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Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Abstract Introduction Although antifungal supplementation reduces the fungal load in the corneal storage medium, consensus is lacking on the influence of dosing and temperature. The study aims to evaluate the impact of eye bank warming protocol and timing of antifungal supplements on efficacy in Optisol-GS and tissue. Methods Corneoscleral rims contaminated with Candida albicans (C. albicans) were incubated in Optisol-GS, either without antifungal agents or with the addition of amphotericin B or voriconazole at various concentrations (2 ×, 5 ×, 10 ×, and 20 × MIC), at different time points, and under various preservation temperatures (2–8 °C versus 2 h-room temperature exposure). Antifungal efficacy was evaluated by counting viable yeast colonies cultured from Optisol-GS samples. Tissue sterility was determined through direct tissue culture and histological examination of the contaminated rims after a 14-day incubation period. Results Room temperature exposure did not increase colony growth at the same multiple MIC of antifungal agents. Although antifungal addition reduced C. albicans growth in a concentration-dependent manner, yeast growth was still observed in all Optisol-GS samples with a single supplementation after a 14-day incubation. Only groups with additional antifungal supplementation on either day 2 or day 6 showed a 99% or greater reduction of C. albicans growth in Optisol-GS samples and yielded negative results in direct tissue culture. Conclusions The eye bank warming protocol did not compromise antifungal efficacy. To sustain the required concentration and effectively reduce C. albicans growth in Optisol-GS and contaminated tissue, additional antifungal supplementation on either day 2 or day 6 was necessary during a 2-week preservation period.

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians’ decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97–1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94–1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12–1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02–1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01–1.98). Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.

Background: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. Methods: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. Results: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64–15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04–5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45–19.15), and receiving

Candida tropicalis-a prevalent gut commensal fungus in healthy individuals – contributes to intestinal health and disease. However, how commensal C. tropicalis influences intestinal homeostasis and barrier function is poorly understood. Here, we demonstrated that the reference strain of C. tropicalis (MYA-3404) ameliorated intestinal inflammation in murine models of chemically induced colitis and bacterial infection. Intestinal colonization of C. tropicalis robustly upregulated the expression of IL-17A and IL-22 to increase barrier function and promote proliferation of intestinal epithelial cells in the mouse colon. Metabolomics analysis of fecal samples from mice colonized with C. tropicalis revealed alterations in vitamin B3 metabolism, promoting conversion of nicotinamide to nicotinic acid. Although nicotinamide worsened colitis, treatment with nicotinic acid alleviated disease symptoms and enhanced epithelial proliferation and Th17 cell differentiation. Oral gavage of C. tropicalis mitigated nicotinamide-induced intestinal dysfunction in experimental colitis. Blockade of nicotinic acid production with nicotinamidase inhibitors lowered the protective effects against colitis in mice treated with C. tropicalis. Notably, a clinical C. tropicalis strain isolated from patients with candidemia lacked the protective effects against murine colitis observed with the reference strain. Together, our results highlight a novel role for C. tropicalis in resolving intestinal inflammation through the modulation of vitamin B3 metabolism.

Background: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). Material and methods: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. Results: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017–2019, but no further increase during the pandemic period in 2020–2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. Conclusion: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

Background: The role of environmental contamination in COVID-19 transmission within hospitals is still of interest due to the significant impact of outbreaks globally. However, there is a scarcity of data regarding the utilization of environmental sampling for informing infection control measures during SARS-CoV-2 outbreaks. Methods: This retrospective study analyzed incident event investigations conducted at a single center from May 1, 2021, to August 31, 2021. Investigations were initiated following the identification of a COVID-19 confirmed case (referred to as the index case) who had stayed in a hospital area outside the dedicated COVID-19 ward/bed and without specific COVID-19 precautions. Measures to prevent intra-hospital spread included contact tracing, adjusted testing policies, isolation of confirmed cases, quarantine of close contacts, environmental disinfection, and PCR testing of environmental samples. Results: Among the 18 incident events investigated, the index case was a healthcare personnel in 8 events, a patient in 8 events, and a caregiver in 2 events. The median number of confirmed COVID-19 cases within 14 days was 13 (IQR, 7–31) for events with SARS-CoV-2 RNA detected on environmental surfaces, compared to only one (IQR, 1–1.5) for events without surface contamination (P = 0.04). Environmental contamination was independently associated with a higher number of COVID-19 cases (P

Background: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. Methods: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. Results: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. Conclusion: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Background: Patients recovering from COVID-19 may need vaccination against SARS-CoV-2 because acquired immunity from primary infection may wane, given the emergence of new SARS-CoV-2 variants. Understanding the trends of anti-spike IgG and neutralizing antibody titers in patients recovering from COVID-19 may inform the decision made on the appropriate interval between recovery and vaccination. Methods: Participants aged 20 years or older and diagnosed with COVID-19 between January and December, 2020 were enrolled. Serum specimens were collected every three months from 10 days to 12 months after the onset of symptom for determinations of anti-spike IgG and neutralizing antibody titers against SARS-CoV-2 Wuhan strain with D614G mutation, alpha, gamma and delta variants. Results: Of 19 participants, we found a decreasing trend of geometric mean titers of anti-spike IgG from 560.9 to 217 and 92 BAU/mL after a 4-month and a 7-month follow-up, respectively. The anti-spike IgG titers declined more quickly in the ten participants with severe or critical disease than the nine participants with only mild to moderate disease between one month and seven months after SARS-CoV-2 infection (−8.49 vs - 2.34-fold, p

Background: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. Methods: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). Results: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan.

