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.

Surveillance of pathogenic yeasts in hospital environments in Taiwan in 2020.

BACKGROUND: A predominate azole-resistant Candida tropicalis clade 4 genotype causing candidemia has been detected in not only Taiwan but also China, Singapore, and Australia. It can also be detected on fruit surfaces. In addition to determining distribution and drug susceptibilities of pathogenic yeasts in environments of intensive care units of 25 hospitals in Taiwan, we would also like to investigate whether the azole-resistant C. tropicalis exists in Taiwan's hospital environment. METHODS: The swabs of hospital environments were collected from August to November in 2020 and were cultured for yeasts. The yeasts were identified by rDNA sequence and the antifungal susceptibilities of those isolates were determined by the broth microdilution method. RESULTS: The average yeast-culture rate of hospitals was 9.4% (217/2299). Sinks had the highest yeast-positive culture rate (32.7%), followed by bedside tables (28.9%), floors (26.0%), water-dispenser buttons (23.8%), and TV controller/touch panels (19.0%). Of 262 identified isolates, Candida parapsilosis was the most common species, accounting for 22.1%, followed by Filobasidium uniguttulatum (18.3%), Candida albicans (9.5%), C. tropicalis (8.0%), Candida glabrata (Nakaseomyces glabratus) (6.9%), and 30 other species (35.1%). Of the 21 C. tropicalis isolates from 11 units in 9 hospitals, 15 diploid sequence types (DSTs) were identified. The two DST506 fluconazole-resistant ones belonged to clade 4. CONCLUSION: We detected not only various pathogenic yeast species but also the predominant clade 4 genotype of azole-resistant C. tropicalis. Our findings highlight and re-emphasize the importance of regular cleaning and disinfection practices.

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.

PCR-Based Microarray Enhances Diagnosis of Culture-Negative Biopsied Tissue in Patients with Invasive Mold Infections: Real-World Experience in a Tertiary Medical Center.

A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.

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.

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.

A point-of-care electrochemical biosensor for the rapid and sensitive detection of biomarkers in murine models with LPS-induced sepsis.

Sepsis is a life-threatening condition, which is irreversible if diagnosis and intervention are delayed. The response of the immune cells towards an infection triggers widespread inflammation through the production of cytokines, which may result in multiple organ dysfunction and eventual death. Conventional detection techniques fail to provide a rapid diagnosis because of their limited sensitivity and tedious protocol. This study proposes a point-of-care (POC) electrochemical biosensor that overcomes the limitations of current biosensing technologies in the clinical setting by its integration with electrokinetics, enhancing the sensitivity to picogram level compared with the nanogram limit of current diagnostic technologies. This biosensor promotes the use of a microelectrode strip to address the limitations of conventional photolithographic fabrication methods. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and microRNA-155 (miR-155) were monitored in a lipopolysaccharide (LPS)-induced septic mouse model. The optimum target hybridization time in a high conductivity medium was observed to be 60 s leading to the completion of the whole operation within 5 min compared with the 4-h detection time of the traditional enzyme-linked immunosorbent assay (ELISA). The limit of detection (LOD) was calculated to be 0.84, 0.18, and 0.0014 pg mL-1, respectively. This novel sensor may have potential for the early diagnosis of sepsis in the clinical setting.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Tongue pressure during swallowing is an independent risk factor for aspiration pneumonia in middle-aged and older hospitalized patients: An observational study.

AIM: To evaluate oral frailty features present in hospitalized older patients with aspiration pneumonia. METHODS: We enrolled hospitalized patients aged ≥50 years and classified them into three groups: the community-acquired, aspiration, and non-community-acquired pneumonia groups. Oral frailty was defined as meeting three or more criteria from the following: choking, and decreased occlusal force, masticatory function, tongue-lip motor function, tongue pressure, and tongue pressure during swallowing. RESULTS: Of 168 patients enrolled, the incidence of aspiration pneumonia was 23.9% (17/71) in patients admitted with pneumonia as the primary diagnosis. The occlusal force and masticatory function were significantly poorer and tongue pressure and tongue pressure during swallowing were significantly lower in the aspiration pneumonia group than in the other two groups. A higher number of chronic comorbidities, poor oral health, and lower tongue pressure during swallowing were significantly associated with aspiration pneumonia. A tongue pressure during swallowing of <10.32 kPa might be a cutoff point for predicting the risk of aspiration pneumonia. CONCLUSIONS: Hospitalized patients aged ≥50 years with multiple comorbidities, poor oral hygiene, and oral frailty during swallowing are at a higher risk of developing aspiration pneumonia, especially when their tongue pressure during swallowing is <10.32 kPa. Aspiration pneumonia is a preventable disease. Healthcare professionals should incorporate tongue pressure measurements or other screening tools into routine clinical practice to facilitate the early detection of this condition and intervention. Geriatr Gerontol Int 2024; 24: 351-357.

