Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV.

BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

Pre-existing humoral immunity and CD4+ T cell response correlate with cross-reactivity against SARS-CoV-2 Omicron subvariants after heterologous prime-boost vaccination.

BACKGROUND: Information regarding the heterologous prime-boost COVID vaccination has been fully elucidated. The study aimed to evaluate both humoral, cellular immunity and cross-reactivity against variants after heterologous vaccination. METHODS: We recruited healthcare workers previously primed with Oxford/AstraZeneca ChAdOx1-S vaccines and boosted with Moderna mRNA-1273 vaccine boost to evaluate the immunological response. Assay used: anti-spike RBD antibody, surrogate virus neutralizing antibody and interferon-γ release assay. RESULTS: All participants exhibited higher humoral and cellular immune response after the booster regardless of prior antibody level, but those with higher antibody level demonstrated stronger booster response, especially against omicron BA.1 and BA.2 variants. The pre-booster IFN-γ release by CD4+ T cells correlates with post-booster neutralizing antibody against BA.1 and BA.2 variant after adjustment with age and gender. CONCLUSIONS: A heterologous mRNA boost is highly immunogenic. The pre-existing neutralizing antibody level and CD4+ T cells response correlates with post-booster neutralization reactivity against the Omicron variant.

Antibody Profiling of Dengue Severities Using Flavivirus Protein Microarrays.

Dengue is a viral disease transmitted by Aedes aegypti mosquitoes. According to the World Health Organization, about half of the world's population is at risk of dengue. There are four serotypes of the dengue virus. After infection with one serotype, it will be immune to such a serotype. However, subsequent infection with other serotypes will increase the risk of severe outcomes, e.g., dengue hemorrhagic fever, dengue shock syndrome, and even death. Since severe dengue is challenging to predict and lacks molecular markers, we aim to build a multiplexed Flavivirus protein microarray (Flaviarray) that includes all of the common Flaviviruses to profile the humoral immunity and cross-reactivity in the dengue patients with different outcomes. The Flaviarrays we fabricated contained 17 Flavivirus antigens with high reproducibility (R-square = 0.96) and low detection limits (172-214 pg). We collected serums from healthy subjects (n = 36) and dengue patients within 7 days after symptom onset (mild dengue (n = 21), hospitalized nonsevere dengue (n = 29), and severe dengue (n = 36)). After profiling the serum antibodies using Flaviarrays, we found that patients with severe dengue showed higher IgG levels against multiple Flavivirus antigens. With logistic regression, we found groups of markers with high performance in distinguishing dengue patients from healthy controls as well as hospitalized from mild cases (AUC > 0.9). We further reported some single markers that were suitable to separate dengue patients from healthy controls (AUC > 0.9) and hospitalized from mild outcomes (AUC > 0.8). Together, Flaviarray is a valuable tool to profile antibody specificities, uncover novel markers for decision-making, and shed some light on early preventions and treatments.

In Vitro and In Vivo Antimicrobial Activities of Vancomycin and Rifampin against Elizabethkingia anophelis.

Elizabethkingia anophelis has emerged as a critical human pathogen, and a number of isolated reports have described the successful treatment of Elizabethkingia infections with vancomycin, a drug that is typically used to target Gram-positive bacteria. This study employed in vitro broth microdilution checkerboard and time-kill assays, as well as in vivo zebrafish animal models to evaluate the individual and combination antimicrobial effects of vancomycin and rifampin against E. anophelis. The minimum inhibitory concentration ranges of vancomycin and rifampin against 167 isolates of E. anophelis were 16-256 mg/L and 0.06-128 mg/L, respectively. The checkerboard assay results revealed a synergistic effect between vancomycin and rifampin in 16.8% (28/167) of the isolates. Time-kill assays were implemented for 66 isolates, and the two-drug combination had a synergistic interaction in 57 (86.4%) isolates. In vivo zebrafish studies revealed that treatment with vancomycin monotherapy, rifampin monotherapy, or vancomycin-rifampin combination therapy yielded a higher survival rate than the control group treatment with 0.9% saline. The results of this study support the use of vancomycin to treat E. anophelis infections.

Mutant Prevention Concentrations of Ciprofloxacin and Levofloxacin and Target Gene Mutations of Fluoroquinolones in Elizabethkingia anophelis.