Candida albicans is a commensal microorganism in the human gut but occasionally causes invasive C. albicans infection (ICA), especially in immunocompromised individuals. Early initiation of antifungal therapy is associated with reduced mortality of ICA, but rapid diagnosis remains a challenge. The ICA-associated changes in the gut microbiota can be used as diagnostic and therapeutic targets but have been poorly investigated. In this study, we utilized an immunodeficient Rag2γc (Rag2-/-il2γc-/-) mouse model to investigate the gut microbiota alterations caused by C. albicans throughout its cycle, from its introduction into the gastrointestinal tract to invasion, in the absence of antibiotics. We observed a significant increase in the abundance of Firmicutes, particularly Lachnospiraceae and Ruminococcaceae, as well as a significant decrease in the abundance of Candidatus Arthromitus in mice exposed to either the wild-type SC5314 strain or the filamentation-defective mutant (cph1/cph1 efg1/efg1) HLC54 strain of C. albicans. However, only the SC5314-infected mice developed ICA. A linear discriminate analysis of the temporal changes in the gut bacterial composition revealed Bacteroides vulgatus as a discriminative biomarker associated with SC5314-infected mice with ICA. Additionally, a positive correlation between the B. vulgatus abundance and fungal load was found, and the negative correlation between the Candidatus Arthromitus abundance and fungal load after exposure to C. albicans suggested that C. albicans might affect the differentiation of intestinal Th17 cells. Our findings reveal the influence of pathogenic C. albicans on the gut microbiota and identify the abundance of B. vulgatus as a microbiota signature associated with ICA in an immunodeficient mouse model.

Background/Purpose: Healthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan. Methods: Sequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection. Results: Totally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P

Background: New tetracycline derivatives exhibit broad-spectrum antimicrobial activities. This study aimed to assess the in vitro activity of eravacycline against common Enterobacterales. Methods: Clinical Enterobacterales isolates were collected between 2017 and 2021. The minimum inhibitory concentration (MIC) was determined using a broth microdilution test. Results: We identified Klebsiella pneumoniae (n = 300), Escherichia coli (n = 300), Klebsiella oxytoca (n = 100), Enterobacter cloacae complex (n = 100), Citrobacter freundii (n = 100), and Proteus mirabilis (n = 100). All P. mirabilis strains were resistant to eravacycline. Excluding P. mirabilis, the susceptibility rates to eravacycline, omadacycline, and tigecycline were 75.2%, 66.9%, and 73%, respectively. The MIC50 and MIC90 (mg/L) of eravacycline were 0.5 and 4 for K. pneumoniae, 0.5 and 1 for E. coli, 0.5 and 1 for K. oxytoca, 0.5 and 2 for E. cloacae complex, and 0.25 and 1 for C. freundii. In cefotaxime non-susceptible and meropenem susceptible Enterobacterales, excluding P. mirabilis, the susceptibility rates of eravacycline, omadacycline, and tigecycline were 69.7%, 57.1%, and 66.2%. We found decreased susceptibility rates of three new tetracycline derivatives against meropenem non-susceptible Enterobacterales (eravacycline: 47.1%, omadacycline: 39.4%, and tigecycline: 39.4%). Eravacycline showed a high susceptibility rate against cefotaxime non-susceptible and meropenem susceptible K. oxytoca (100%), C. freundii (93.2%), E. coli (85.9%), and meropenem non-susceptible E. coli (100%). Conclusion: This study provides the MIC and susceptibility rate of eravacycline for common Enterobacterales. Eravacycline could be a therapeutic choice for cefotaxime non-susceptible or meropenem non-susceptible Enterobacterales, especially K. oxytoca, C. freundii, and E. coli.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Objectives: We analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Methods: We conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. Results: A total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height 12.2 mg/l was a risk factor for thrombocytopenia. Conclusion: The LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

Amphotericin B and itraconazole are the primary agents for treating histoplasmosis. Newer azoles are alternatives for patients refractory to or intolerant of standard therapy. We report an 83-year-old woman with rheumatoid arthritis complicated with pleuropulmonary histoplasmosis who responded to liposomal amphotericin B, but progressed under voriconazole and posaconazole maintenance therapy.

Abstract Introduction High-dose daptomycin-based combinations are recommended for vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Preclinical data have shown a synergistic effect of daptomycin/fosfomycin combinations against VRE. However, clinical studies comparing daptomycin monotherapy with daptomycin/fosfomycin combinations are unavailable. Methods An observational study of VRE-BSI was performed between 2010–2021 on patients receiving daptomycin monotherapy (≥ 8 mg/kg) or daptomycin combined with intravenous fosfomycin. Patients treated with concomitant β-lactam combinations were excluded. The primary outcome was in-hospital mortality. Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW) analyses. Results Among 224 patients, 176 received daptomycin monotherapy, and 48 received fosfomycin combinations. The median daptomycin and fosfomycin doses were 9.8 mg/kg and 12 g/day, respectively. In-hospital mortality was 77.3% and 47.9% in the daptomycin monotherapy and fosfomycin combination groups (P

Background: The treatment options for vancomycin-resistant Enterococcus (VRE) are limited. A combination of daptomycin (DAP) and β-lactam (BL) has been suggested; however clinical studies supporting this are lacking. Methods: Patients with VR E. faecium bacteremia who received ≥ 8 mg/kg daptomycin for ≥ 72 h and initiated ≤ 5 days of culture collection between 2010 and 2021 were included. DAP+BL was defined as receiving BL for ≥ 24 h and within 24 h of DAP initiation. The primary endpoint was a composite clinical success (neither 14-day mortality, microbiological failure, nor change in the anti-VRE regimen). Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW). Results: A total of 430 patients were enrolled (DAP, n = 45; DAP+BL, n = 385). Clinical success was achieved in 19 (42.2%) patients in the DAP group and 244 (63.4%) in the DAP+BL group [adjusted odds ratio, 3.19; 95% confidence interval (CI) 1.61–6.33; P = 0.001]. Marginal analysis showed that the efficacy of DAP+BL was particularly significant with DAP dose ≥ 9 mg/kg and DAP minimum inhibitory concentration (MIC) ≥ 2 mg/L. With the balance of AIPW, standardized mean clinical success rates for DAP and DAP+BL 37.3% and 63.5%, respectively. The difference between DAP+BL and DAP was of 26.2% in favor of DAP+BL (95% CI, 10.0–42.3%; P = 0.001). Conclusions: DAP+BL was associated with a significantly higher rate of compositive clinical success than DAP for treatment of VR E. faecium bacteremia. The study suggested BL in combination with high-dose DAP for VR E. faecium bacteremia treatment, especially when VRE showed a high DAP MIC.

Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn’t. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P

Background: The surgical outcome for primary pulmonary cryptococcosis remains unclear. In this study, we investigated the clinical characteristics, treatment, and outcomes of video-assisted thoracoscopic surgery (VATS) for primary pulmonary cryptococcosis. Methods: We retrospectively reviewed the medical records of 49 patients with confirmed pulmonary cryptococcosis who underwent VATS for pulmonary nodules at the National Taiwan University Hospital between May 2013 and March 2019. Serum cryptococcal antigen (CryAg)-positive and CryAg-negative patients were compared. Results: The diagnosis of pulmonary cryptococcosis was confirmed using histopathology or tissue swab culture. The mean age of the patients was 56.0 ± 12.2 years, and 27 patients (55.1%) were male. Most patients were asymptomatic (67.3%) and admitted following the detection of pulmonary lesions on a computed tomography scan of the chest. A greater proportion of patients in the CryAg-positive group (62.5%) underwent lobectomy compared with those in the CryAg-negative group (7.3%, P

Background/Purpose: Invasive candidiasis is a severe infectious disease that could lead to mortality in critically ill children. Methods: We collected data regarding demographics, underlying diseases, predisposing factors, outcomes for pediatric patients with candidemia at a medical centre in Taiwan from 2011 to 2017. Results: Fifty-eight patients with 60 candidemia episodes were diagnosed. The 3 most common species were Candida albicans (42%), Candida parapsilosis (25%) and Candida tropicalis (23%). C. parapsilosis predominantly infected infants and neonates (median age: 0.8 years, range: 0.1–14.5). Cases with C. tropicalis had significantly higher rates of multidrug resistance (p = 0.011) and disseminated candidiasis (p = 0.025) compared with other cases. The all-cause mortality rate was 43%, and the candidemia-related mortality rate was 29%. Pediatric sequential organ failure assessment score >8 [adjusted odds ratio (aOR) 66.2, 95% CI 4.03–1088.5] and posaconazole resistance (aOR 33.57, 95% CI 1.61–700.3) were the most significant risk factors associated with candidemia-related mortality, whereas treatment with effective antifungal agents within 48 h (aOR 0.07, 95% CI 0.01–0.9) was the only significant protective factor. Conclusion: Candidemia-related mortality was related to azole resistance; therefore, empirical therapy with echinocandin or amphotericin B is recommended pending species and susceptibility results.

Objectives: We aimed to determine the synergistic effects of ceftaroline (CPT) in combination with daptomycin (DAP), vancomycin (VAN), or linezolid (LNZ) against various methicillin-resistant Staphylococcus aureus (MRSA) strains. Methods: MRSA strains randomly selected from 2014 to 2018 were studied. Checkerboard titration and in vitro time-kill analyses were used to determine the synergistic activities of the antibiotic combinations. Results: A total of 10 genetically distinct MRSA strains were included in this study. The checkerboard titration analysis revealed that the CPT-DAP, CPT-VAN, and CPT-LNZ combinations had a synergistic effect against 30%, 10%, and 10% of the selected MRSA strains, respectively. Using time-kill analysis, we showed that CPT-DAP exhibited a significant synergistic and sustained bactericidal effect against both DAP-susceptible (Δ colony-forming units/ml, –5.79; P = 0.0495) and DAP-resistant (Δ colony-forming units/ml, –6.40; P = 0.0463) MRSA strains at a concentration of 0.5 × the minimum inhibitory concentration of CPT plus 0.5 × the minimum inhibitory concentration of DAP. No synergistic bactericidal effects were observed for the CPT-VAN and CPT-LNZ combinations against the selected strains. Conclusion: The CPT-DAP combination showed better synergistic activity than the CPT-VAN and CPT-LNZ combinations against the enrolled MRSA strains. DAP, rather than VAN or LNZ, might be a better choice for CPT combination in the treatment of MRSA infections.

Background: In many patients, low-dose computed tomography (CT) screening for lung cancer reveals asymptomatic pulmonary nodules. Lung resection surgery may be indicated in these patients; however, distinguishing malignancies from benign lesions preoperatively can be challenging. Methods: From 2013 to 2018, 4181 patients undergoing surgery for pulmonary nodules were reviewed at National Taiwan University Hospital, and 837 were diagnosed with benign pathologies. Only patients with pathological diagnosis as caseating granulomatous inflammation were included, sixty-nine patients were then analyzed for preoperative clinical and imaging characteristics, surgical methods and complications, pathogens, medical treatment and outcomes. Mycobacterial evidence was obtained from the culture of respiratory or surgical specimen. Results: Overall, 68% of the patients were asymptomatic before surgery. More than half of the nodules were in the upper lobes, and all patients underwent video-assisted thoracoscopic surgery (VATS). Some patients (14.5%) developed grade I complications, and the mean postoperative hospital stay was 4 days. The final pathology reports of 20% benign entities postoperatively, and caseating granulomatous inflammation accounted for a significant part. MTB and NTM were cultured from one-fourth of the patients respectively. All patients with confirmed MTB infection received antimycobacterial treatment, while the medical treatment in NTM-infected patients was decided by the infectious disease specialists. The mean follow-up period was 736 days, and no recurrence was found. Conclusion: Lung resection surgery is an aggressive but safe and feasible method for diagnosing MTB- or NTM-associated pulmonary nodules, and, potentially, an effective therapeutic tool for patients with undiagnosed MTB- or NTM-associated pulmonary nodules.

Purpose: Precise subspeciation of Mycobacterium abscessus complex (MAB) is crucial for predicting antibiotic susceptibilities and patient outcomes. However, routine clinical microbiology laboratories have limited diagnostic tools for the differentiation of the subspecies. Thus, we investigated the predictors for MAB subspecies to actuate rapid differentiation and the optimal treatment plans. Methods: We retrospectively identified stored clinical isolates of MAB and reviewed patient medical records to compare clinical characteristics, sites of infection, and outcomes among patients infected with M. abscessus subsp. abscessus (M. abscessus) and M. abscessus subsp. massiliense (M. massiliense). MAB subspecies were characterised by multilocus sequence analysis with 3-locus sequence (hsp65, rpoB, and secA1) and pulsed-field gel electrophoresis. Results: After outbreak and duplicated cases were excluded, 56 and 36 patients with infection caused by M. abscessus and M. massiliense, respectively, were included in the analysis. Patients with either cardiovascular disease or risk factors for cardiovascular disease (male gender and age ≥55 years) were 4.5 times more likely to harbour M. abscessus (P = 0.002), whereas M. massiliense was 4.8 times more frequently recovered from cutaneous and surgical wounds (P = 0.04). Conclusion: Distinct host and organ specificity were observed among patients infected with M. abscessus and those with M. massiliense. These differences may provide clinically significant clues to optimise treatment strategies.

