system. METHODS: We conducted a retrospective cohort study of 264 adults who had been treated for sepsis in an emergency department between January 2016 and February 2019. Each patient was rated on a scale of 0 to 3 according to the modified scoring system. Point values were assigned based on RDW > 14.5%, DNI > 5.0%, and MPV/PC ratio >10.1. RESULTS: The 28-day mortality rate was 14.4%. Those who died had higher scores than those who survived (mean: 1.55 ± 0.92 vs 0.93 ± 0.78, P < .001). The area under the curve for the new scoring system was higher than that of the previous scoring system (0.685 vs 0.645). CONCLUSION: The modified scoring system was a good predictor of the 28-day mortality and was more useful than the previous scoring system for predicting mortality in patients with sepsis.

Risk factors for mortality in patients with Stenotrophomonas maltophilia bacteremia and clinical impact of quinolone-resistant strains.

BACKGROUND: Stenotrophomonas maltophilia is an important nosocomial pathogen. This pathogen has intrinsic or acquired resistance to a number of antibiotics classes. Furthermore, Stenotrophomonas infections have been associated with high mortality, mainly in immunocompromised patients. Accordingly, we conducted a retrospective cohort study on the clinical data, microbiological characteristics, and outcomes of patients with S. maltophilia (SM) bacteremia. METHODS: A retrospective cohort study was conducted at two tertiary care referral hospitals in Seoul, South Korea. Data were collected between January 2006 and December 2015 from electric medical records. Our analysis aimed to identify the risk factors associated with crude mortality, as well as the predictive factors of quinolone-resistant strains in SM bacteremia patients. RESULTS: A total of 126 bacteremia patients were enrolled in the study. The mortality rate was 65.1%. On multivariable analysis, hypoalbuminemia (odds ratio [OR], 5.090; 95% confidence interval [CI], 1.321-19.621; P = 0.018), hematologic malignancy (OR, 35.567; 95% CI, 2.517-502.515; P = 0.008) and quinolone-resistant strains (OR, 7.785; 95% CI, 1.278-47.432; P = 0.026) were independent risk factors for mortality. Alternatively, usage of an empirical regimen with quinolone (OR, 0.172; 95% CI, 0.034-0.875; P = 0.034) was an independent protective factor for mortality. The multivariable analysis of predictive factors revealed that high Charlson comorbidity index (OR, 1.190; 95% CI, 1.040-1.361; P = 0.011) and indwelling of a central venous catheter (CVC) (OR, 3.303; 95% CI, 1.194-9.139; P = 0.021) were independent predisposing factors associated with quinolone-resistant strains in SM bacteremia patients. CONCLUSIONS: Our findings suggest that a high Charlson comorbidity score and indwelling of a CVC were significantly independent predictors of quinolone-resistant strains in SM bacteremia patients. Therefore, we need to carefully consider the antibiotic use in SM bacteremia patients with these predictive factors.

A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock.

PURPOSE: The purpose of our study was to investigate whether a simple scoring system based on the red blood cell distribution width (RDW), delta neutrophil index (DNI), and platelet count was associated with the prognosis of patients with sepsis, and whether this scoring system was more useful than each individual parameter. MATERIALS AND METHODS: We conducted a retrospective cohort study involving adult patients who received intensive therapy due to severe sepsis and septic shock from January 2010 to December 2015 at a tertiary teaching hospital in South Korea. RESULTS: A total of 730 patients were included in this study. Each patient was rated on a scale of 0 to 3 according to the new scoring system using the platelet count, RDW, and DNI. Point values were assigned based on the following definitions: RDW > 14.5%, DNI > 5.0%, and platelet count < 150 000/mm3. The 28-day mortality rate was 12.6% (92/730). The nonsurvivors had higher scores than the survivors (2.05 ± 0.80 vs 1.06 ± 0.87, P < .001). In the multivariate Cox proportional hazard analysis, the scoring system was an independent predictor of the 28-day mortality. The scoring system was well calibrated (P = .81 for the goodness-of-fit test) and discriminated (area under the receiver operating characteristic curve = 0.785). CONCLUSION: Our new scoring system using the RDW, DNI, and platelet count was useful for predicting the mortality in patients with severe sepsis and septic shock.

Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter pylori eradication.

Objectives: Novel antibacterial strategies against Helicobacter pylori are needed because H. pylori strains are acquiring resistance to antibiotics. We evaluated the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment regimens in a murine model of H. pylori infection. Methods: Two groups of 10 rats were administered either smectite or S-GEN to measure coverage of the gastric mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups of 10 mice each given different treatments, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces. The levels of proinflammatory cytokines were examined. Results: S-GEN was retained in the gastric mucosal layer with a >60% distribution ratio for up to 1 h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared with that of untreated mice or mice treated with other regimens. The cure rates in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%, 60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the faeces of mice were 90% and 100% in Group III with standard therapy and Group V with triple therapy including S-GEN, respectively. S-GEN triple therapy also reduced the levels of proinflammatory cytokines. Conclusions: These results suggest that S-GEN is a promising and effective therapeutic agent for the treatment of H. pylori infection.

Impact of matrix-assisted laser desorption/ionization time of flight mass spectrometric evaluation on the clinical outcomes of patients with bacteremia and fungemia in clinical settings lacking an antimicrobial stewardship program: a pre-post quasi experimental study.

BACKGROUNDS: Several studies have evaluated the impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined with antimicrobial stewardship in patients with positive blood cultures; clinical outcomes improved. However, in many hospitals, antimicrobial stewardship is not available because of restricted medical resources. Thus, we investigated the impact of evaluation by MALDI-TOF MS on the clinical outcomes of patients with bacteremia and fungemia treated in a clinical setting lacking an antimicrobial stewardship program (ASP). METHODS: We designed a pre-post quasi experimental study and retrospectively reviewed the medical records of patients aged > 18 years old with bacteremia and fungemia during two periods: October-December 2012 and October-December 2013. Conventional methods were used to detect microbial pathogens in 2012, and MALDI-TOF MS was employed in 2013. Clinical outcomes compared between periods were the time to pathogen identification, time to effective therapy, 30-day all-cause mortality, time to microbiological clearance, length of ICU stay, and rate of recurrence of the same bloodstream infection (BSI). RESULTS: A total of 556 patients were enrolled; 302 patients in 2012, and 254 in 2013. The use of MALDI-TOF MS without an ASP reduced the time to pathogen identification (86.4 vs. 63.5 h, P < 0.001) but did not significantly reduce the time to effective therapy (27.4 vs. 23.2 h, P = 0.187). Also, none of the following differed significantly between the two periods: mortality (17.5 vs. 15.7%, P = 0.571), the time to microbiological clearance (3.6 vs. 3.7 days, P = 0.675), the length of ICU stay (16.8 vs. 14.7 days, P = 0.706), and the recurrence rate of the same BSI (5.0 vs. 2.8%, P = 0.183). CONCLUSIONS: The use of MALDI-TOF MS alone in a setting lacking an ASP did not afford clinical benefits. An ASP combined with MALDI-TOF MS is necessary to improve clinical outcomes.

Comparison of the efficacy of nafcillin and glycopeptides as definitive therapy for patients with methicillin-susceptible Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.

Chronic kidney disease with genitourinary tuberculosis: old disease but ongoing complication.

BACKGROUND: Genitourinary tuberculosis (GUTB) is a type of extrapulmonary TB that exerts a deleterious effect on renal function by promoting renal calcification and ureteric stricture. Therefore, we investigated the risk factors for chronic kidney disease (CKD) in GUTB patients after the end of treatment. METHODS: This retrospective study was conducted at a tertiary hospital in South Korea. Data from patients (>18 years of age) with GUTB were collected from January 2005 to July 2016. CKD was defined as a glomerular filtration rate <60 mL/min/1.73m2 after the end of treatment. RESULTS: In total, 56 patients with GUTB (46.4% males; mean age 52.8 ± 16.6 years) were enrolled in the study. CKD developed in 11 (19.6%) patients and end-stage renal disease in 4 (7.1%). In a univariate analysis, older age (p = 0.029), microscopic haematuria (p = 0.019), proteinuria (p = 0.029), acute renal failure (ARF) (p < 0.001) and a positive polymerase chain reaction-based test result for TB in the urine (p = 0.030) were significantly associated with decreased renal function. In a multivariate analysis, ARF (odds ratio [OR], 54.31; 95% confidence interval [CI], 1.52-1944.00; p = 0.032) and old age (OR, 54.26; 95% CI, 1.52-1932.94; p = 0.028) were independent risk factors for CKD in GUTB patients. CONCLUSIONS: ARF and old age were independent risk factors for CKD in GUTB patients. Therefore, in elderly GUTB patients with ARF at the time of diagnosis, regular follow-up of renal function should be performed even after the end of treatment.