Fluoroquinolones are potentially effective against Elizabethkingia anophelis. We investigated the MIC, mutant prevention concentration (MPC), and target gene mutations of fluoroquinolones in E. anophelis. Eighty-five E. anophelis isolates were collected from five hospitals in Taiwan. The MIC and MPC of ciprofloxacin and levofloxacin were examined for all E. anophelis except 17 isolates, in which ciprofloxacin MPC could not be determined due to drug precipitation caused by overly high drug concentration. Mutations in the quinolone resistance-determining regions of DNA gyrase (GyrA and GyrB) and topoisomerase IV (ParC and ParE) in the clinical isolates and fluoroquinolone-selected mutants were examined. Overall, 23.5% and 71.8% of the isolates tested were susceptible to ciprofloxacin and levofloxacin, respectively. The MPC50 of ciprofloxacin was 128 mg/L, and the MPC50 of levofloxacin was 51.2 mg/L. The MPC50/MIC50 ratio for ciprofloxacin was 64, whereas that for levofloxacin was 25.6. The coefficient of determination between the MPC and MIC for ciprofloxacin and levofloxacin was 0.72 and 0.56, respectively, in the linear regression analysis. Preexisting mutations in GyrA (S83I, S83R, and D87Y) were identified in 18 clinical isolates, all of which were resistant to both ciprofloxacin and levofloxacin. Additional amino acid substitutions in GyrA were identified in all ciprofloxacin- and levofloxacin-selected mutants. Furthermore, GyrB alterations (D431N or D431H) were found in nine levofloxacin-treated isolates. Given that maintaining the serum concentrations of fluoroquinolones above MPCs is impossible under presently recommended doses, the selection of mutant E. anophelis strains seems inevitable.

The occurrence of and risk factors for developing acute critical illness during quarantine as a response to the COVID-19 pandemic.

BACKGROUND/PURPOSE: Early detection and timely quarantine measures are necessary to control disease spread and prevent nosocomial outbreaks of Coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the impact of a quarantine strategy on patient safety and quality of care. METHODS: This retrospective cohort study enrolled patients admitted to the quarantine ward in a tertiary hospital in southern Taiwan. The incidence and causes of acute critical illness, including clinical deterioration and unexpected complications during the quarantine period, were reviewed. Further investigation was performed to identify risk factors for acute critical illness during quarantine. RESULTS: Of 320 patients admitted to the quarantine ward, more than two-thirds were elderly, and 37.8% were bedridden. During the quarantine period, 68 (21.2%) developed acute critical illness, which more commonly occurred among patients older than 80 years and with a bedridden status, nasogastric tube feeding, or dyspnea symptoms. Bedridden status was an independent predictor of acute critical illness. Through optimization of sampling for COVID-19 and laboratory schedules, both the duration of quarantine and the proportion of acute critical illness among bedridden patients during quarantine exhibited a decreasing trend. There was no COVID-19 nosocomial transmission during the study period. CONCLUSION: The quarantine ward is a key measure to prevent nosocomial transmission of COVID-19 but may carry a potential negative impact on patient care and safety. For patients with multiple comorbidities and a bedridden status, healthcare workers should remain alert to rapid deterioration and unexpected adverse events during quarantine.

Application of an Artificial Intelligence Trilogy to Accelerate Processing of Suspected Patients With SARS-CoV-2 at a Smart Quarantine Station: Observational Study.

