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Background/purpose Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Background: Among the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated. Material and methods: Including adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan. Results: Totally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.

Clostridioides difficile (C. difficile) infection (CDI) is the most common cause of antibiotic-associated diarrhea and one of the common infections in healthcare facilities. In recent decades, ther...

Background/Purpose Ceftaroline, with a unique activity against methicillin-resistant Staphylococcus aureus (MRSA), was not launched in Taiwan before 2019. The in vitro susceptibility data of ceftaroline against important Taiwanese pathogens are lacking. Methods The in vitro susceptibility of ceftaroline against important pathogens collected from 2012 through 2018 were extracted from the Antimicrobial Testing Leadership and Surveillance program. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) to ceftaroline against all isolates. Results During the study period, the in vitro data regarding isolates of S. aureus (n = 2049), Staphylococcus epidermidis (n = 185), Streptococcus pneumoniae (n = 334), Streptococcus pyogenes (n = 170), Haemophilus influenzae (n = 75), Haemophilus parainfluenzae (n = 10) and Klebsiella pneumoniae (n = 680) regardless of hospital sites of collection were analyzed. Among the S. aureus isolates studied, 19.4% showed MICs of 1 mg/L to ceftaroline, and 4.4% showed in vitro susceptible-dose dependent to ceftaroline (all MICs, 2 mg/L). Most of other Gram-positive cocci, all H. influenzae and H. parainfluenzae isolates were susceptible to ceftaroline. By contrast, about one-third (35.9%) of K. pneumoniae isolates, irrespective of infection sources, exhibited non-susceptibility to ceftaroline (MIC range, 0.015–256 mg/L; MIC50 and MIC90 values, 0.12 and 256 mg/L, respectively). Conclusions From the pharmacodynamic perspectives, the ceftaroline dosage of 600 mg as a 2-h intravenous infusion every 8 h is effective against all S. aureus and other Gram-positive isolates regardless of acquisition sites in Taiwan. Before ceftaroline is prescribed in treatment of the patient with Gram-negative infection, a cautious evaluation about patient's healthcare-associated factor is warranted.

Introduction To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination. Areas covered This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS. Expert opinion : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity. Plain language summary What is the context?Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines.TTS mainly occurs in patients aged 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated.What is the impact?TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.

Objectives The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017–2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic. Methods During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes. Results Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23. Conclusion The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.

Introduction: Scrub typhus is one of the most underdiagnosed and under-reported febrile illnesses requiring hospitalization, mainly occurring in Southeast and East Asia and the Pacific Islands, in ...

Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.

Background/purpose: Tuberculosis (TB) in the elderly population remains a major challenge in areas with intermediate disease burden like Taiwan. Despite the increasing burden and high risks of TB in the elderly population, particularly those living in long-term care facilities (LTCFs), diagnostic testing for latent tuberculosis infection (LTBI) has not been carefully evaluated in this group. This study aimed to investigate the prevalence and predictors of LTBI in older adults living in LTCFs. Methods: Older adults living in seven LTCFs in Taiwan were prospectively enrolled between January and July 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-tube was used to determine presence of LTBI. Predictors for LTBI were analyzed. Results: A total of 258 participants were enrolled, including 240 older residents (mean age, 81.6 years; male, 51.2%) and 18 employees (mean age, 64.8 years; male, 22.2%). The proportion of independent status in ambulation assessments significantly declined with aging (p

Objectives We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in treating coronavirus disease 2019 (COVID-19). Methods PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020. Results Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group [OR = 1.68 (95% CI 1.18–2.40)], with no significant difference observed between the 10 day and placebo groups [OR = 1.23 (95% CI 0.90–1.68)]. Patients receiving remdesivir revealed a greater likelihood of discharge [10 day remdesivir versus control: OR = 1.32 (95% CI 1.09–1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28–2.35)] and recovery [10 day remdesivir versus control: OR = 1.29 (95% CI 1.03–1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31–2.48)] than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events. Conclusions Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.

Objectives Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. Methods An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. Results 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. Conclusion The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.