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.

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.

Novel metal peroxide nanoboxes restrain Clostridioides difficile infection beyond the bactericidal and sporicidal activity.

Clostridioides difficile spores are considered as the major source responsible for the development of C. difficile infection (CDI), which is associated with an increased risk of death in patients and has become an important issue in infection control of nosocomial infections. Current treatment against CDI still relies on antibiotics, which also damage normal flora and increase the risk of CDI recurrence. Therefore, alternative therapies that are more effective against C. difficile bacteria and spores are urgently needed. Here, we designed an oxidation process using H2O2 containing PBS solution to generate Cl- and peroxide molecules that further process Ag and Au ions to form nanoboxes with Ag-Au peroxide coat covering Au shell and AgCl core (AgAu-based nanoboxes). The AgAu-based nanoboxes efficiently disrupted the membrane structure of bacteria/spores of C. difficile after 30-45 min exposure to the highly reactive Ag/Au peroxide surface of the nano structures. The Au-enclosed AgCl provided sustained suppression of the growth of 2 × 107 pathogenic Escherichia coli for up to 19 days. In a fecal bench ex vivo test and in vivo CDI murine model, biocompatibility and therapeutic efficacy of the AuAg nanoboxes to attenuate CDI was demonstrated by restoring the gut microbiota and colon mucosal structure. The treatment successfully rescued the CDI mice from death and prevented their recurrence mediated by vancomycin treatment. The significant outcomes indicated that the new peroxide-derived AgAu-based nanoboxes possess great potential for future translation into clinical application as a new alternative therapeutic strategy against CDI.

Rituximab, but not other biologics, impairs humoral immunity in patients with rheumatoid arthritis-a study using CoVariant protein arrays.

Objectives: RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA. The global spread and continuous variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate the monitoring of variant-specific humoral responses post-vaccination. The aim of this study was to investigate how different biologic treatments for vaccinated RA patients might affect their neutralizing antibodies against multiple SARS-CoV-2 variants. Methods: We recruited RA patients who had received three doses of conventional SARS-CoV-2 vaccines and were treated with various biologics, e.g. TNF inhibitor (etanercept), IL-6 inhibitor (tocilizumab), CTLA4-Ig (abatacept) or anti-CD20 (rituximab). Serum samples were used to profile the binding and neutralizing antibodies using our own SARS-CoV-2 variant (CoVariant) protein array, developed previously. Results: Compared with healthy controls, only RA therapy with rituximab showed a reduction in neutralizing antibodies capable of targeting spike proteins in SARS-CoV-2 wild-type and most variants. This reduction was not observed in binding antibodies against SARS-CoV-2 wild-type or its variants. Conclusion: After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious inhibition.

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.

Clinical impact of the combination of rapid species identification and antifungal stewardship intervention in adults with candidemia.

BACKGROUND: Candidemia is associated with a high mortality rate. This study aimed to evaluate the clinical impact of a diagnostic intervention and antifungal stewardship in adults with candidemia, including effectiveness in facilitating appropriate antifungals and improving patient outcomes. METHODS: A pre-post quasi-experimental study was conducted to analyze the impact of the integrated workflow of rapid species identification and antifungal stewardship intervention provided by infectious disease specialists for adults with candidemia at a medical center in southern Taiwan from March 1st, 2014 to February 29th, 2016. The primary endpoint was 30-day crude mortality, and secondary outcomes included the time to species identification, time to initial antifungal modification, and length of hospital stay. RESULTS: Total 303 patients with candidemia were included, including 152 adults in the pre-intervention period (Mar. 1st, 2014-Feb. 28th, 2015; control group) and 151 in the intervention period (Mar. 1st, 2015-Feb. 29th, 2016; case group). Demographic and clinical characteristics of patients in two groups were similar. The case group had a shorter time to species identification (72 vs. 96 h, P < 0.001) and earlier receipt of antifungals (47 vs. 59 h, P < 0.001) than the control group. Of note, the 30-day mortality rate (27.2% vs. 39.5%, P = 0.028) was lower and the hospital stay (43.5 vs. 46.0 days, P = 0.006) was shorter in the case group. CONCLUSION: Rapid diagnostic workflow and antifungal stewardship provided by infectious disease specialists can promote early initiation of antifungal therapy and improve outcome for adults with candidemia.