BACKGROUND: As the COVID-19 epidemic increases in severity, the burden of quarantine stations outside emergency departments (EDs) at hospitals is increasing daily. To address the high screening workload at quarantine stations, all staff members with medical licenses are required to work shifts in these stations. Therefore, it is necessary to simplify the workflow and decision-making process for physicians and surgeons from all subspecialties. OBJECTIVE: The aim of this paper is to demonstrate how the National Cheng Kung University Hospital artificial intelligence (AI) trilogy of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm improves medical care and reduces quarantine processing times. METHODS: This observational study on the emerging COVID-19 pandemic included 643 patients. An "AI trilogy" of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm on a tablet computer was applied to shorten the quarantine survey process and reduce processing time during the COVID-19 pandemic. RESULTS: The use of the AI trilogy facilitated the processing of suspected cases of COVID-19 with or without symptoms; also, travel, occupation, contact, and clustering histories were obtained with the tablet computer device. A separate AI-mode function that could quickly recognize pulmonary infiltrates on chest x-rays was merged into the smart clinical assisting system (SCAS), and this model was subsequently trained with COVID-19 pneumonia cases from the GitHub open source data set. The detection rates for posteroanterior and anteroposterior chest x-rays were 55/59 (93%) and 5/11 (45%), respectively. The SCAS algorithm was continuously adjusted based on updates to the Taiwan Centers for Disease Control public safety guidelines for faster clinical decision making. Our ex vivo study demonstrated the efficiency of disinfecting the tablet computer surface by wiping it twice with 75% alcohol sanitizer. To further analyze the impact of the AI application in the quarantine station, we subdivided the station group into groups with or without AI. Compared with the conventional ED (n=281), the survey time at the quarantine station (n=1520) was significantly shortened; the median survey time at the ED was 153 minutes (95% CI 108.5-205.0), vs 35 minutes at the quarantine station (95% CI 24-56; P<.001). Furthermore, the use of the AI application in the quarantine station reduced the survey time in the quarantine station; the median survey time without AI was 101 minutes (95% CI 40-153), vs 34 minutes (95% CI 24-53) with AI in the quarantine station (P<.001). CONCLUSIONS: The AI trilogy improved our medical care workflow by shortening the quarantine survey process and reducing the processing time, which is especially important during an emerging infectious disease epidemic.

Aeromonas Isolates from Fish and Patients in Tainan City, Taiwan: Genotypic and Phenotypic Characteristics.

The present study aimed to isolate Aeromonas from fish sold in the markets as well as in sushi and seafood shops and compare their virulence factors and antimicrobial characteristics with those of clinical isolates. Among the 128 fish isolates and 47 clinical isolates, Aeromonas caviae, A. dhakensis, and A. veronii were the principal species. A. dhakensis isolates carried at least 5 virulence genes, more than other Aeromonas species. The predominant genotype of virulence genes was hlyA lip alt col ela in both A. dhakensis and A. hydrophila isolates, alt col ela in A. caviae isolates, and act in A. veronii isolates. A. dhakensis, A. hydrophila, and A. veronii isolates more often exhibited hemolytic and proteolytic activity and showed greater virulence than A. caviae isolates in Caenorhabditis elegans and the C2C12 cell line. However, the link between the genotypes and phenotypes of the studied virulence genes in Aeromonas species was not evident. Among the four major clinical Aeromonas species, nearly all (99.0%) A. dhakensis, A. hydrophila, and A. veronii isolates harbored blaCphA, which encodes a carbapenemase, but only a minority (6.7%, 7/104) were nonsusceptible to carbapenem. Regarding AmpC ß-lactamase genes, blaAQU-1 was exclusively found in A. dhakensis isolates, and blaMOX3 was found only in A. caviae isolates, but only 7.6% (n = 6) of the 79 Aeromonas isolates carrying blaAQU-1 or blaMOX3 exhibited a cefotaxime resistance phenotype. In conclusion, fish Aeromonas isolates carry a variety of combinations of virulence and ß-lactamase resistance genes and exhibit virulence phenotypes and antimicrobial resistance profiles similar to those of clinical isolates.IMPORTANCEAeromonas species can cause severe infections in immunocompromised individuals upon exposure to virulent pathogens in the environment, but the characteristics of environmental Aeromonas species remain unclear. Our study showed that several pathogenic Aeromonas species possessing virulence traits and antimicrobial resistance similar to those of Aeromonas isolates causing clinical diseases were present in fish intended for human consumption in Tainan City, Taiwan.

Effects of Blue-Light-Induced Free Radical Formation from Catechin Hydrate on the Inactivation of Acinetobacter baumannii, Including a Carbapenem-Resistant Strain.

Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. In particular, the detection of a superoxide anion radical (O2•−), a reactive oxygen species (ROS), and the inactivation of Acinetobacter baumannii (A. baumannii)­including a carbapenem-resistant A. baumannii (CRAB)­was investigated during the photoreaction of catechin hydrate. Following basification with blue light irradiation, the transparent solution of catechin hydrate turned yellowish, and a chromogenic catechin dimer was separated and identified as a proanthocyanidin. Adding ascorbic acid during the photolytic treatment of catechin hydrate decreased the dimer formation, suggesting that ascorbic acid can suppress the photosensitive oxidation of catechin. When catechin hydrate was irradiated by blue light in an alkaline solution, O2•− was produced via photosensitized oxidation, enhancing the inactivation of A. baumannii and CRAB. The present findings on the photon-induced oxidation of catechin hydrate provides a safe practice for the inactivation of environmental microorganisms.