Background: Healthcare personnel (HCP) at the front line of care are exposed to occupational hazards that place them at risk for infection, which then endanger patient safety and compromise the capability of the healthcare workforce. As of March 8, 2021 more than 420,170 HCP in US had been infected with SARS CoV-2 with 1388 deaths. In two Taiwan hospitals COVID-19 outbreaks involved HCP and resulted in shutdown of service. This report describes our prospective health surveillance of the HCP and COVID-19 containment measures in a teaching hospital in Taiwan during Jan. 1 through June 30, 2020. Methods: We prospectively monitored incidents, defined as an HCP with the predefined symptoms, reported by HCP through the web-based system. HCP were managed based on an algorithm that included SARS CoV-2 RNA PCR testing. Infection prevention and control policy/practice were reviewed. Results: This hospital took care of 17 confirmed COVID-19 cases during the study period and the first Case was admitted on January 23, 2020. Among the 14,210 HCP, there were 367 incident events. Of 283 HCP tested for SARS CoV-2, 179 had predefined symptoms. These included 10 HCP who met the national case definition for COVID-19 infection and 169 based on Extended COVID-19 Community Screening program. The other 104 asymptomatic HCP were tested based on hospital policy. All of them had tested negative. Conclusion: We attribute our success in preventing COVID-19 infections among HCP to rapid, proactive, decisive, integrated national and institutional response in the early stages of the epidemic

Background/Purpose: Accurate identification of Candida species is increasingly important in the era of emergence of Candida auris. We aimed to compare the identification performance of two matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems (Vitek MS and Bruker biotyper MS) and an oligonucleotide array for uncommon blood yeast isolates and demonstrate the susceptibilities among those isolates. Method: Candida species isolates from blood culture other than Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, and Candida krusei identified by biochemical methods were collected from multiple hospitals and further identified by an oligonucleotide array based on the internal transcribed spacer-1 (ITS-1) and ITS-2 sequences of the rRNA genes, Vitek MS and Bruker biotyper MS. The minimal inhibitory concentrations (MICs) of these clinical isolates were determined by the Sensititre YeastOne (SYO) system. Results: Among 136 isolates, Candida guilliermondii was most common (52, 38.2%), followed by C. lusitaniae (13, 9.6%) and C. haemulonii (12, 8.8%). The oligonucleotide array, Vitek MS and Bruker biotyper MS correctly identified 89.7% (122), 90.4% (123), and 92.6% (126) of these isolates, respectively. Elevated minimal inhibitory concentrations (MICs) of fluconazole were observed for C. haemulonii (MIC90: 256 mg/L), and C. guilliermondii (MIC90: 16 mg/L) with 28.4% of uncommon Candida isolates with MIC ≧ 8 mg/L. Conclusions: For uncommon Candida species, the unmet need for current databases of two commercial MALDI-TOF MS systems is highlighted, and the oligonucleotide array may serve as a supplement.

Objectives: Central-line–associated bloodstream infection (CLABSI) has been the leading cause of healthcare-associated infections (HAIs) in the intensive care unit (ICU) setting. Previous studies have shown that a care bundle is effective in reducing CLABSI rates; however, the data on long-term sustainability and cost savings of bundled care are limited. Methods: From January 2011 to December 2020, a prospective surveillance was performed to monitor CLABSI at a university hospital in northern Taiwan. To reduce the CLABSI rate, a hospital-wide bundled care program for CLABSI prevention was implemented in 2013. We evaluated the long-term effect of the care bundle on CLABSI incidence and length of stay in the ICU. Results: During the study period, the overall CLABSI incidence decreased from 8.22 per 1,000 catheter days before the care bundle was implemented to 6.33 per 1,000 catheter days in 2020 (P for trend

We presented the clinical course and immune responses of a well-controlled HIV-positive patient with COVID-19. The clinical presentation and antibody production to SARS-CoV-2 were similar to other COVID-19 patients without HIV infection. Neutralizing antibody reached a plateau from 26th to 47th day onset but decreased on 157th day after symptoms.

Background: In Taiwan, carbapenem-resistant Klebsiella pneumoniae (CRKP) now became a leading cause of difficult-to-treat healthcare-associated infection, for which there are a lack of recent hospital epidemiological studies on risk factors, mortality, and antimicrobial susceptibility. Methods: We prospectively enrolled patients with healthcare-associated CRKP monomicrobial bloodstream infection (mBSI) and matched patients with carbapenem susceptible K. pneumoniae (CSKP) mBSI at National Taiwan University Hospital (Taipei, Taiwan) from October 2017 through December 2019 in a 1:2 ratio. Multivariable logistic regression and Kaplan–Meier analyses were applied to identify factors associated with CRKP mBSI and to compare the 14-day survival curves, respectively. We detected the presence of blaKPC and blaNDM gene among the included CRKP strains, and performed antimicrobial susceptibility testing (including susceptibility to colistin, aminoglycoside, tigecycline, and ceftazidime/avibactam). Results: A total of 36 CRKP cases and 72 CSKP controls were enrolled. Patients with CRKP mBSI were more likely to have liver cirrhosis (adjusted odds ratio [aOR], 5.61; P = 0.024), length of hospital stay over the previous 14 days (aOR, 1.23; P = 0.001) and prior use of carbapenems in the previous 14 days (aOR, 6.07; P = 0.004) than patients with CSKP mBSI. The 14-day survival was significantly worse for patients with CRKP mBSI than those with CSKP mBSI (all CRKP cases: 50.0% vs. 87.5%; P