The impact of production of extended-spectrum ß-lactamases on the 28-day mortality rate of patients with Proteus mirabilis bacteremia in Korea.

BACKGROUND: The incidence of Proteus mirabilis antimicrobial resistance, especially that mediated by extended-spectrum ß-lactamases (ESBLs), has increased. We investigated the impact of ESBL production on the mortality of patients with P. mirabilis bacteremia in Korea. METHODS: Patients diagnosed with P. mirabilis bacteremia between November 2005 and December 2013 at a 2000-bed tertiary care center in South Korea were included in this study. Phenotypic and molecular analyses were performed to assess ESBL expression. Characteristics and treatment outcomes were investigated among ESBL-producing and non-ESBL-producing P. mirabilis bacteremia groups. A multivariate analysis of 28-day mortality rates was performed to evaluate the independent impact of ESBLs. RESULTS: Among 62 P. mirabilis isolates from 62 patients, 14 expressed ESBLs (CTX-M, 2; TEM, 5; both, 6; other, 1), and the 28-day mortality rate of the 62 patients was 17.74%. No clinical factor was significantly associated with ESBL production. The 28-day mortality rate in the ESBL-producing group was significantly higher than that in the non-ESBL-producing group (50% vs. 8.3%, p = 0.001). A multivariate analysis showed that ESBL production (odds ratio [OR], 11.53, 95% confidence interval [CI], 2.11-63.05, p = 0.005) was independently associated with the 28-day mortality rate in patients with P. mirabilis bacteremia. CONCLUSIONS: ESBL production is significantly associated with mortality in patients with bacteremia caused by P. mirabilis. Rapid detection of ESBL expression and prompt appropriate antimicrobial therapy are required to reduce mortality caused by P. mirabilis bacteremia.

Predictive factors for unfavorable outcomes of tuberculous pericarditis in human immunodeficiency virus-uninfected patients in an intermediate tuberculosis burden country.

BACKGROUND: In areas where Mycobacterium tuberculosis is endemic, tuberculosis is known to be the most common cause of pericarditis. However, the difficulty in diagnosis may lead to late complications such as constrictive pericarditis and increased mortality. Therefore, identification of patients at a high risk for poor prognosis, and prompt initiation of treatment are important in the outcome of TB pericarditis. The aim of this study is to identify the predictive factors for unfavorable outcomes of TB pericarditis in HIV-uninfected persons in an intermediate tuberculosis burden country. METHODS: A retrospective review of 87 cases of TB pericarditis diagnosed at a tertiary referral hospital in South Korea was performed. Clinical characteristics, treatment outcomes, complications during treatment, duration of treatment, and medication history were reviewed. Unfavorable outcome was defined as constrictive pericarditis identified on echocardiography performed 3 to 6 months after initial diagnosis of TB pericarditis, cardiac tamponade requiring emergency pericardiocentesis, or death. Predictive factors for unfavorable outcomes were identified. RESULTS: Of the 87 patients, 44 (50.6%) had unfavorable outcomes; cardiac tamponade (n = 36), constrictive pericarditis (n = 18), and mortality (n = 4). 14 patients experienced both cardiac tamponade and constrictive pericarditis. During a 1 year out-patient clinic follow up, 4 patients required repeat pericardiocentesis and pericardiectomy was performed in 0 patients. In the multivariate analysis, patients with large amounts of pericardial effusion (P = .003), those with hypoalbuminemia (P = .011), and those without cardiovascular disease (P = .011) were found to have a higher risk of unfavorable outcomes. CONCLUSION: HIV-uninfected patients with TB pericarditis are at a higher risk for unfavorable outcomes when presenting with low serum albumin, with large pericardial effusions, and without cardiovascular disease.