High-dose calcineurin inhibitor-free everolimus as a maintenance regimen for heart transplantation may be a risk factor for Pneumocystis pneumonia.

BACKGROUND: Everolimus reduces the incidence of cardiac-allograft vasculopathy (CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We evaluated the safety of CNI-free everolimus for post-heart transplant (HTx) patients. METHODS: We retrospectively reviewed the records of 36 consecutive patients who had undergone an HTx between January 2006 and December 2013 in National Cheng Kung University Hospital. All patients initially had been treated with the standard tacrolimus regimen. The Study group-12 patients with CAV, renal impairment, or a history of malignancy-were switched from tacrolimus to everolimus. The Control group consisted of 19 patients who remained on the standard regimen. The target everolimus trough concentration was 8-14 ng/mL. The primary outcome was survival, and the secondary outcomes were bacterial, viral, fungal, and other infections; Pneumocystis jirovecii pneumonia (PJP); and rejection (≥2R). RESULTS: During a 53.3±25.6-month follow-up, the survival rate, rejection rate, and number of infections, except for PJP, were not significantly different between the two groups. In the Study group, 6 patients were diagnosed with PJP 33±18.2 months after switching. None of the Control group patients were diagnosed with PJP during follow-up. CONCLUSIONS: A high-dose CNI-free everolimus maintenance regimen might yield a higher incidence of post-transplantation PJP.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates.

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 µg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

Different clinical presentation of community-onset bacteremia among neutropenic adults in the ED.

OBJECTIVES: To analyze the differences in clinical presentation and characteristics of community-onset bacteremia between neutropenic and nonneutropenic adults visiting the emergency department. METHODS: A case-control study with a ratio of 1:2 was conducted retrospectively over a 6-year period. Demographic characteristics, microorganisms, severity of illness, and clinical outcomes determined from medical records were analyzed. RESULTS: In total, 116 neutropenic adults (case patients) and 232 nonneutropenic adults (control patients) were examined. Significant differences in the source of bacteremia, susceptibility, and species of bacteremia-causing organisms between the case patients and control patients were observed by univariate analyses. Significantly more patients presenting with an initial syndrome of severe sepsis or septic shock at the emergency department, having high Pittsburgh bacteremia scores (≥4 points) or having severe comorbidities (McCabe classification), and high 28-day mortality rates were discovered in the case group, compared with the control group. Of note, Pseudomonas aeruginosa (32/137 [23.4%] vs 8/272 [2.9%], P < .001) was more often isolated from the case patients. In a further analysis using a multivariate regression to demonstrate the independent predictors of P aeruginosa infection, patients with neutropenia remained as an independent risk factors (odds ratio, 7.48; P < .001). CONCLUSIONS: This study demonstrated obvious differences of community-onset bacteremia in severity, the distribution of microorganisms, and susceptibility between neutropenic and nonneutropenic patients. Antipseudomonas therapy was empirically suggested for neutropenic patients with community-onset bacteremia and reducing the need for a glycopeptide.

Mediating effects of social support on depression and quality of life among patients with HIV infection in Taiwan.

Few empirical studies have evaluated the mediating effects of quality of life (QoL) among people living with HIV/AIDS (PLWHA). The purposes of this study were to identify the predictors of QoL and to test the mediating effects of social support on depression and QoL among patients enrolled in an HIV case-management program in Taiwan. A cross-sectional, descriptive correlation design collected data from 108 HIV-infected individuals. Individuals were assessed using the Beck Depression Inventory II, the short version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF), and the Multidimensional Scale of Perceived Social Support between September 2007 and April 2010. After adjusting for sociodemographic characteristics (including age, gender, and mode of transmission) and clinical information (including CD4 count and time since diagnosis with HIV), the study findings showed that QoL was significantly and positively correlated with both social support and the initiation of highly active antiretroviral therapy (HAART), and was negatively correlated with depression and time since diagnosis with HIV. The strongest predictors for QoL were depression followed by the initiation of HAART and social support, with an R(2) of 0.40. Social support partially mediated the relationship between depression and QoL. Health professionals should enhance HIV-infected individuals' social support to alleviate the level of depression and further increase the QoL among PLWHA.