Background/purpose: Invasive Trichosporon infections are emerging, but association of different therapeutic management of Trichosporon fungemia and clinical outcomes were rarely reported. This study investigates the epidemiology, species distribution and genotypes of trichosporonosis in Taiwan, and identified the predictors of clinical outcomes in patients with Trichosporon fungemia. Methods: Strains collected from four medical centers in Taiwan, during 2010–2018. Species identification was confirmed by sequencing of IGS1 region, and antifungal susceptibility was performed using Sensititre YeastOne panel. Results: Among 115 isolates, Trichosporon asahii was the leading species (73.0%), followed by Trichosporon dermatis (11.3%), Trichosporon faecales (6.1%), and Trichosporon montevideense (5.2%). Of the 84 T. asahii isolates, genotype 1 was the predominant (41.7%). High fluconazole minimal inhibitory concentration (MICs,≧8 μg/mL) were observed for 70.2% T. asahii isolates and 16.1% non-asahii Trichosporon isolates. Posaconazole and voriconazole possess the most potent antifungal activity against all Trichosporon isolates, with geometric mean values of 0.251 μg/mL and 0.111 μg/mL, respectively. Fifty-three isolates collected from blood cultures, and 42 patients with fungemia enrolled for the Kaplan–Meier plot which revealed that voriconazole treatment had a significantly better survival rate compared with those without (p = 0.042). In multivariate analysis, source control (odds ratio [OR]: 0.13 95%CI [confidence interval]: 0.02–0.83, p = 0.031) and voriconazole use (OR: 0.11 95%CI: 0.02–0.74, p = 0.023) are independent predictors of 14-day mortality. Conclusion: This is the largest series of Trichosporon fungemia up till the present moment. Voriconazole therapy and source control play important roles in 14-day mortality.

ABSTRACT A high daptomycin dose has been suggested for treating vancomycin-resistant Enterococcus faecium (VREf) infections. However, even a 12 mg/kg daptomycin dose might be insufficient for treating VREf with high daptomycin minimum inhibitory concentrations (MICs). Additionally, animal pharmacodynamic and infection models to confirm the efficacy of 12 mg/kg daptomycin are lacking. Male Wistar rats were used for pharmacokinetic profiling and for the development of an infective endocarditis (IE) model. Daptomycin-susceptible dose-dependent VREf (DSE) (MIC of 0.5 mg/L) and daptomycin nonsusceptible VREf (DNSE) (MIC of 8 mg/L) were used for the IE models. The bacterial load of vegetation was the primary outcome and was evaluated after 3 days of daptomycin treatment. Daptomycin administered subcutaneously (s.c.) at 45 and 90 mg/kg, which corresponded to maximum serum concentrations (Cmax) of 122.6 mg/L and 178.5 mg/L, respectively, was equivalent to doses of 8 mg/kg and 12 mg/kg, respectively, in humans. The Cmax/MIC value was correlated with the bacterial load of vegetation after treatment (r = −0.88, P < 0.001). The 90 mg/kg s.c. group showed a significantly lower bacterial load of vegetation (log10 CFU/g) than the 45 mg/kg s.c. group against DSE (0 versus 4.75, P < 0.001) and DNSE (5.12 versus 6.98, P = 0.002). The 90 mg/kg s.c. group did not sterilize the vegetation against DNSE. Although the human equivalent dose of 12 mg/kg daptomycin was more effective than the smaller dose in reducing the bacterial load in DSE and DNSE IE, the dose could not sterilize the vegetation during a DNSE treatment. Further treatment strategies by which to manage severe VREf infections, especially at high daptomycin MICs, are urgently needed. IMPORTANCE Using a rat IE model with pharmacokinetic analysis, the treatment response of VREf IE was found to be daptomycin dose-dependent, presented as Cmax/MIC or as the 24 h area under the concentration-time curve (AUC0–24)/MIC. Daptomycin 90 mg/kg s.c. significantly reduced the bacterial load against DSE and DNSE. It also showed significant activity against DSE and DNSE, compared to 45 mg/kg s.c. Although daptomycin 90 mg/kg can eradicate the bacterial load after 3 days of treatment against DSE, eradication cannot be achieved with 90 mg/kg daptomycin against DNSE.

Background: Healthcare workers (HCWs) are at the frontline during the pandemic of COVID-19 globally. According to the WHO situation report at April 17, there were 22, 073 HCWs contracted the infection. Whether the infection control policy and practice in the hospital setting can protect the HCWs is an important issue. Methods: We performed a cross-sectional serology study in a tertiary care hospital in Taiwan to explore the sero-prevalence rate among HCWs. The participants are enrolled on a voluntary basis. A structured questionnaire was collected to gather the epidemiology character and risk factors for potential exposure. ELISA tests as Architect SARS-CoV-2 IgG (Abbott) and Elecsys Anti-SARS-CoV-2 assay (Roche) were used to detect antibody responses. If any of the tests was positive, a western blot assay was used for confirmation. Results: There were 194 HCWs participated during July 1 to Aug. 31, 2020. The mean age was 36.3 ± 10.4. More than half of the participants had possible hospital associated risk for COVID-19 exposure (110/192, 57.3%) and 64 had possible community risk for COVID-19 exposure (64/194, 33.0%). There was only one participant had positive test by Architect IgG test and confirmed to be negative for seasonal coronavirus and SARS-CoV-2 antibody. (Mikrogen Diagnostik, Germany). Conclusion: The cross-sectional serology study in a tertiary care hospital in Taiwan revealed no HCWs had positive serology response to SARS-CoV-2. We believe that the infection control policy and practice in the hospital and in the community are both important to prevent the disease transmission.

Because of the high incidence of cytomegalovirus (CMV) seropositivity in the population, CMV infection is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Taiwan. Here we propose a CMV management strategy for patients undergoing allo-HSCT from the Taiwanese perspective, which focuses on the epidemiology, diagnosis, monitoring, prophylaxis, and treatment of CMV infection after allo-HSCT. In terms of CMV monitoring, weekly CMV monitoring with the COBAS® AmpliPrep system is the standard approach because the pp65 CMV antigenemia assay has a lower sensitivity than CMV monitoring with the COBAS® AmpliPrep system. However, pp65 CMV antigenemia assay has a better correlation with clinical symptoms in immunocompromised patients. A 14-week prophylactic course of letermovir is recommended for allo-HSCT recipients in Taiwan, especially for recipients of hematopoietic stem cells from mismatched unrelated and haploidentical donors. Preemptive ganciclovir therapy should be initiated when the CMV viral load exceeds 1000 copies/mL, and should not be discontinued until CMV DNA is no longer detected in the blood. For allo-HSCT recipients who have CMV-related diseases, ganciclovir with or without CMV-specific intravenous immunoglobulin is the standard of care. The limited availability of foscarnet, an alternative for patients who are not responsive to or cannot tolerate ganciclovir, is a crucial issue in Taiwan. For pediatric allo-HSCT recipients, more data are needed to propose a CMV management recommendation.