Objective To determine serogroups, multilocus sequence typing (MLST) of Listeria monocytogenes isolates and analyze clinical characteristics of these clones focusing on non-perinatal cases. Methods From 2000 to 2015, we analyzed 123 human listeriosis cases at a medical center in northern Taiwan using PCR serogrouping, MLST, and clinical presentations. Results The annual incidence of listeriosis increased since 2005 with a peak in 2008 (0.2 per 1000 admission) and decreased thereafter. Of the 115 non-perinatal listeriosis cases, we found a male predominance (60%) with an average age of 63.9 years old (standard deviation: 15.3 years), and almost all patients had underlying conditions including malignancies (61.7%), steroid usage (39.1%), diabetes mellitus (31.3%), renal insufficiency (27.8%), and liver cirrhosis (17.4%). Clinical presentations included bacteremia (74.8%), neurolisteriosis (20.0%), and spontaneous bacterial peritonitis (5.2%). The most frequently identified serogroup-sequence types (ST) were IIB-ST87 (30.9%), followed by IIA-ST378 (16.3%) and IIA-ST155 (14.6%). The 30-day all-cause mortality of non-perinatal listeriosis was 25.2% and was associated with age (Hazard ratio: 1.04, 95% C.I. = 1.01–1.07, p = 0.021), steroid usage (Hazard ratio: 2.54, 95% C.I. = 1.06–6.11, p = 0.038) and respiratory distress at presentation (Hazard ratio: 2.59, 95% C.I. = 1.05–6.39, p = 0.038); while no association was found with serogroups (IIA, IIB, and IVB) or three major ST types by multivariable analysis. All 8 mothers of perinatal listeriosis patients survived and three neonates died (mortality, 37.5%), and IIB-ST87 was the major type (62.5%). Conclusion Predominant strains in Taiwan could cause significant morbidity and mortality. Further disease monitoring and source surveillance are warranted despite a declining trend of human listeriosis in Taiwan.

Background/purpose As the incidence of fungal infections in China increases, the demand for rapid and accurate diagnosis of mycoses is growing. Yet, information on current diagnostic capacity is scarce. Methods An online survey was conducted in February 2018 to collect information on mycology testing from tertiary care hospitals across China. Responses from 348 hospitals were analyzed, and a scoring system was designed and employed to assess the overall diagnostic capacity. Results Most of the surveyed hospitals did not have separate laboratory space, manpower, or equipment dedicated for fungal testing. Conventional staining methods were widely available (>70%), whereas GMS and fluorescent staining were less common. Fungal identification services were offered mostly with chromogenic medium, morphological characterization or automated identification systems, other than more advanced methods such as MALDI-TOF MS and DNA sequencing. Fungal serology testing was available in 81.1%, with G test being the most often used. Though 91.8% of the respondents had the ability to perform antifungal susceptibility testing for yeasts, less than 13% conducted such testing for molds. The percentage of laboratories participating in External Quality Assessment programs and research was 57.5% and 32.5%, respectively. The average score for the 348 surveyed hospitals was 37.2 (out of a maximum of 89 points), with only 15 hospitals scoring >60, suggesting a general lack of high-quality mycology laboratories. Conclusions The overall clinical testing capacity for fungal infection in China is insufficient. More investment and training efforts are warranted to establish centers of excellence and promote access to high-quality diagnostic services.

Objectives To determine the minimum inhibitory concentration (MIC) distribution, epidemiological cut-off (ECOFF) values and clinical breakpoints (CBPs) of nemonoxacin, a non-fluorinated quinolone, for community-acquired pneumonia (CAP)-related Streptococcus pneumoniae and Staphylococcus aureus. Methods We pooled the susceptibility and clinical data of CAP patients enrolled in five clinical trials conducted in three countries from 2006 to 2017. Published pharmacokinetic (PK) profiles of oral (500 mg) and intravenous (IV) (500, 650 and 750 mg) nemonoxacin formulations and pharmacodynamic (PD) parameters of the two aforementioned CAP-related Gram-positive cocci (GPC) were used to determine plausible CBPs. Moreover, nemonoxacin MIC distributions of CAP-relatedS. pneumoniae (n = 1800) and S. aureus (n = 2000) isolates were obtained to evaluate ECOFF values using a visual estimation approach and ECOFFinder. Results More than 92% of patients with CAP caused byS. pneumoniae or S. aureus with nemonoxacin MICs ≤ 0.25 mg/L presented positive clinical and microbiological outcomes. The ECOFF, MIC90 and MIC99 values of nemonoxacin were, respectively, 0.06, 0.125 and 1 mg/L for S. pneumoniae and 0.125, 1 and 8 mg/L for S. aureus. Based on differences in the PK profiles of oral and IV formulations, PD parameters of nemonoxacin for these CAP-GPC and clinical in vivo efficacy data, tentative CBPs of 0.5, 0.5 and 1 mg/L, respectively, were established for the 500 mg oral and 500 mg and 750 mg IV nemonoxacin formulations for S. pneumoniae, and 0.25, 0.5 and 1 mg/L for S. aureus. Conclusion This study provides plausible nemonoxacin CBPs for two important CAP-GPC.