Increased risk of Pneumocystis jirovecii colonization in rheumatoid arthritis patients on biologics and Janus kinase inhibitor.

BACKGROUND: The prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi). METHODS: A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization. RESULTS: One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization. CONCLUSION: RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o.

In vitro induction and selection of fluoroquinolone-resistant mutants in Elizabethkingia anophelis.

For 29 parent strains, recognized by pulsed-field gel electrophoresis, the MICs multiplied significantly in the ciprofloxacin group than levofloxacin group, following the first and third induction cycle. Ser83Arg in GyrA was the most common site of mutations. No mutation in ParC nor ParE was identified in the selected mutants.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study.

BACKGROUND: As limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6-10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. METHODS: A retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. RESULTS: Of 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0-76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01-0.63; P = 0.005). CONCLUSION: Short courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Optimizing SARS-CoV-2 vaccine responses in kidney transplant recipients: an urgent need.

Kidney transplant recipients (KTRs) have been identified as a population at increased risk for severe SARS-CoV-2 infection outcomes. This study focused on understanding the immune response of KTRs post-vaccination, specifically examining both serological and cellular responses to the SARS-CoV-2 vaccine. Thirteen individuals, including seven KTRs and six healthy donors, were evaluated for antibody levels and T cell responses post-vaccination. The study revealed that KTRs had significantly lower serological responses, including reduced anti-receptor binding domain (RBD) binding antibodies and neutralizing antibodies against the Wuhan, Delta, and Omicron BA.2 strains. Additionally, KTRs demonstrated weaker CD8 T cell cytotoxic responses and lower Th1 cytokine secretion, particularly IFN-γ, after stimulation with variant spike peptide pools. These findings highlight the compromised immunity in KTRs post-vaccination and underscore the need for tailored strategies to bolster immune responses in this vulnerable group. Further investigations are warranted into the mechanisms underlying reduced vaccine efficacy in KTRs and potential therapeutic interventions. IMPORTANCE: Some studies have revealed that KTRs had lower serological response against SARS-CoV-2 than healthy people. Nevertheless, limited studies investigate the cellular response against SARS-CoV-2 in KTRs receiving SARS-CoV-2 vaccines. Here, we found that KTRs have lower serological and cellular responses. Moreover, we found that KTRs had a significantly lower IFN-γ secretion than healthy individuals when their PBMCs were stimulated with SARS-CoV-2 spike peptide pools. Thus, our findings suggested that additional strategies are needed to enhance KTR immunity triggered by the vaccine.

Asymptomatic enteric pathogen carriage and its association with proton pump inhibitors use in men who have sex with men in Taiwan, 2019-2022.

OBJECTIVES: Currently recognized risk factors for sexually transmitted enteric infections (STEIs) among men who have sex with men (MSM) include oroanal sex, multiple sexual partners, and chemsex. This study aimed to investigate the prevalence of the asymptomatic carriage of enteric pathogens in men who have sex with men (MSM) and to identify the associated risk factors. METHODS: Questionnaires were completed by 375 MSM in Taiwan from December 2019 to November 2022. Fecal samples were analyzed by multiplex PCR to determine whether seven enteric pathogens, including Entamoeba histolytica, Giardia duodenalis, Shiga toxin-producing Escherichia coli, Cryptosporidium, Campylobacter, Salmonella, and Shigella species, were present. RESULTS: Among 375 fecal samples from asymptomatic MSM, 27 (7.2%) fecal samples tested positive for at least one enteric pathogen. The recent use of proton pump inhibitors (PPIs) was significantly associated with asymptomatic fecal carriage (22.2% vs. 2.0%, P < 0.001). G. duodenalis (2.1%, 8 cases), E. histolytica (1.6%, 6 cases), and Shigella species (1.3%, 5 cases) were commonly detected. Oroanal sex and PPI use were associated with the asymptomatic carriage of enteric pathogens. Specifically, Shigella, Salmonella, or Campylobacter carriage was significantly correlated with PPI use. In contrast, rectal gonorrhea was associated with multiple sexual partners and prior syphilis. CONCLUSIONS: Recent use of PPIs was associated with the asymptomatic carriage of enteric pathogens. Therefore, targeted education about the appropriate use of PPIs is necessary to mitigate the risk of STEIs among MSM.