Until now, there are no approved treatment against COVID-19. Hydroxychloroquine (HCQ) was hypothesized to be active against SARS-CoV2 via antiviral and anti-inflammatory effect; however, HCQ for COVID-19 in clinical use remained debating. In this preliminary report, we presented six patients with mild to moderate COVID-19. They were treated with HCQ for 14 days from the day of COVID-19 diagnosis. Serial viral load from respiratory specimens were performed every other day. Cytokine profile was checked before HCQ initiation and on the 14th day of HCQ treatment. All patients receiving HCQ completed 14-day course without complication. Among the six patients, the mean duration from symptom onset to last detectable viral load was 34 ± 12 days, which was similar to those without specific treatment in previous reports. Low level of interferon-gamma was noted in all patients of different stage of infection and three patients had elevation of IL-17 level. Prolonged virus shedding is still observed regardless HCQ. The impact of HCQ on cytokine kinetics remained unclear; however, IL-17 could be an inflammatory marker for disease status monitor and a potential therapeutic target.

Background: Candidemia caused by uncommon Candida species is increasing and misidentification may compromise optimal antifungal therapy. This multicenter study aimed to evaluate the accuracy of species-level identification of uncommon Candida. Methods: Uncommon causative species of candidemia identified in routine laboratories using CHROMagar, API-32C and VITEK-2 Yeast ID system were collected from July 2011 to June 2014. These isolates were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system and sequencing of the internal transcribed spacer and 28S rRNA gene. Susceptibility of the isolates was determined. Results: Of 85 isolates evaluated, Candida guilliermondii (n = 36) was the most common, followed by Candid sake (n = 7) and Candida famata (n = 4). Using DNA-sequencing analysis as standard, none of C. sake and C. famata was correct, while VITEK MS correctly identified 10 of the 11 isolates. With the exclusion of one unspecified Candida by DNA-sequencing methods, the accuracy of conventional methods and VITEK MS was 64.3% and 86.9%, respectively (p = 0.001). Eight isolates were confirmed to be yeasts other than Candida. Compared with other Candida species, C. guilliermondii showed elevated minimal inhibitory concentration of echinocandins. Conclusion: Misidentification of uncommon Candida species was common using the conventional methods, especially for C. sake and C. famata. MALDI-TOF MS assisted by DNA-sequencing methods should be considered.

Background/Purpose: Vancomycin-resistant Enterococcus (VRE), a multidrug-resistant, difficult-to-treat pathogen of healthcare-associated infections (HAIs), is now endemic at many intensive care units (ICUs). Chlorhexidine (CHG) bathing is a simple and highly effective intervention to decrease VRE acquisition, but its effect on VRE-HAIs has not been assessed in prospective studies at ICUs. Methods: This is a cluster quasi-experimental controlled study. Under active VRE surveillance and contact isolation of all identified VRE carriers, four ICUs were assigned to provide 2% CHG bathing for all patients on a daily basis (CHG group) during the intervention period, while another four ICUs were assigned to provide standard care without CHG bathing for all patients (standard care group) during the same period. Results: The CHG group (n = 1501) had a 62% lower crude incidence of VRE-HAIs during the intervention period, compared with the baseline period (1.0 vs. 2.6 per thousand patient-days, P = 0.009), while VRE-HAIs incidence did not change in standard care group (n = 3299) (1.1 vs. 0.5 per thousand patient-days, P = 0.139). In multivariable analyses, CHG bathing was independently associated with a 70% lower risk of VRE-HAIs (adjusted odds ratio [OR] 0.3, 95% confidence interval [CI], 0.2 to 0.7, P = 0.006). In contrast, standard care during the same period had no effect on the risk of VRE-HAIs (adjusted OR 1.8, 95% CI: 0.7 to 4.7, P = 0.259). Conclusion: CHG bathing is a highly effective approach to prevent VRE-HAIs at ICUs, in the context of active VRE surveillance with contact isolation.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a newly identified pathogen causing the coronavirus disease 2019 (COVID‐19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti‐inflammatory drug, has been shown to inhibit SARS‐CoV‐2 infection in vitro and tested in clinical studies. However, achievement of lung concentrations predicted to have in vivo antiviral efficacy might not be possible with the currently proposed oral dosing regimens. Further, high cumulative doses of HCQ raise concerns of systemic toxicity, including cardiotoxicity. Here, we describe a preclinical study to investigate the pharmacokinetics (PKs) of a novel formulation of liposomal HCQ administered by intratracheal (IT) instillation in Sprague‐Dawley rats. Compared with unformulated HCQ administered intravenously, liposomal HCQ showed higher (~ 30‐fold) lung exposure, longer (~ 2.5‐fold) half‐life in lungs, but lower blood exposure with ~ 20% of peak plasma concentration (Cmax) and 74% of area under the curve from 0 to 72 hours (AUC0–72) and lower heart exposure with 23% of Cmax and 58% of AUC0–24 (normalized for dose). Similar results were observed relative to IT administration of unformulated HCQ. These PKs result in an animal model that demonstrated the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID‐19.