Background/purpose Rapid and accurate identification of pathogens and their antibiotic resistance directly from flagged blood cultures can aid clinicians in optimizing early antibiotic treatment and improve the clinical outcomes, especially in settings associated with high rates of bloodstream infection caused by vancomycin-resistant Enterococci (VRE) and carbapenem-resistant Enterobacteriaceae (CRE). We compared the results of the BioFire FilmArray Blood Culture Identification (BCID) panel with those of conventional methods for identifying the pathogens and their antibiotic susceptibility status. Methods In total, 100 randomly selected positive blood cultures (BACTEC Plus Aerobic/F bottles or BACTEC Anaerobic Lytic/10 bottles) were analyzed. The pathogen detection efficiency of FilmArray BCID panel was compared with that of conventional method using MALDI-TOF MS system (Bruker MALDI Biotyper) and susceptibility testing by the Vitek 2 system. The sequencing analysis of antibiotic resistance genes was performed for discrepant results obtained from MALDI Biotyper and Vitek 2. Results Among the 100 positively flagged blood cultures, 94% of FilmArray BCID panel results were consistent with the MALDI Biotyper results. All five VRE isolates positive for vanA/vanB genes, 10 of 12 Staphylococcus species positive for mecA gene, and only one Klebsiella pneumoniae isolate positive for K. pneumoniae carbapenemase gene (blaKPC) detected in the FilmArray BCID panel were also concordant with results by the results by conventional susceptibility testing/molecular confirmation. Conclusions The FilmArray BCID panel results not only demonstrated good correlation with conventional blood culture identification and susceptibility results but also provided results rapidly, especially for the early detection of MRSA, VRE and blaKPC–mediated CRE.

Highlights • Performance of serological tests detecting SARS-CoV-2 antibodies is disease course dependent. • Detection sensitivity of rapid antibody tests with lateral flow immunoassay for COVID-19 reached 100% after 3 weeks of symptom onset. • COVID-19 patients with pneumonia exhibited earlier seroconversion than those without pneumonia. • Prolonged viral shedding after seroconversion with a median duration of 14 days was observed. • Serological testing may be a useful tool in addition to rRT-PCR for the diagnosis of COVID-19., SUMMARY Objectives: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. Methods: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. Results: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. Conclusion: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.

Lemierre's syndrome, also known as post-anginal septicemia or necrobacillosis, is characterized by bacteremia, internal jugular vein thrombophlebitis, and metastatic septic emboli secondary to acute pharyngeal infections. Modern physicians have "forgotten" this disease. The most common causative agent of Lemierre's syndrome is Fusobacterium necrophorum, followed by Fusobacterium nucleatum and anaerobic bacteria such as streptococci, staphylococci, and Klebsiella pneumoniae. The causative focus mostly originated from pharyngitis or tonsillitis, accounting for over 85% of the cases of Lemierre's syndrome. Pneumonia or pleural empyema is the most common metastatic infection in Lemierre's syndrome. Antimicrobial therapy should be prescribed for 3-6 weeks. The treatment regimens include metronidazole and β-lactam antibiotics. In recent years, the antibiotic stewardship program has resulted in decreased antibiotic prescription for upper respiratory tract infections. The incidence of Lemierre's syndrome has increased over the past decade. F. necrophorum is an underestimated cause of acute pharyngitis or tonsillitis. A high index of suspicion is required for the differential diagnosis of acute tonsillopharyngitis with persistent neck pain and septic syndrome.

Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

Background: Clostridium difficile infection (CDI) is increasing in children. We aimed to compare the clinical characteristics between CDI and colonization and to identify the risk factors for severe diseases of CDI in children. Method: We retrospectively reviewed 124 children (1–18 years old) from 2011 to 2018. CDI was defined as diarrhea (≥3 loose stool in the past 24 h) with confirmed toxigenic strain. Colonization was defined as presence of C. difficile without clinical symptoms. Severe diseases included ileus, acute kidney injury, gastrointestinal bleeding or mortality. Patients younger than 1 year old and coinfections with other enteric pathogens were excluded. Results: Among 124 patients with C. difficile identified, 49 of them fulfilled CDI definition and 75 had C. difficile colonization. Children with CDI were more likely to present with watery (74% vs. 1%, p

