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Background/purpose: Early recognition of causative pathogens is critical for the appropriate management of central nervous system infection and improved outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire® ME Panel, BioFire Diagnostics) is the first U.S. Food and Drug Administration (FDA)-approved multiplex PCR assay that allows the rapid detection of 14 pathogens, including bacteria (n = 6), viruses (n = 7), and fungi (n = 1), from cerebrospinal fluid (CSF). The performance of the panel is expected to be dependent on the epidemiology of M/E in different geographical regions. Methods: In this preliminary study, we used the BioFire® ME Panel in 42 subjects who presented to the emergency department with symptoms of M/E in our hospital. The results were compared to conventional culture, antigen detection, PCR, and various laboratory findings. Results: The panel detected six positive samples, of which five were viral and one bacterial. We observed an overall agreement rate of 88% between the BioFire® ME Panel results and the conventional methods. There were no false-positive findings, but five discordant results were observed for enterovirus, herpes simplex virus type 1, Escherichia coli, and Cryptococcus species. Conclusions: The BioFire® ME Panel performed equivalently to the traditional PCR methods for virus detection, and better than bacterial cultures. This revolutionary system represents a paradigm shift in the diagnosis of M/E and may aid in the rapid identification of community-acquired M/E. However, the usefulness of this tool is limited in regions with a high prevalence of infectious M/E caused by microorganisms not included in the panel. Keywords: BioFire® ME panel, Encephalitis, Emergency department, Meningitis, Multiplex PCR assay

Background: The aim of this study was to investigate the performance of the Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Vitek MS systems for identification of genetically-confirmed blood isolates of Candida tropicalis that had been grown on several types of culture media commonly used for primary fungal isolation. Methods: Isolates included 105 from the National China Hospital Invasive Fungal Surveillance Net program (CHIF-NET) and 120 from National Taiwan University Hospital (NTUH). Culture media tested for CHIF-NET isolates included trypticase soy agar supplemented with 5% sheep blood (BAP), Sabouraud dextrose agar (SDA-C), CHROMagar, China blue agar (CBA), chocolate agar supplemented with vancomycin (CAP-VA), and MacConkey agar (MAC). Culture media used for NTUH isolates included BAP, SDA, CHROMagar, eosin methylene blue (EMB), inhibitory mold agar (IMA), Mycosel agar, and cornmeal agar (CMA). Results: The Bruker Biotyper correctly identified all CHIF-NET isolates to the species level on all six agar media tested and correctly identified the majority of NTUH isolates with the exception of isolates grown on SDA (85.8%) and CMA (52.5%). The Vitek MS system correctly identified all CHIF-NET isolates to the species level with the exception of isolates grown on CHROMagar (84.8%), and correctly identified the majority of NTUH isolates with the exception of isolates grown on SDA (51.7%), Mycosel agar (57.5%), and CMA (9.2%) for NTUH isolates. Conclusion: Clinical microbiologists should be aware that different culture media can affect the performance of the Bruker Biotyper MALDI-TOF MS and Vitek MS systems in identifying C. tropicalis. Keywords: Candida tropicalis, MALDI-TOF MS, Bruker Biotyper, Vitek MS, Culture media

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

Background/purpose: This study investigated the impact of implementing ventilator-associated pneumonia (VAP) bundle care on the rates of VAP in intensive care units (ICUs) in Taiwan. Methods: A total of 10 ICUs (bed number, 170), including surgical (SICUs) (n = 7), cardiovascular/surgical (CV/S-ICUs) (n = 1), and medical ICUs (MICUs) (n = 2) from 10 hospitals (7 medical center hospitals and 3 regional hospitals) were enrolled in this quality-improvement project. This study was divided into the pre-intervention phase (1st January, 2012–31st July, 2013) and the intervention phase (1st August, 2013–31st October, 2014). Results: Among the 10 hospitals, the overall rates (cases per 1000 ventilator-days) of VAP declined significantly (p = 0.005; rate ratio, 0.71) from 1.9 in the pre-intervention period to 1.5 in the intervention period. Significant difference in VAP rates between these periods was found in the regional hospitals (from 1.6 to 0.7; p