Sequence type (ST) 8 has not been a common methicillin-resistant Staphylococcus aureus (MRSA) clone in Asia until recently. We aimed to determine the clinical significance and microbiological characteristics of MRSA bacteraemia (MRSAB) caused by ST8 and other endemic clones. A total of 281 non-duplicated MRSAB were identified in a medical centre between 2016 and 2018. Sequencing of target genes was performed to determine ST and to confirm ST8 belonging to USA300. Antimicrobial susceptibility testing was performing by using Sensititre standard panel. In total, ST8 accounted for 18.5% of MRSAB ranking after ST239 (31.0%) and ST59 (23.5%). However, it increased to become the most prevalent clone finally. All ST8 isolates belonged to spa clonal complex008, and carried SCCmec IV/IVa, PVL and ACME genes, indicating USA300. ST8/USA300 isolates were highly susceptible to non-β-lactams antibiotics, except fluoroquinolone and erythromycin. ST8/USA300 MRSAB is commonly developed in community settings with either healthcare risks or not (71.2%). Compared to other STs MRSAB, ST8/USA300 MRSAB patients had more diabetes mellitus (50.0%), more admitted from long-term care facility residents (25.0%), had more skin ad soft tissue infection as primary focus (25.0%), and had fewer vascular devices (26.9%) at MRSAB onset. On multivariable analysis, isolates with vancomycin MIC were significantly associated with mortality in the dose–response relationship, rather than STs. This report depicts the clinical features of ST8/USA300 MRSAB and clonal shift from prior endemic clones to ST8/USA300. Our data strongly support long-term surveillance to ascertain whether ST8/USA300 will successfully disseminate and demonstrate its pathogenicity on clinical outcomes.

Background: Invasive fungal diseases (IFD) are a serious threat, but physicians in Asia lack access to many advanced diagnostics in mycology. It is likely that they face other impediments in the management of IFD. A gap analysis was performed to understand the challenges Asian physicians faced in medical mycology. Methods: The Asia Fungal Working Group (AFWG) conducted a web-based survey on management practices for IFD among clinicians in China, India, Indonesia, Philippines, Singapore, Taiwan and Thailand. Findings: Among 292 respondents, 51.7% were infectious disease (ID) specialists. Only 37% of respondents had received formal training in medical mycology. They handled only around 2–4 proven cases of each fungal infection monthly, with invasive candidiasis the most common. For laboratory support, the majority had access to direct microscopy (96%) and histopathology (87%), but galactomannan and azole levels were available to 60% and 25% of respondents, respectively. The majority (84%) used clinical parameters for treatment response monitoring, and 77% followed the Infectious Diseases Society of America guidelines. The majority (84%) did not use the services of an ID physician. Where febrile neutropenia was concerned, 74% of respondents used the empirical approach. Only 30% had an antifungal stewardship program in their hospital. Eighty percent could not use preferred antifungals because of cost. Interpretation: The survey identified inadequacies in medical mycology training, non-culture diagnostics, access to antifungal drugs, and local guidelines as the major gaps in the management of IFDs in Asian countries. These gaps are targets for improvement.

Background/purpose: The clinical, epidemiological, and laboratory factors associated with disease severity and mortality from confirmed leptospirosis patients in Taiwan are not well known. This retrospective study examined patients with suspected leptospirosis admitted to En-Chu-Kong Hospital, a regional teaching hospital in northern Taiwan. Methods: From January 2002 to July 2014, 733 suspected cases were reported to the National Reference Laboratory, 57 of which were identified as laboratory and clinical confirmed. We analyzed the clinical, epidemiological, and laboratory factors associated with disease severity and mortality in 57 cases. Results: The mean age was 59.1 ± 18.2 years, 74% were male, and 49% had occupational contact with soil. The major complications were pulmonary involvement (54%), shock (44%), ventilator support (32%), jaundice (32%), hemorrhage (30%), acute kidney injury (30%), meningitis (11%) and myocarditis (2%). Leptospira santarosai serova Shermani was present in 42 (74%) patients and 37 (58%) patients had severe leptospirosis. Sixteen (28%) patients had concomitant infections, including nine patients with bloodstream infection. The only independent predictor for severe leptospirosis was shock (OR 14.8, 95% CI 2.97–73.59). Eleven patients died (19%). Acute respiratory distress syndrome with severe pulmonary hemorrhage syndrome (6 patients) was present in 55% of the fatal cases. The factors independently related to mortality were prior steroid use (OR 20.2, 95% CI 1.9–217.5) and hemorrhage (OR 71.2, 95% CI 4.9 – >999.9). Conclusion: These results indicate that shock is a predictor of severe leptospirosis, and prior steroid use and hemorrhage are predictors of death from leptospirosis. Keywords: Leptospirosis, Severity, Risk factor, Mortality

Objective: A policy initiated in 2001 by Taiwan's National Health Insurance (NHI) Administration has effectively reduced outpatient antibiotic use except fluoroquinolones (FQs). The influence of differential regulation policy of narrow-spectrum versus broad-spectrum FQs on the prescriptions is unknown. Methods: This study analyzed the claim records of oral FQs prescription at outpatient visits during 2000–2010 using the NHI Research Database and compared prescriptions for narrow-spectrum FQs, which are inactive against Streptococcus pneumoniae and lack formulary restriction, with those for broad-spectrum FQs. Results: Oral antibiotics were prescribed in 13.3% of visits and FQs accounted for 2.2% of them. During the study period the population-based rates of FQ prescription visits to children decreased, which was offset by increased use in the adult and geriatric populations (all p

Abstract Background Inadequate hospital cleaning may contribute to cross-transmission of pathogens. It is important to implement effective cleaning for the safe hospital environment. We conducted a three-phase study using human factors engineering (HFE) approach to enhance environmental cleanliness. Methods This study was conducted using a prospective interventional trial, and 28 (33.3%) of 84 wards in a medical center were sampled. The three-phases included pre-intervention analysis (Phase 1), implementing interventions by HFE principles (Phase 2), and programmatic analysis (Phase 3). The evaluations of terminal cleaning and disinfection were performed using the fluorescent marker, the adenosine triphosphate bioluminescence assay, and the aerobic colony count method simultaneously in all phases. Effective terminal cleaning and disinfection was qualified with the aggregate outcome of the same 10 high-touch surfaces per room. A score for each high-touch surface was recorded, with 0 denoting a fail and 10 denoting a pass by the benchmark of the evaluation method, and the total terminal cleaning and disinfection score (TCD score) was a score out of 100. Results In each phase, 840 high-touch surfaces were collected from 84 rooms after terminal cleaning and disinfection. After the interventions, the TCD score by the three evaluation methods all showed significant improved. The carriage incidence of multidrug-resistant organism (MDRO) decreased significantly from 4.1 per 1000 patient-days to 3.6 per 1000 patient-days (P = .03). Conclusion The HFE approach can improve the thoroughness and the effectiveness of terminal cleaning and disinfection, and resulted in a reduction of patient carriage of MDRO at hospitals. Larger studies are necessary to establish whether such efforts of cleanliness can reduce the incidence of healthcare-associated infection.