Background Mycobacterium chimaera, one of the Mycobacterium avium complex (MAC) members, was recently identified using modern gene sequencing analysis. Unlike M. avium and M. intracellulare, little is known about the clinical features, antimicrobial susceptibilities, and treatment outcomes of M. chimaera lung disease. Methods This study was conducted in a medical center from December 2012 to July 2015. Patients who fulfilled the 2007 ATS/IDSA diagnostic criteria for nontuberculous mycobacterial lung disease were enrolled. M. chimaera isolates were identified based on the findings of sequencing of rpoB gene, the internal transcribed spacer (ITS) region of the 16S–23S rRNA gene, and the heat-shock protein 65 gene (hsp65). Minimum inhibitory concentrations (MICs) of 13 antimicrobial agents were determined. Results During the study period, 247 patients with MAC lung disease were identified, and 11.3% (28/247) of the patients had lung disease caused by M. chimaera. Among these patients, 17 (60.7%) were female, and their median age was 72.5 (40–100) years. All M. chimaera isolates were susceptible to clarithromycin and rifabutin. All the isolates were resistant to moxifloxacin and only 10 (35.7%) and 2 (7.1%) were susceptible to amikacin and linezolid, respectively. Of the nine patients who received macrolide-based regimens, more achieved radiographic resolution than those treated with non-macrolide-based regimens (66.7% vs. 15.8%, P = 0.013), and they tended to have better survival (P = 0.10). Conclusions A substantial portion (11.3%) of MAC lung disease cases were caused by M. chimaera, and treatment with macrolide-based regimens resulted in better clinical outcomes for patients with M. chimaera lung disease.

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

Background/purpose: This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy. Methods: All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus. Results: During the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack of response to anti-fungal treatment (P

As more than two billion people possibly have a latent tuberculosis (LTB) infection, early LTB diagnosis is crucial for the efficient control and elimination of tuberculosis (TB). The aim of this study is to detect the serum antibody responses to dormancy-related DosR regulon antigens of Mycobacterium tuberculosis for the diagnosis of active and latent TB infections. A membrane array with 25 latency antigens detected by silver-enhanced gold nanoparticles was used to determine the corresponding cognate antibody levels in clinical serum samples from healthy controls, TB patients, and individuals with LTB. The array is sized to fit into a 24-well ELISA plate and follows an ELISA-like experimental procedure without expensive instrumentation. Linear discriminant analysis (LDA) of the resulting antibody profiling data set identified a panel of nine DosR antigens with significant discriminatory capability among different subjects with ≥90% sensitivity, specificity, and overall accuracy. Furthermore, the high predictive performance validated by an independent test sample set reflects the robustness and reliability of the LDA classification model. Our current data demonstrate that the nine DosR antigen combination associated with the proposed membrane array platform is a clinically feasible approach for distinguishing different TB infection statuses. The proposed methodology in this study could be further developed for multiple disease serodiagnoses with high sensitivity and specificity.

Background: Timely diagnostic investigation to establish the microbial etiology of pneumonia is essential to ensure the administration of effective antibiotic therapy to individual patients. Methods: We evaluated a multiplex PCR assay panel, the FilmArray® pneumonia panel (FilmArray PP, BioFire Diagnostics), for detection of 35 respiratory pathogens and resistance determinants and compared the performance of the standard-of-care test in intensive care unit patients with lower respiratory tract infections. Results: Among the 59 endotracheal aspirates and bronchoalveolar lavage specimens obtained from 51 adult patients, FilmArray PP was effective in detecting respiratory bacterial pathogens with an overall positive percent agreement of 90% (95% confidence interval [CI], 73.5–97.9%) and negative percent agreement of 97.4% (95% CI, 96.0–98.4%). FilmArray PP semi-quantitative reporting demonstrated a concordance rate of 53.6% for the culture-positive specimens and 86.3% for the culture-negative specimens. FilmArray PP detected 16 viral targets, whereas the conventional viral isolation failed, except influenza A, which showed 100% concordance with PCR. Coinfections were detected in 42.3% of the specimens. Substantial discrepancies were observed in identifying antimicrobial resistance gene targets and in the susceptibility testing. However, FilmArray PP may still be useful at the early stage of pneumonia before culture and susceptibility test reports are available. Consequently, the results of FilmArray PP might alter the antibiotic prescription in 40.7% of the patients. Conclusions: FilmArray PP offers a rapid and sensitive diagnostic method for lower respiratory tract infections. However, clinical correlation is advised to determine its significance in interpreting multiple pathogens and detection of genes involved in antimicrobial resistance. Keywords: FilmArray pneumonia panel, Respiratory failure, Pneumonia, Pathogen detection, Resistant genes, Performance

Probiotic supplements have been used to decrease the gut carriage of antimicrobial-resistant Enterobacterales through changes in the microbiota and metabolomes, nutrition competition, and the secretion of antimicrobial proteins. Many probiotics have shown Enterobacterales-inhibiting effects ex vivo and in vivo. In livestock, probiotics have been widely used to eradicate colon or environmental antimicrobial-resistant Enterobacterales colonization with promising efficacy for many years by oral supplementation, in ovo use, or as environmental disinfectants. In humans, probiotics have been used as oral supplements for infants to decease potential gut pathogenic Enterobacterales, and probiotic mixtures, especially, have exhibited positive results. In contrast to the beneficial effects in infants, for adults, probiotic supplements might decrease potentially pathogenic Enterobacterales, but they fail to completely eradicate them in the gut. However, there are several ways to improve the effects of probiotics, including the discovery of probiotics with gut-protection ability and antimicrobial effects, the modification of delivery methods, and the discovery of engineered probiotics. The search for multifunctional probiotics and synbiotics could render the eradication of “bad” Enterobacterales in the human gut via probiotic administration achievable in the future.

Objectives This study evaluated the effectiveness of two major citizens’ mobilized intervention strategies - facemasks and alcohol-based hand hygiene and their changes from the 2003 SARS outbreak to the 2020 COVID-19 pandemic (pdmCOVID-19). Methods We surveyed 2,328 Taiwanese from July 29 to August 6, 2020, assessing demographics, information sources, and practice of preventive behaviors from the 2003 SARS or 2009 pandemic influenza H1N1 (2009pdmH1N1) era to the current pdmCOVID-19 as well as post-survey intention to continue preventive practices. Logistic regression was employed to identify characteristics associated with close adherence to preventive behavior practices in 2020. Results About 70.2% of participants adhered closely to recommended preventive behavior practices. Compared with 2003SARS/2009pdmH1N1, there was a significant increase in the use of facemasks during pdmCOVID-19 (66.6% vs. 99.2% [indoors], p

Highlights • A case of transient existence of SARS-CoV-2 RNA in the respiratory tract with the absence of anti-SARS-CoV-2 antibody response • The SARS-CoV-2 RNA was absent in the six respiratory specimens that were subsequently tested. • Anti-SARS-CoV-2 IgM and IgG were absent in the acute and convalescent sera., We report a patient who had travelled to Japan presented mild respiratory symptom during the COVID-19 infection outbreak period. There was transient existence of SARS-CoV-2 RNA in his oropharynx. The RNA was absent in the six respiratory specimens that were subsequently tested. Anti-SARS-CoV-2 antibody response in the acute and convalescent sera were absent. The reported case indicates that transient colonization of SARS-CoV-2 in the upper respiratory tract is possible without inciting any antibody response against the virus.

A 46-year-old woman presented to the emergency department with 2-day fever and cough at seven days after returning from Macau. COVID-19 and pneumonia was diagnosed based on the positive real-time RT-PCR tests for oropharyngeal swab samples and the presence of anti-SARS-COV-2 IgG starting from the illness day 11 and post-exposure 18–21 days.

Objective: This retrospective study investigated clinical manifestations of candidemia caused by uncommon Candida species and antifungal susceptibility of the isolates in a regional hospital in Taiwan. Methods: The uncommon Candida species was initially defined as Candida species other than C. albicans, C. tropicalis, C. glabrata complex, C. parapsilosis complex and C. krusei. All uncommon Candida isolates were identified and confirmed by molecular methods. In vitro susceptibility testing of the uncommon Candida species to nine antifungal agents was conducted using the broth microdilution method with the Sensititre YeastOne (SYO) system (Trek Diagnostic Systems, Ltd., East Grimstead, UK). Results: Twenty-one patients, comprising 11 males and 10 females with a median age of 69 years, were recruited. Cancer (n = 11) was the most common underlying disease, 19 (90.5%) cases had prior antibiotic exposure, and only two patients had prior antifungal use. The overall in-hospital mortality rate was 38.1% (n = 8). C. guilliermondii (n = 11) was the most common pathogen, followed by C. curvata (n = 3). C. guilliermondii isolates exhibited relatively high rates of azole minimum inhibitory concentrations (MICs) above epidemiological cut-off values (ECVs), whereas C. pelliculosa and C. lusitaniae isolates all remained susceptible to azoles. All three C. curvata isolates had high caspofungin (>8 mg/L) and fluconazole MICs (8 mg/L) and could be defined as multidrug-resistant. Conclusions: Uncommon Candida species frequently exhibit high rates of non-susceptibility to antifungals. Identification of all Candida isolates at the species level from blood samples is of value for treatment. Keywords: Candidemia, Uncommon candida species, Healthcare-associated infection, Antifungal susceptibility testing, Azoles, Echinocandin

Objectives: The incidence of Pneumocystis pneumonia (PCP) has been increasing among non-HIV-infected patients. Here, we investigated the clinical characteristics, treatment outcomes, and prognostic factors of PCP in non-HIV-infected patients. Patients and methods: Information on clinical characteristics, treatment outcomes, and prognostic factors of PCP patients who were treated at a medical center in northern Taiwan from October 2015 to October 2016 were retrieved from medical records and evaluated. Results: Among the patients with PCP included in the study, 84 were non-HIV-infected and 25 were HIV-infected. Non-HIV-infected patients with PCP had a longer duration between radiographic findings and treatment (P

Purpose: Fecal carriage of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published. Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage. Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3-22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6-24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4-305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0-22.5) and stroke (aOR: 18.0, 95% CI: 1.6-207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage. Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.

A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. Most of these antibiotics display good in vitro activity against the producers of Ambler class A, C, and D β-lactamase, although avibactam and vaborbactam are not active in vitro against metallo-β-lactamase (MβL) enzymes. Nevertheless, in vitro efficacy against the producers of some or all class B enzymes (New Delhi MβL, Verona integron-encoded MβL, etc) has been shown with cefepime-zidebactam, aztreonam-avibactam, VNRX-5133, cefiderocol, plazomicin, and eravacycline. As of Feburary 2019, drugs approved for treatment of some CRE-related infections by the US Food and Drug Administration included ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, and eravacycline. Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.

Objective The aim of this study was to investigate the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria from seven intensive care units in Taiwan in 2016.

Background/purpose: This study investigated the distribution and persistence of multidrug resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and multidrug-resistant Acinetobacter baumannii (MDRAB) in six long-term care facilities (LTCFs). Methods: We investigated the distribution of MDROs in residents of six LTCFs and their environments from January to December 2016 (intervention period). Active surveillance of colonization of MDROs was performed by culturing rectal and nasal swab samples from the residents every three months. Multilocus sequence typing (MLST) was conducted, and genes for panton-valentine leukocidin (PVL) from MRSA isolates were determined. Results: A total of 521 samples were positive for MDROs, and MRSA was the most common organism (65.1%), followed by MDRAB (11.3%), carbapenem-resistant Klebsiella pneumoniae (11.1%), carbapenem-resistant Escherichia coli (4.6%), and carbapenem-resistant P. aeruginosa (2.1%, n = 11). By a linear regression model, positive MRSA isolates from the environment were found to be statistically significant and associated with the number of colonized LTCF residents (p = 0.01), while the timing of the surveillance culture was not (p = 0.227). The main MLST types associated with PVL-production were sequence type (ST) 59, (40.0%, 24/60), ST30 (21.4%, 3/14), ST8 (87.5%, 14/16), and ST45 (3.6%, 1/28). The susceptibility rates of tetracycline (96.7%), trimethoprim-sulfamethoxazole (96.7%), and ciprofloxacin (81.7%) were statistically significant and higher in MRSA ST59, compared to the rates in MRSA ST45 isolates. Conclusions: MRSA was the most commonly colonized MDRO, both in the LTCF residents and in the environment, followed by MDRAB and carbapenem-resistant K. pneumoniae. Keywords: Multidrug-resistant organisms, Long-term care facility, Methicillin-resistant Staphylococcus aureus, Sequence type

Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti−SARS−CoV−2 total and IgG antibodies in all participants were determined by Roche Elecsys® Anti−SARS−CoV−2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN recomLine SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.

The emergence of carbapenem-resistant Enterobacterales (CRE) has become a major public health concern. Moreover, its colonization among residents of long-term care facilities (LTCFs) is associated with subsequent infections and mortality. To further explore the various aspects concerning CRE in LTCFs, we conducted a literature review on CRE colonization and/or infections in long-term care facilities. The prevalence and incidence of CRE acquisition among residents of LTCFs, especially in California, central Italy, Spain, Japan, and Taiwan, were determined. There was a significant predominance of CRE in LTCFs, especially in high-acuity LTCFs with mechanical ventilation, and thus may serve as outbreak centers. The prevalence rate of CRE in LTCFs was significantly higher than that in acute care settings and the community, which indicated that LTCFs are a vital reservoir for CRE. The detailed species and genomic analyses of CRE among LTCFs reported that Klebsiella pneumoniae is the primary species in the LTCFs in the United States, Spain, and Taiwan. KPC-2-containing K. pneumoniae strains with sequence type 258 is the most common sequence type of KPC-producing K. pneumoniae in the LTCFs in the United States. IMP-11- and IMP-6-producing CRE were commonly reported among LTCFs in Japan. OXA-48 was the predominant carbapenemase among LTCFs in Spain. Multiple risk factors associated with the increased risk for CRE acquisition in LTCFs were found, such as comorbidities, immunosuppressive status, dependent functional status, usage of gastrointestinal devices or indwelling catheters, mechanical ventilation, prior antibiotic exposures, and previous culture reports. A high CRE acquisition rate and prolonged CRE carriage duration after colonization were found among residents in LTCFs. Moreover, the patients from LTCFs who were colonized or infected with CRE had poor clinical outcomes, with a mortality rate of up to 75% in infected patients. Infection prevention and control measures to reduce CRE in LTCFs is important, and could possibly be controlled via active surveillance, contact precautions, cohort staffing, daily chlorhexidine bathing, healthcare-worker education, and hand-hygiene adherence.