Background/purpose: This study investigated the cause of hand hygiene deficit, and further implemented a quality improvement program using WHO's hand-hygiene strategy to enhance the compliance of hand hygiene in the nursing home in Taiwan. Methods: This prospective study was conducted in eleven nursing homes in Taiwan from January 2015 to December 2016. After intervention, we monitor the compliance, and accuracy of hand hygiene. In addition, we also calculated the number of episodes of infection per 1000 resident-days in each nursing home in the intervention period (July–December 2015) and post-intervention period (January–October 2016). Results: Overall, the consumption of alcohol-based handrubs increased from 10.1 ml per resident-day in intervention period to 12.2 ml per resident-day in post intervention period. The compliance of hand hygiene increased from 74% in intervention period to 79% in post-intervention period and the rate of correct hand hygiene increased from 81% in intervention period to 87% in post-intervention period. Most importantly, the infection density decreased from 2.39 per 1000 resident-day in intervention period to 1.89 per 1000 resident-day. Conclusions: A national quality-improvement program using WHO's hand-hygiene strategy to enhance hand hygiene and reduce healthcare associated infection is effective in nursing homes in Taiwan. Keywords: Quality improvement program, Hand hygiene, Nursing homes, Taiwan

Objectives: This study was intended to investigate the clinical and microbiological characteristics of patients with bacteremia caused by Campylobacter species. Methods: From April 1998 to May 2014, 56 adults with bacteremia caused by Campylobacter species were evaluated. These Campylobacter species isolates were confirmed to the species level using 16S rRNA gene sequencing (all isolates) and multiplex PCR analysis (for C. fetus only). The performance of identification for Campylobacter species by the Bruker Biotyper MALDI-TOF MS was evaluated. The genetic relatedness of C. fetus isolates was analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Results: The leading underlying medical conditions of these patients were malignancy (46.4%), hypertension (35.7%), and liver cirrhosis (23.2%). The overall 30-day mortality rate was 5.4%. Using 16S rRNA sequencing analysis, 26 isolates of C. coli, 11 of C. jejuni, and 19 of C. fetus, including 15 C. fetus subsp. fetus and five C. fetus subsp. venerealis, were identified. Among the five C. fetus subsp. venerealis isolates recognized by 16S rRNA gene sequencing, only two isolates were C. fetus subsp. venerealis by multiplex PCR method. The Bruker Biotyper MALDI-TOF MS failed to correctly identify C. fetus subsp. venerealis isolates. MLST analysis of C. fetus isolates revealed three STs: ST20 (n = 12), ST11 (n = 5), and ST57 (n = 2), which were compatible with three major PFGE clusters. Conclusion: Database expansion of MALDI-TOF MS for the correct identification of C. fetus to subspecies levels is needed. A novel clone of ST57-PFGE Cluster C of C. fetus subsp. venerealis was noted. Keywords: Campylobacter, Campylobacter fetus, API Campy system, Bruker Biotyper MALDI-TOF MS, 16S RNA gene sequencing, Multiplex PCR

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.

Background: The clinical impact of infection with Mycobacterium (M.) abscessus complex (MABC), a group of emerging non-tuberculosis mycobacteria (NTM), is increasing. M. abscessus subsp. abscessus/bolletii frequently shows natural resistance to macrolide antibiotics, whereas M. abscessus subsp. massiliense is generally susceptible. Therefore, rapid and accurate discrimination of macrolide-susceptible MABC subgroups is required for effective clinical decisions about macrolide treatments for MABC infection. We aimed to develop a simple and rapid diagnostic that can identify MABC isolates showing macrolide susceptibility. Methods: Whole genome sequencing (WGS) was performed for 148 clinical or environmental MABC isolates from Japan to identify genetic markers that can discriminate three MABC subspecies and the macrolide-susceptible erm(41) T28C sequevar. Using the identified genetic markers, we established PCR based- or DNA chromatography-based assays. Validation testing was performed using MABC isolates from Taiwan. Finding: We identified unique sequence regions that could be used to differentiate the three subspecies. Our WGS-based phylogenetic analysis indicated that M. abscessus carrying the macrolide-susceptible erm(41) T28C sequevar were tightly clustered, and identified 11 genes that were significantly associated with the lineage for use as genetic markers. To detect these genetic markers and the erm(41) locus, we developed a DNA chromatography method that identified three subspecies, the erm(41) T28C sequevar and intact erm(41) for MABC in a single assay within one hour. The agreement rate between the DNA chromatography-based and WGS-based identification was 99·7%. Interpretation: We developed a novel, rapid and simple DNA chromatography method for identification of MABC macrolide susceptibility with high accuracy. Funding: AMED, JSPS KAKENHI

Background Mycobacterium 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. Methods We performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010–2017 at seven hospitals across Taiwan. Results In 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%. Conclusions The 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.