Delaying diagnostic procedure significantly increases mortality in patients with invasive mucormycosis.

Invasive mucormycosis is an uncommon but increasing life-threatening fungal infection. The present study investigated clinical characteristics and mortality among patients diagnosed as invasive mucormycosis infection. We retrospectively reviewed a total of 24 histologically proven cases of invasive mucormycosis at two tertiary care referral hospitals between November 2005 and February 2014. Overall survival was 50% (n = 12). The time between onset of symptom and diagnostic procedure proved to be associated with mortality (P = 0.009). In addition, preexisting renal failure and thrombocytopenia demonstrated trends toward a poor outcome in our study (P = 0.089 and 0.065, respectively). On multivariate regression analysis, delayed diagnostic procedure (more than 16 days after the onset of symptoms) was an independent predictor of mortality (OR= 12.34, 95% CI, 1.43-10.64; P = 0.022). Mucormycosis is a destructive fungal infection that is associated with high mortality rates, ranging from 40% to 100% depending on the form of disease. When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease.

Incidence and risk factors for carbapenem- and multidrug-resistant Acinetobacter baumannii bacteremia in hematopoietic stem cell transplantation recipients.

BACKGROUND: Bacteremia with multidrug-resistant (MDR) Acinetobacter baumannii with carbapenem resistance is an important healthcare-associated infection that increases morbidity and mortality in immunocompromised patients. The aim of this study was to assess the annual incidence and clinical characteristics of such bacteremia and to identify the risk factors for infection in hematopoietic stem cell transplantation (HSCT) recipients. METHODS: A retrospective cohort and case-control study was conducted in 483 HSCT recipients between January 2005 and December 2011 at a single tertiary center. Thirty-eight control HSCT patients without evidence of post-transplant infection were matched with 19 patients with bacteremia due to MDR A. baumannii in a 2:1 ratio. RESULTS: The total incidence of carbapenem-resistant-MDR A. baumannii bacteremia was 0.52 cases/10,000 patient-days. In most cases (17 of 19, 89.5%), bacteremia developed after engraftment. Pneumonia was the origin of bacteremia in all patients. Eighteen (94.7%) patients with bacteremia and 3 (8.3%) without bacteremia died. In multivariate regression analyses, the duration between admission and HSCT (odds ratio (OR) 2.19 per 1-day increase, p = 0.030) and a history of care in an intensive care unit after HSCT (OR 32.2, p = 0.021) were independent risk factors for the development of carbapenem-resistant-MDR A. baumannii bacteremia. CONCLUSIONS: We report that carbapenem-resistant-MDR A. baumannii bacteremia in HSCT recipients is a fatal infectious complication and mainly develops after engraftment.

Active tuberculosis risk with tumor necrosis factor inhibitors after treating latent tuberculosis.

BACKGROUND: Active tuberculosis (TB) risk increases during anti-tumor necrosis factor (TNF) therapy; therefore, latent TB infection (LTBI) screening is recommended in potential TNF inhibitor users. It is unclear whether anti-TNF therapy increases the risk of active TB infection even after standard LTBI treatment. OBJECTIVE: The objective of this study was to compare the risk of active TB development in LTBI-positive versus LBTI-negative TNF inhibitor users following the current national LTBI treatment guidelines for LTBI. METHODS: We retrospectively studied 949 TNF inhibitor users with immune-mediated inflammatory diseases from 2005 to 2012 at the Yonsei University Health System. We compared the incidence of active TB among LTBI-positive TNF inhibitor users treated according to national guidelines (n = 256) and LTBI-negative TNF inhibitor users (n = 521), using Poisson regression. RESULTS: The active TB incidence was 1107 per 100,000 patient-years in LTBI-positive TNF inhibitor users who received standard LTBI treatment and 490 per 100,000 patient-years in LTBI-negative TNF inhibitor users. Analysis showed that despite this numerical trend active TB risk was not statistically significantly elevated in LTBI-positive versus LTBI-negative TNF inhibitor users (incidence risk ratio, 2.15; P = 0.24; 95% confidence interval, 0.6-7.7). CONCLUSIONS: This study demonstrated no statistically significantly increased risk of active TB in LTBI-positive TNF inhibitor users who received standard LTBI treatment compared with LTBI-negative TNF inhibitor users.