Objective Sepsis is the leading cause of in-hospital mortality in the United States (US). Quality improvement initiatives for improving sepsis care depend on accurate estimates of sepsis mortality. While hospital 30-day risk-standardized mortality rates have been published for patients hospitalized with acute myocardial infarction, heart failure, and pneumonia, risk-standardized mortality rates for sepsis have not been well characterized. We aimed to construct a sepsis risk-standardized mortality rate map for the United States, to illustrate disparities in sepsis care across the country. Methods This cross-sectional study included adults from the US Nationwide Inpatient Sample who were hospitalized with sepsis between 1 January 2010 and 30 December 2011. Hospital-level risk-standardized mortality rates were calculated using hierarchical logistic modelling, and were risk-adjusted with predicted mortality derived from (1) the Sepsis Risk Prediction Score, a logistic regression model, and (2) gradient-boosted decision trees, a supervised machine learning (ML) algorithm. Results Among 1,739,033 adults hospitalized with sepsis, 50% were female, and the median age was 71 years (interquartile range: 58–81). The national median risk-standardized mortality rate for sepsis was 18.4% (interquartile range: 17.0, 21.0) by the boosted tree model, which had better discrimination than the Sepsis Risk Prediction Score model (C-statistic 0.87 and 0.78, respectively). The highest risk-standardized mortality rates were found in Wyoming, North Dakota, and Mississippi, while the lowest were found in Arizona, Colorado, and Michigan. Conclusions Wide variation exists in sepsis risk-standardized mortality rates across states, representing opportunities for improvement in sepsis care. This represents the first map of state-level variation of risk-standardized mortality rates in sepsis.

Abstract Background Little is known about risk factors for subsequent infections among vancomycin resistant Enterococcus faecium (VREfm) colonizers, especially characterized by concordant pulsotypes (CP) of paired colonization and infection-related isolates. Methods This case-control study was conducted at a teaching hospital between 2011 and 2014. Targeted patients received active surveillance culture for VREfm by anal swabs at admission. Cases were those who developed VREfm infection within 180 days after colonization of VREfm. Controls were those colonized with VREfm without subsequent VREfm infection. CP were defined by similarities ≥86.7% using pulsed-field gel electrophoresis between paired colonization and infection-related isolates. Results Ninety-seven cases and 194 controls were enrolled. By conditional multivariable logistic regression analysis, the risk factors for subsequent infection among VREfm colonizers were intensive care unit (ICU) admission (adjusted odds ratio [aOR], 9.32; 95% CI, 3.61–24.02), receipt of central venous catheters (CVC) (aOR, 3.38; 95% CI, 1.30–8.82), and utilization of third- and fourth-generation cephalosporins (aOR, 4.06; 95% CI, 1.79–9.20, and aOR, 5.32; 95% CI, 1.85– 10.29, respectively) (all P ≤ 0.01). Fifty-six (57.7%) of case patients belonged to the CP group, which were associated with ICU admission (aOR, 3.74; 95% CI, 1.38–10.13), and infection developing within 30 days after colonization (aOR, 3.34; 95% CI, 1.25–8.91). Conclusions Among VREfm colonizers, being admitted to ICU and receiving CVC or broad spectrum cephalosporins, were the risk factors for subsequent infections. These findings highlight the importance of conducting more strict infection control measures on specific groups of VREfm colonizers.

Background: Cumulative data of case-fatality rates (CFR) of COVID-19 varied across countries. A forecasting model generated based on detailed information from three countries during the initial phase of pandemic showed that progression rates from pneumonia to ARDS (PRPA) varied by country and were highly associated with CFR. We aim to elucidate the impact of the PRPA on COVID-19 deaths in different periods of pandemic. Methods: We used the country-based, real-time global COVID-19 data through GitHub repository to estimate PRPA on the first period (January to June), second period (July to September), and third period (October to December) in 2020. PRPA was used for predicting COVID-19 deaths and assessing the reduction in deaths in subsequent two periods. Results: The estimated PRPA varied widely from 0.38% to 51.36%, with an average of 15.99% in the first period. The PRPA declined to 8.44% and 6.35% in the second and third period. The CFR declined stepwise and was 4.94%, 2.61%, and 1.96%, respectively. Some countries exhibited a decrease in the PRPA from the second to the third period whereas others showed the opposite, particularly where selected viral mutants were prevalent. Overall, the number of observed deaths was lower than that of the predicted deaths in the second and third periods, suggesting an improvement in management of COVID-19 patients. Besides, the degree of improvement depends on the extent of change in PRPA. Conclusion: PRPA is a useful indicator to facilitate decision making and assess the improvement of clinical management and medical capacity by forecasting deaths.

In a multicenter study, we determined a prevalence rate of 4% for azole-resistant Aspergillus fumigatus in Taiwan. Resistance emerged mainly from the environment (TR34/L98H, TR34/L98H/S297T/F495I, and TR46/Y121F/T289A mutations) but occasionally during azole treatment. A high mortality rate observed for azole-resistant aspergillosis necessitates diagnostic stewardship in healthcare and antifungal stewardship in the environment.

Candida tropicalis is the leading cause of non–C. albicans candidemia in tropical Asia and Latin America. We evaluated isolates from 344 patients with an initial episode of C. tropicalis candidemia. We found that 58 (16.9%) patients were infected by fluconazole-nonsusceptible (FNS) C. tropicalis with cross resistance to itraconazole, voriconazole, and posaconazole; 55.2% (32/58) of patients were azole-naive. Multilocus sequence typing analysis revealed FNS isolates were genetically closely related, but we did not see time- or place-clustering. Among the diploid sequence types (DSTs), we noted DST225, which has been reported from fruit in Taiwan and hospitals in Beijing, China, as well as DST376 and DST505–7, which also were reported from hospitals in Shanghai, China. Our findings suggest cross-boundary expansion of FNS C. tropicalis and highlight the importance of active surveillance of clinical isolates to detect dissemination of this pathogen and explore potential sources in the community.