Patients with immune-mediated inflammatory diseases (IMID) were seldom enrolled in the studies of SARS-CoV-2 vaccines, and real-world data regarding the immunogenicity of different types of vaccines is limited. We aimed to assess the immunogenicity and safety of three types of vaccines (AZD1222, mRNA-1273, and BNT162b2) in 253 patients with IMID and 30 healthcare workers (HCWs). Plasma levels of IgG-antibody against SARS-CoV-2 targeting the receptor-binding domain of spike protein (anti-S/RBD-IgG) were determined by chemiluminescent immunoassay 3–4 weeks after the first-dose and second-dose vaccination. The positive rate and titers of anti-S/RBD-IgG were significantly higher in mRNA-1273 or BNT162b2 than in the AZD1222 vaccine. Immunogenicity was augmented after the second dose of any vaccine type in all IMID patients, suggesting that these patients should complete the vaccination series. Anti-S/RBD-IgG titers after first-dose vaccination were significantly lower in RA patients than pSS patients, but there was no significant difference after second-dose vaccination among five groups of IMID patients. The positive rate and titers of anti-S/RBD-IgG were significantly lower in patients receiving abatacept/rituximab therapy than in those receiving other DMARDs. All three SARS-CoV-2 vaccines showed acceptable safety profiles, and the common AEs were injection site reactions. We identified SLE as a significant predictor of increased autoimmunity and would like to promote awareness of the possibility of autoimmunity following vaccination.

For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of COVID-19 are scarce and desperately needed to meet the clinical need. However, a trend could be observed based on current clinical evidence. Remdesivir and favipiravir may shorten the recovery time; lopinavir/ritonavir does not demonstrate treatment efficacy in severe patients. Triple therapy of ribavirin, lopinavir, and interferon β-1b showed early viral negative conversion, and the major effect may be related to interferon. Some small sample-size studies showed that interleukin-6 inhibitors may demonstrate clinical improvement; non-critical patients may benefit from convalescent plasma infusion in small sample-size studies; and the role of hydroxychloroquine or chloroquine in the treatment and prophylaxis of COVID-19 remains unclear. Combination therapy of traditional Chinese medicine with antiviral agents (ex. interferon, lopinavir, or arbidol) may alleviate inflammation in severe COVID-19 patients based on small sample-sized observational studies and experts’ opinion. Most of the published studies included severe or critical patients with COVID-19. Combination therapy of antiviral agents and immune-modulating drugs is reasonable especially for those critical COVID-19 patients with cytokine release syndrome. Drugs to blunt cytokine release might not benefit for patients in the early stage with mild disease or the late stage with critical illness. Traditional Chinese medicine with antiviral effects on SARS-CoV-2 and immune-modulation is widely used for COVID-19 patients in China, and is worthy of further studies. In this review, we aim to highlight the available therapeutic options for COVID-19 based on current clinical evidence and encourage clinical trials specific for children and for patients with mild disease or at the early stage of COVID-19.

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.

From January 2013 to December 2018, 90 Escherichia coli isolates were collected from 90 sick pigs on 58 farms in seven cities in Taiwan. The minimum inhibitory concentrations (MICs) of the isolates to 14 antimicrobial agents were determined on the VITEK 2 system (bioMérieux, Marcy-l’Etoile, France), and the resistance to colistin was assessed via the reference broth microdilution (BMD) method. The mobilized colistin resistance genes (mcr) were determined for the colistin-resistant isolates, which displayed BMD MICs ≥ 4 mg/L. Genotypes of the mcr-positive E. coli isolates were determined by multilocus sequence typing, arbitrarily primed polymerase chain reaction (PCR), and pulsed-field gel electrophoresis. All of the isolates were tested for susceptibility to carbapenems. Fifty isolates (55.6%) were resistant to colistin, 39 of which (78%) were positive for the mcr-1 gene. E. coli isolates harboring mcr-1 were most frequent in 2017 (15/18, 83.3%), followed by 2018 (13/23, 56.5%), 2015 (7/21, 33.3%), and 2016 (3/24, 12.5%). A total of 18 sequence types (STs) were identified among the 39 porcine mcr-1-carrying E. coli isolates; 13 were ST2521 (33.3%) isolated in 2017 and 2018. Five genotypes (clones) were identified, and the same genotypes were in sick pigs on the same farm and different farms. This suggests intra- and inter-farm spread of porcine mcr-1-carrying E. coli. The results presented here indicate high colistin resistance and wide mcr-1 E. coli prevalence among the sick pigs sampled in 2015–2018 in different regions of Taiwan.