Objectives: Decreased susceptibility to ceftazidime/avibactam (CZA) and ceftaroline (CPT) has been reported during antimicrobial resistance surveillance and therapy. Conventional laboratories are unable to provide timely susceptibility testing for CZA and CPT because these antimicrobial agents are not incorporated in automated susceptibility testing systems. Methods: We evaluated Etest and the Sensititre broth microdilution (BMD) method for testing CZA against carbapenem-resistant Gram-negative bacilli and CPT against important Gram-positive cocci bloodstream isolates. Genotypes of carbapenemases in Enterobacterales were also determined using the Xpert® Carba-R assay. Results: Etest showed ≥90% agreement with Sensititre BMD for carbapenem-resistant Klebsiella pneumoniae (CRKP) (n = 187), carbapenem-resistant Escherichia coli (CREC) (n = 28) and Streptococcus pneumoniae (n = 35); however, the very major error rate exceeded 3%. Agreement between Etest and Sensititre BMD was

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

Since the initial emergence of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province, China, a rapid spread of the disease occurred around the world, rising to become an international global health concern at pandemic level. In the face of this medical challenge threatening humans, the development of rapid and accurate methods for early screening and diagnosis of COVID-19 became crucial to containing the emerging public health threat, and prevent further spread within the population. Despite the large number of COVID-19 confirmed cases in China, some problematic cases with inconsistent laboratory testing results, were reported. Specifically, a high false-negative rate of 41% on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays was observed in China. Although serological testing has been applied worldwide as a complementary method to help identify SARS-CoV-2, several limitations on its use have been reported in China. Therefore, the use of both qRT-PCR and serological testing in the diagnosis of COVID-19 in China and elsewhere, presented considerable challenges, but when used in combination, can be valuable tools in the fight against COVID-19. In this review, we give an overview of the advantages and disadvantages of different molecular techniques for SARS-CoV-2 detection that are currently used in several labs, including qRT-PCR, gene sequencing, loop-mediated isothermal amplification (LAMP), nucleic acid mass spectrometry (MS), and gene editing technique based on clustered regularly interspaced short palindromic repeats (CRISPR/Cas13) system. Then we mainly review and analyze some causes of false-negative qRT-PCR results, and how to resolve some of the diagnostic dilemma.

BackgroundMycobacterium abscessus (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB.MethodsWe performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010–2017 at seven hospitals across Taiwan.ResultsIn total, 183 (49.3%) isolates were M. abscessus subsp. abscessus (MAB-a), 187 (50.4%) were M. abscessus subsp. massiliense (MAB-m), and 1 (0.3%) was M. abscessus subsp. bolletii (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%.ConclusionsThe dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.

Background/purpose This study aimed to investigate the clinical characteristics and outcomes of bacteremia caused by Haemophilus and Aggregatibacter species in patients who were treated at a medical center between 2006 and 2018. Methods Haemophilus and Aggregatibacter isolates were identified up to the species level using Bruker Biotyper MALDI-TOF analysis and ancillary 16S rRNA gene sequencing analysis (in case of ambiguity). Clinical characteristics and outcomes of patients with bacteremia caused by these organisms were evaluated. Results Sixty-five Haemophilus and Aggregatibacter species isolates causing bacteremia were identified from nonduplicated patients, including 51 (78.5%) Haemophilus influenzae, 6 (9.2%) Haemophilus parainfluenzae, 1 (1.5%) Haemophilus haemolyticus, 3 (4.6%) A. aphrophilus, and 4 (6.2%) A. segnis. Hospital mortality was observed in 18 (28.1%) of 64 patients with bacteremia caused by Haemophilus (n = 57) and Aggregatibacter species (n = 7). The majority of patients with bacteremia had community-acquired disease with low severity. The average Sequential Organ Failure Assessment (SOFA) score was low (4.4 ± 4.7). But, a higher SOFA score (adjusted odds ratio 2.5, 95% confidence interval 1.22–5.12; P = 0.01) was an independent factor predicting poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia (n = 39). Conclusions The overall hospital mortality of 28.1% was observed among patients with bacteremia due to Haemophilus and Aggregatibacter species. A higher SOFA score was and independent predictor of poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia.

In addition to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection itself, an increase in the incidence of antimicrobial resistance poses collateral damage to the current status of the COVID-19 (coronavirus disease 2019) pandemic. There has been a rapid increase in multidrug-resistant organisms (MDROs), including extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae, carbapenem-resistant New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), pan-echinocandin-resistant Candida glabrata and multi-triazole-resistant Aspergillus fumigatus. The cause is multifactorial and is particularly related to high rates of antimicrobial agent utilisation in COVID-19 patients with a relatively low rate of co- or secondary infection. Appropriate prescription and optimised use of antimicrobials according to the principles of antimicrobial stewardship as well as quality diagnosis and aggressive infection control measures may help prevent the occurrence of MDROs during this pandemic.

Highlights • Improved serological detection of specific antibodies against SARS-CoV-2 can help estimate the true number of infections. • The seroprevalence can vary according to different sites and the seroprevalence can increase with time in the longitudinal follow-up. • The seroprevalence of healthcare workers wearing adequate personal protective equipment is thought to not be higher than other groups. • Seroprevalence can vary according to different populations, such as pregnant women and hemodialysis patients, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has led to a global pandemic. However, the majority of currently available data are restricted to laboratory-confirmed cases for symptomatic patients, and the SARS-CoV-2 infection can manifest as an asymptomatic or mild disease; therefore, the true extent of the burden of COVID-19 can be underestimated. Improved serological detection of specific antibodies against SARS-CoV-2 can help estimate the true number of infections. This article comprehensively reviewed the associated literature and provides updated information regarding the seroprevalence of the anti-SARS-CoV-2 antibody. The seroprevalence can vary according to different sites and the seroprevalence can increase with time in the longitudinal follow-up. Although healthcare workers (HCWs), especially those caring for COVID-19 patients, are considered as a high-risk group, the seroprevalence of a HCW wearing adequate personal protective equipment is thought to not be higher than other groups. With regard to sex, no statistical difference has been found between male and female subjects. Some, but not all, studies have shown that children have a lower risk than other age groups. Finally, seroprevalence can vary according to different populations, such as pregnant women and hemodialysis patients; however, limited studies have examined these associations. Furthermore, continued seroprevalence surveillance is warranted to estimate and monitor the growing burden of COVID-19.

This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4–99.0%), Abbott Test (94.0%, 89.1–96.8%), Wondfo Test (91.4%, 85.8–94.9%), ASK Test (97.4%, 93.4–99.0%), and Dynamiker Test (90.1%, 84.3–94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3–99.7%) for the Roche Test, 97.9% (95% CI, 94.8–99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1–100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.

This study evaluated the performance of the Xpert MTB/RIF Ultra assay (Xpert Ultra) to detect smear-negative pulmonary tuberculosis (PTB). Xpert Ultra assay was prospectively performed using bronchial washing fluid (BWF) in comparison to COBAS TaqMan MTB (COBAS) assay and mycobacterial culture. Of the 165 enrolled participants, 27 (16.4%) had PTB based on composite reference standard and 16 (9.7%) had culture-confirmed PTB. By the composite reference standard of PTB, the sensitivity of Xpert Ultra (63.0, 95% confidence interval, CI, 42.4-80.6%) was higher than the COBAS assay (25.9%, P = 0.006), BWF-culture (33.3%, P = 0.029) and sputum-culture (37.0%, P = 0.057). Meanwhile, the specificity of Xpert Ultra was 99.3% which was slightly lower than the 100.0% specificity of the COBAS assay (P = 1.000) and cultures (P = 1.000). Against the reference standard of culture-confirmed PTB, Xpert Ultra also had a higher sensitivity (62.5, 95% CI, 35.4-84.8%) than the COBAS assay (31.3%, P = 0.077) and was similar to BWF-culture (56.3%, P = 0.719) and sputum-culture (62.5%, P = 1.000). However, one subject with previously treated old PTB had a false-positive result on the Xpert Ultra assay. This prospective study showed Xpert Ultra assay using BWF had better sensitivity than COBAS assay and mycobacterial cultures but could represent a false positive in patients with inactive old PTB.