In-hospital mortality predictors among hospitalized adults and those with chronic kidney disease with dengue.

BACKGROUND: Accurately identifying risk factors that predict fatality in dengue is crucial for patient triage and clinical management. Our objective was to identify predictors of death associated with dengue and investigate the clinical characteristics and risk factors among patients with chronic kidney disease (CKD) who died from dengue. METHODS: A multicenter longitudinal observation study conducted from 2008 to 2019. RESULTS: A total of 1272 patients (113 who died and 1186 who recovered) diagnosed with dengue were included. Old age, CKD, and an elevated white blood cell count at hospital presentation were identified as independent predictors of in-hospital mortality among individuals infected with the dengue virus. In a subgroup analysis of 138 patients with CKD infected with dengue virus, 64 (46.3%) patients died, with 46 (33.3%) patients dying within 7 days after symptom onset. Among 64 fatal dengue patients with CKD, 34.4% were in stages 2 and 3 of kidney disease, 51.5% were in stages 4 and 5, and 14.1% had end stage renal disease as per the classification by Kidney Disease Improving Global Outcomes. Multivariate analysis revealed that initial altered consciousness, pulmonary edema, and leukocytosis during hospitalization were independently associated with in-hospital mortality in CKD patients infected with the dengue virus. Leukocytosis during hospitalization and severe hepatitis were independent risk factors for death within 7 days after dengue illness onset in CKD patients. CONCLUSIONS: This study offers valuable insights into predictors linked to fatality in dengue and reinforces the importance of optimizing patient triage to improve the quality of care.

Emergence and dissemination of multidrug-resistant Escherichia coli ST8346 coharboring blaNDM-5 and blaOXA-181 in Southern Taiwan, 2017-2021.

BACKGROUND: Enterobacterales carrying blaNDM represent an emerging challenge in treating infectious diseases. In this study, we aimed to investigate the characteristics of blaNDM-producing Enterobacterales from three hospitals in southern Taiwan. METHODS: Enterobacterales strains that were nonsusceptible to more than one carbapenem (ertapenem, meropenem, imipenem, or doripenem) were collected from hospitalized patients. Molecular typing for New Delhi metallo-ß-lactamase (NDM) and antibiotic susceptibility tests were performed, followed by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and plasmid analysis by PCR-based replicon typing. RESULTS: A total of 1311 carbapenem-nonsusceptible Enterobacterales were isolated from 2017 to 2021. blaNDM-encoding genes were detected in 108 isolates, with 53 (49.1%) harboring blaNDM-1 and 55 (50.9%) harboring blaNDM-5. The rate of blaNDM-1 detection among isolates decreased to 2% in 2021. However, the rate of E. coli harboring blaNDM-5 increased from 1% to 12% of total isolates during the study period. Of 47 NDM-5-positive E. coli isolates, 44 (93.6%) were ST8346 with high genetic relatedness. E. coli ST8346 isolates showed high-level resistance to both carbapenems and aminoglycosides. Most (38 out of 47, 80.9%) blaNDM-5-harboring E. coli isolates co-harbored blaOXA-181. We analyzed the regions harboring blaNDM-5 in E. coli ST8346 via PCR amplification. blaNDM-5 and blaOXA-181 were located on two separate plasmids, IncF and IncX3, respectively. CONCLUSION: The dissemination of E. coli ST8346 caused an increase in blaNDM-5 and blaOXA-181 co-harboring Enterobacterales in southern Taiwan, which show high-level resistance to both carbapenems and aminoglycosides. We identified a distinct IncF plasmid encoding blaNDM-5 that has the potential for rapid spread and needs further surveillance.