BACKGROUND:Undiagnosed tuberculosis (TB) patients hospitalized because of comorbidities constitute a challenge to TB control in hospitals. We aimed to assess the impact of introducing highly sensitive fluorescent microscopy for examining sputum smear to replace conventional microscopy under a high TB risk setting. METHODS:We measured the impact of switch to fluorescent microscopy on the smear detection rate of culture-confirmed pulmonary TB, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately 400 TB cases annually) in Taipei. Multivariable Cox regression was applied to adjust for effects of covariates. The effect attributable to the improved smear detection rate was determined using causal mediation analysis. RESULTS:After switch to fluorescence microscopy, median non-isolated infectious duration decreased from 12.5 days to 3 days (P

Background: Vascular infections (VI) are potentially catastrophic complications of nontyphoid Salmonella (NTS). We aimed to develop a scoring model incorporating information from blood culture time to positivity (TTP-NTSVI) and compared the prediction capability for VI among adults with NTS bacteremia between TTP-NTSVI and a previously published score (Chen-NTSVI). Methods: This retrospective cohort study enrolled 217 adults with NTS bacteremia ≧ 50 years old. We developed a TTP-NTSVI score by multiple logistic regression modeling to identify independent predictors for imaging-confirmed VI and assigned a point value weighting by the corresponding natural logarithm of the odds ratio for each model predictor. Chen-NTSVI score includes hypertension, male sex, serogroup C1, coronary arterial disease (CAD) as positive predictors, and malignancy and immunosuppressive therapy as negative predictors. The prediction capability of the two scores was compared by area under the receiver operating characteristic curve (AUC). Results: The mean age was 68.3 ± 11.2 years-old. Serogroup D was the predominant isolate (155/217, 71.4%). Seventeen (7.8%) patients had VI. Four independent predictors for VI were identified: male sex (24.9 [2.59–239.60]; 6) (odds ratio [95% confidence interval]; assigned score point), peripheral arterial occlusive disease (9.41 [2.21–40.02]; 4), CAD (4.0 [1.16–13.86]; 3), and TTP

Background/purpose: This study assessed the effect of the central line bundle on the rate of central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) in Taiwan. Methods: This national study was conducted in 27 ICUs with 404 beds total, including 15 medical ICUs, 11 surgical ICUs, and one mixed ICU. The study period was divided into two phases: a pre-intervention (between June 1, 2011 and October 31, 2011) and intervention phase (between December 1, 2011 and October 31, 2012). Outcome variables, including CLABSI rates (per 1000 catheter-days) and catheter utilization rates, were measured. Results: The overall rate of CLABSI significantly decreased by 12.2% (p

Background/purpose: Pyogenic liver abscess (PLA) and bacteremia caused by Klebsiella pneumoniae is a common complication among patients with diabetes mellitus (DM). The aim of this study is to investigate the prevalence of rectal carriage and serotype distribution of K. pneumoniae amongst DM patients and their clinical relevance. Methods: We prospectively collected rectal swabs for K. pneumoniae culture in asymptomatic DM patients from March 2008 to June 2009. Seven capsular serotypes that were commonly associated with PLA were determined by capsular polysaccharide synthesis (cps) genotyping. Microbiologically confirmed bacterial infections were evaluated 1 and 5 years after initial enrolment of the patients. Results: A total of 100 male and 62 female patients (mean age, 56.6 years) were enrolled. Of these, 77 (47.5%) had rectal K. pneumoniae colonization. Colonizers were older than non-colonizers (p = 0.03). Sex, fasting blood glucose, and initial HbA1C were not statistically different (p = 0.26, 0.18, and 0.31, respectively). Among the 65 available isolates, 22 (33.8%) belonged to the seven main serotypes. During the 5-year's follow-up, 21 patients developed microbiologically documented bacterial infections but none of them developed PLA and bacteremia. Risk factors for bacterial infection within 5 years included initial glycosylated hemoglobin (HbA1C) > 10% or first-year average HbA1C > 10%. Conclusion: Although nearly half of asymptomatic DM patients had rectal carriage of K. pneumoniae and one-third of them colonized by isolates belonging to the seven serotypes related to PLA, none of them subsequently developed PLA and colonized patients did not have higher risk of microbiologically confirmed bacterial infections. Keywords: Klebsiella pneumoniae, Pyogenic liver abscess, Diabetes mellitus, Bacterial infections, Rectal carriage

Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan. Keywords: Candida auris, Laboratory, Identification, Epidemiology, Taiwan

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.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used in the field of clinical microbiology since 2010. Compared with the traditional technique of biochemical identification, MALDI-TOF MS has many advantages, including convenience, speed, accuracy, and low cost. The accuracy and speed of identification using MALDI-TOF MS have been increasing with the development of sample preparation, database enrichment, and algorithm optimization. MALDI-TOF MS has shown promising results in identifying cultured colonies and rapidly detecting samples. MALDI-TOF MS has critical research applications for the rapid detection of highly virulent and drug-resistant pathogens. Here we present a scientific review that evaluates the performance of MALDI-TOF MS in identifying clinical pathogenic microorganisms. MALDI-TOF MS is a promising tool in identifying clinical microorganisms, although some aspects still require improvement.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus in humans, has expanded globally over the past year. COVID-19 remains an important subject of intensive research owing to its huge impact on economic and public health globally. Based on historical archives, the first coronavirus-related disease recorded was possibly animal-related, a case of feline infectious peritonitis described as early as 1912. Despite over a century of documented coronaviruses in animals, the global animal industry still suffers from outbreaks. Knowledge and experience handling animal coronaviruses provide a valuable tool to complement our understanding of the ongoing COVID-19 pandemic. In this review, we present an overview of coronaviruses, clinical signs, COVID-19 in animals, genome organization and recombination, immunopathogenesis, transmission, viral shedding, diagnosis, treatment, and prevention. By drawing parallels between COVID-19 in animals and humans, we provide perspectives on the pathophysiological mechanisms by which coronaviruses cause diseases in both animals and humans, providing a critical basis for the development of effective vaccines and therapeutics against these deadly viruses.

Human infections with Campylobacter fetus are often assumed to be derived from livestock. Here, Iraola et al. provide evidence that healthy humans may act as carriers and dispersers, and C. fetus may have originated in humans as an intestinal pathobiont and then adapted as a livestock pathogen.

Background/Purpose: This prospective before-after study was intended to investigate the effect of Bio-Kil on reducing environmental bacterial burden and healthcare-associated infections (HAIs) in intensive care units (ICUs) at the Municipal Wan-Fang Hospital, Taipei, Taiwan in 2014. Methods: Four rooms in the medical and surgical ICUs were investigated and designated as study rooms (n = 2) or control rooms (n = 2). Routine disinfection was performed during the pre-intervention period in both room types. Bio-Kil was applied to the fomites and surroundings of the study rooms during the intervention period. Total bacterial burden and proportion of colonization of fomites and surroundings by multidrug-resistance organisms (MDROs) were determined before and after the intervention. The demographic characteristics, underlying conditions, and clinical outcomes of patients were analyzed. Results: After application of Bio-Kil, the bacterial burden declined in both groups, although the reduction was greater in the study rooms as compared with the control rooms (p = 0.001). During the pre-intervention period, 16 patients were admitted to control rooms and 18 patients to study rooms. After the intervention, 22 patients were admitted to control rooms and 21 patients to study rooms. The number of cases of new-onset sepsis declined in the intervention group (from 33% to 23.8%), but increased in the control group (from 25% to 40.9%); however, there was no significant difference in incidence of new-onset sepsis between the study and control rooms after intervention. Conclusion: Application of Bio-Kil reduced the environmental bacterial burden and MDROs in ICUs. Further studies are needed to evaluate the efficacy of this nanotechnology-based disinfectant in reducing HAIs.