Shift in risk factors for mortality by period of the bloodstream infection timeline.

BACKGROUND: This study was designed to determine changes in risk factors on the prognosis of patients during each period of the bloodstream infection (BSI) timeline. METHODS: Through an integrated study of multivariable regressions with machine learning techniques, the risk factors for mortality during each period of BSI were analyzed. RESULTS: A total of 302,303 inpatients who underwent blood cultures during 2011-2021 were enrolled. More than 8 % of BSI cases progressed to subsequent BSI, and risk factors were identified as gut colonization with vancomycin-resistant enterococci (aOR 1.82; 95 % CI 1.47-2.24), intensive care unit admission (aOR 3.37; 95 % CI 3.35-4.28), and current cancer chemotherapy (aOR 1.54; 95 % CI 1.36-1.74). The mean SOFA score of the deceased patients during the first 7 days was 10.6 (SD 4.3), which was significantly higher than those on days 8-30 (7.0 ± 4.2) and after Day 30 (4.0 ± 3.5). BSIs caused by Acinetobacter baumannii and Candida albicans were more likely to result in deaths of patients for all time periods (all, P < 0.001). BSIs caused by Enterococcus faecalis and Enterococcus faecium were associated with a poor outcome in the period after Day 30 (both, P < 0.001). Nonsusceptible phenotypes to ß-lactam/ß-lactamase inhibitors of Escherichia coli and Klebsiella pneumoniae influenced the prognoses of patients with BSI in terms of high mortality rates during both days 8-30 and after Day 30. CONCLUSION: Influence of microbiological factors on mortality, including BSI-causative microorganisms and their major antimicrobial resistance, was emphasized in both periods of days 8-30 and after Day 30.

Physical Activity and the incidence of sepsis: A 10-year observational study among 4 million adults.

BACKGROUND: As the group at high risk for sepsis is increasing with the aging of the population, physical activity (PA), which has beneficial effects on various diseases, needs to be considered as a personalized prevention strategy for sepsis without direct anti-sepsis drug. PURPOSE: To examine the association between the amount of PA (based on intensity, duration, and frequency) and the incidence rates of sepsis and mortality after sepsis. METHODS: This was a large-scale, retrospective, longitudinal cohort study using data from the Korean National Health Insurance Service and the biennial general health screening program. The amount of PA self-reported at the time of the health screening was categorized as non-PA, mild (<500 metabolic equivalents [METs]-Min/Week), moderate (500-1000), severe (1000-1500), and extreme (≥1500). The multivariable regression model was adjusted for age, sex, income, body mass index, smoking, alcohol consumption, diabetes, hypertension, dyslipidemia, and chronic diseases. RESULTS: From 4,234,415 individuals who underwent a health screening in 2009, 3,929,165 subjects were selected after exclusion for wash-out period and a 1-year lag period, and then observed for the event of sepsis or all-cause death until December 2020. During a median 10.3 years of follow-up, 83,011 incidents of sepsis were detected. The moderate-PA group showed the lowest incidence (1.56/1000 person-years) and risk for sepsis, with an adjusted hazard ratio (aHR) of 0.73 (95% CI, 0.72-0.75, P < 0.001) compared with the non-PA group. The occurrence of sepsis among people aged ≥65 years and ex-smokers were significantly lower in the moderate-PA group (aHR; 0.77, 95% CI; 0.74-0.79; and 0.68, 0.64-0.71, respectively, Ps < 0.001). The long-term all-cause mortality after sepsis was significantly lower in the PA group than in the non-PA group (overall P = 0.003). CONCLUSIONS: Physical activity is associated with a lower risk of sepsis, especially in elderly people who have the highest incidence of sepsis. The protective effects of aerobic PA on sepsis might need to be incorporated with other interventions in sepsis guidelines through the accumulation of future studies.

Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants.

Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.