Background/purpose: This study was intended to investigate the impact of implementation of catheter-associated urinary tract infection (CA-UTI) bundle care on the incidence of CA-UTI in high-risk units. Methods: Thirteen high-risk units, including medical (n = 5), surgical (n = 3), cardiac intensive care units (n = 2), respiratory care centers (n = 2), and respiratory care ward (n = 1) were included in this quality-improvement project. This study was divided into pre-intervention phase (from January 1 to July 31) and post-intervention phase (from August 1 to October 31) in 2013. Results: The incidence of CA-UTI decreased by 22.7%, from 3.86 to 2.98 per 1000 catheter-days (95% confidence interval, 0.65–0.82; p

Background/Purpose: The aim of this study was to investigate the cefoperazone–sulbactam (CFP–SUL) susceptibilities of important Gram-negative bacteria (GNB) by agar dilution (reference method), disk diffusion, and two automated methods. Methods: A total of 799 GNB isolates, including Enterobacteriaceae (n = 500) and nonfermentative GNB (NFGNB, n = 299), were recovered from various clinical specimens collected at National Taiwan University Hospital, Taipei, Taiwan from November 2013 to December 2014. The agar dilution method, disk diffusion method, and two automated susceptibility systems (Phoenix and Vitek 2) were used for testing susceptibility of the isolates to CFP–SUL. Categories of susceptibility (susceptible, intermediate, or resistant) to CFP–SUL yielded from each method were interpreted according to CFP–SUL interpretive breakpoints proposed previously. The results of categorical agreement and errors obtained between the agar dilution method and the other three methods were analyzed. Results: The Vitek 2 system had the highest error rates against Escherichia coli (n = 150) and Enterobacter cloacae (n = 77) isolates, i.e., 6.7% and 11.7% minor errors, 8.5% and 1.7% major errors, and 40% and 20% very major errors, respectively. Additionally, the Vitek 2 system was also found to have a significantly lower sensitivity (44.4%) and lower positive predictive value (18.2%) for detecting CFP–SUL nonsusceptible E. coli isolates than other methods. For carbapenem-nonsusceptible Enterobacteriaceae isolates, the Vitek 2 system failed to detect correct susceptibility to CFP–SUL. The three methods failed to correctly detect CFP–SUL susceptibility categories against all NFGNB isolates except Pseudomonas aeruginosa. Conclusion: The Vitek 2 system is a suboptimal method in correctly detecting CFP–SUL susceptibility categories for E. coli, E. cloacae, and carbapenem-nonsusceptible Enterobacteriaceae isolates.

Background/Purpose: For extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae. Methods: Between 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint. Results: A total of 299 patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia score ≥ 4 points; odds ratio (OR), 7.09; p

Objectives: This study investigated the prevalence of multidrug-resistant organisms (MDROs) in the residents and environments of long-term care facilities (LTCFs) in Taiwan. Methods: We prospectively investigated the distribution of MDROs in residents of six LTCFs and their environments from January 2015 to December 2015 (intervention period). Active surveillance of colonization of MDROs was performed by culturing rectal and nasal swab samples every 3 months for the residents: 63, 79, and 73 in the first, second, and third surveillance investigations, respectively. If MDROs, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa, and MDR Acinetobacter baumannii were identified, then swab specimens from environmental sources were also collected and cultured. During the study period, several infection control measures were also implemented. Results: The overall infection density decreased significantly from 2.69 per 1000 patient–days in the preintervention (January 2014 to December 2014) to 2.39 per 1000 patient–days during the intervention period (p

Nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm for infectious diseases. Infections caused by multidrug-resistant organisms (MDROs) are emerging as causes of morbidity and mortality worldwide. Antibiotic options for infections caused by MDROs are often limited. These clinical challenges highlight the critical demand for alternative and effective antimicrobial strategies. Nanoparticles (NPs) can penetrate the cell membrane of pathogenic microorganisms and interfere with important molecular pathways, formulating unique antimicrobial mechanisms. In combination with optimal antibiotics, NPs have demonstrated synergy and may aid in limiting the global crisis of emerging bacterial resistance. In this review, we summarized current research on the broad classification of the NPs that have shown in vitro antimicrobial activity against MDROs, including the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The pharmacokinetics and pharmacodynamic characteristics of NPs and bacteria-resistant mechanisms to NPs were also discussed.

Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new β-lactam/β-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE.