Trends in susceptibility of vancomycin-resistant Enterococcus faecium to tigecycline, daptomycin, and linezolid and molecular epidemiology of the isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006 to 2010.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC(90)s) from 2006-2007 (0.06 µg/ml) to 2008-2010 (0.12 µg/ml). The MIC(90)s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

Cutaneous infection caused by Gordonia amicalis after a traumatic injury.

Gordonia amicalis infection has never been reported in humans. We report here the first case of G. amicalis-related cutaneous infection after a traumatic injury. The isolate was confirmed by 16S rRNA sequencing analysis, and the patient responded well to repeated debridement and antibiotic treatment.

Recurrent bacteremia caused by the Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

This study investigated the clinical and microbiological characteristics of patients with recurrent bacteremia caused by the Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex at a medical center. All ACB complex isolates associated with recurrent bacteremia were identified to the genomic species level using a 16S-23S rRNA gene intergenic spacer sequence-based method. Genotypes were determined by the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR and by pulsotypes generated by pulsed-field gel electrophoresis. Relapse of infection was defined as when the genotype of the recurrent isolate was identical to that of the original infecting strain. Reinfection was defined as when the genospecies or genotype of the recurrent isolate differed from that of the original isolate. From 2006 to 2008, 446 patients had ACB complex bacteremia and 25 (5.6%) had recurrent bacteremia caused by the ACB complex. Among the 25 patients, 12 (48%) had relapse of bacteremia caused by A. nosocomialis (n = 7) or A. baumannii (n = 5). Among the 13 patients with reinfection, 5 (38.5%) had reinfection caused by different genospecies of the ACB complex. Most of the patients were immunocompromised, and most of the infection foci were catheter-related bloodstream infections. The overall in-hospital mortality rate was 33.3%. A. baumannii isolates had lower antimicrobial susceptibility rates than A. nosocomialis and A. pittii isolates. In conclusion, relapse of ACB complex bacteremia can develop in immunocompromised patients, especially those with central venous catheters. Molecular methods to identify the ACB complex to the genospecies level are essential for differentiating between reinfection and relapse of bacteremia caused by the ACB complex.

Otitis media and otomastoiditis caused by Mycobacterium massiliense (Mycobacterium abscessus subsp. bolletii).

We describe two patients with otologic infections caused by Mycobacterium massiliense (M. abscessus subsp. bolletti) which were identified using erm(41) PCR, 23S rRNA, and rpoB gene sequence analysis. They were middle-aged adults with underlying otologic diseases and were treated successfully with clarithromycin-based combination regimens for 3 and 9 months, respectively.

Control of an outbreak of COVID-19 at a tertiary hospital in Taiwan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has circulated in Taiwan since late 2019. Healthcare facilities are vulnerable to COVID-19 outbreaks due to clusters of symptomatic patients and susceptible hosts. Prompt control of outbreaks is crucial. In May 2021, an index case of COVID-19 was detected at Far Eastern Memorial Hospital (FEMH) in New Taipei City, Taiwan, 3 days after hospital admission, spreading to 26 patients and staff. Herein we evaluate control of this COVID-1 outbreak. METHODS: To control the outbreak, the index case ward was closed, and large-scale COVID-19 testing (RT PCR) was performed for all inpatients, caregivers and healthcare workers (HCWs). All exposed persons were quarantined. Thorough investigation was conducted to analyze the transmission route. RESULTS: The outbreak comprised 12 patients, 12 caregivers, and 3 HCWs. Seven patients expired and the remaining cases recovered. Overall, 456 patients/caregivers and 169 HCWs were quarantined. Analysis showed that longer exposure time was the main cause of HCW infection; all three infected HCWs were primary-care nurses related to the index case. To diminish hidden cases, all hospitalized patients/caregivers received PCR examinations and all results were negative. Thereafter, all patients/caregivers routinely received PCR examination on admission. Hospital-wide PCR screening for HCW detected 4 positive HCWs unrelated to this outbreak, and a second-round of screening detected 2 more cases, with no additional cases during the following 6 months. CONCLUSION: Prompt infection control measures and large-scale PCR screening can control a COVID-19 outbreak within 2 weeks. Exposure time is the major risk factor for HCW infection.

Antimicrobial susceptibility of bacteremic vancomycin-resistant Enterococcus faecium to eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics: Results from the 2019-2020 Nationwide Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan.

Fatal pneumonia and empyema thoracis caused by imipenem-resistant Nocardia abscessus in a cancer patient.

We describe a case of pneumonia and empyema thoracis caused by trimethoprim-sulfamethoxazole-susceptible, but imipenem-resistant Nocardia abscessus in a cancer patient. The isolate was confirmed to the species level by 16S rRNA sequencing analysis. The patient did not respond to antibiotic therapy, including ceftriaxone and imipenem, and died of progressing pneumonia and multiple organ failure.

Disease Burden of Invasive Listeriosis and Molecular Characterization of Clinical Isolates in Taiwan, 2000-2013.

The information about disease burden and epidemiology of invasive listeriosis in Asia is scarce. From 2000 to 2013, a total of 338 patients with invasive listeriosis (bacteremia, meningitis, and peritonitis) were treated at four medical centers in Taiwan. The incidence (per 10,000 admissions) of invasive listeriosis increased significantly during the 14-year period among the four centers (0.15 in 2000 and >1.25 during 2010-2012) and at each of the four medical centers. Among these patients, 45.9% were elderly (>65 years old) and 3.3% were less than one year of age. More than one-third (36.7%) of the patients acquired invasive listeriosis in the spring (April to June). Among the 132 preserved Listeria monocytogenes isolates analyzed, the most frequently isolated PCR serogroup-sequence type (ST) was IIb-ST87 (23.5%), followed by IIa-ST378 (19.7%) and IIa-ST155 (12.1%). Isolation of PCR serogroups IIb and IVb increased significantly with year, with a predominance of IIb-ST87 isolates (23.5%) and IIb-ST 228 isolates emerging in 2013. A total of 12 different randomly amplified polymorphic DNA (RAPD) patterns (Patterns I to XII) were identified among the 112 L. monocytogenes isolates belonging to eight main PCR serogroup-STs. Identical RAPD patterns were found among the isolates exhibiting the same PCR serogroup-ST. In conclusion, our study revealed that during 2000-2013, listeriosis at four medical centers in Taiwan was caused by heterogeneous strains and that the upsurge in incidence beginning in 2005 was caused by at least two predominant clones.

Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by extended-spectrum ß-lactamase-producing Proteus mirabilis.

This study was intended to delineate the role of carbapenems and piperacillin/tazobactam in treating bacteremia caused by extended-spectrum ß-lactamase (ESBL)-producing Proteus mirabilis. We performed a multicenter and retrospective study of the patients with ESBL-producing P. mirabilis bacteremia. The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem for at least 48 hours and the MICs of the prescribed drugs for these isolates were analyzed. Forty-seven patients with available clinical data were included. The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to imipenem. Among the 3 patients infected with isolates exhibiting non-susceptibility to imipenem (MIC ≥2 mg/L) who were treated with imipenem, none died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital (19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However, among those treated by piperacillin/tazobactam, the mortality rate of those infected by the isolates with lower piperacillin/tazobactam MICs (≤0.5/4 mg/L) was lower than that of the isolates with MICs of ≥1/4 mg/L (0%, 0/7 versus 60%, 3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with significant mortality, and carbapenem therapy could be regarded as the drugs of choice. The role of piperacillin/tazobactam, especially for the infections due to the isolates with an MIC ≤0.5/4 mg/L, warrants more clinical studies.

Catheter-related fungemia caused by Candida dubliniensis.

Infections caused by Candida dubliniensis in humans are rare and have never been reported in Taiwan. We report two cancer patients with catheter-related fungemia due to C. dubliniensis infection in Taiwan. The two isolates were confirmed to the species level using an oligonucleotide array system and sequence analysis, and both showed high in vitro susceptibilities to nine antifungal agents. The catheters were removed, and both patients responded well to antifungal treatment. Although this type of infection is rare, physicians should consider C. dubliniensis as one of the possible pathogens causing catheter-related infections in Taiwan.

Bacteremia caused by Pantoea agglomerans at a medical center in Taiwan, 2000-2010.

BACKGROUND/PURPOSE: There are only three case reports of adult patients with spontaneous Pantoea agglomerans bacteremia in the English literature. The aim of this study was to investigate clinical and microbiologic characteristics patients of P agglomerans bacteremia. METHODS: We studied all adult patients with P agglomerans bacteremia at a medical center from 2000 to 2010. The isolates were identified using two commercial identification systems. RESULTS: Of the 18 patients identified, 72% (n = 13) had active gastroesophageal disease treated with antacids. Two-thirds of patients had indwelling central lines and advanced cancers. None of the removed catheter tips yielded P agglomerans and line persistence was not associated with adverse outcomes. Initial disease severity was low, hypotension was uncommon and no patient died of bacteremia. Recurrence of bacteremia occurred in one patient with deep-seated infection. 16srRNA gene sequencing identified only half of the isolates as P agglomerans. The remaining nine isolates were Enterobacter species for six, Pantoea ananatis for two, and Exiguobacterium profundum for one. There were no significant differences between the characteristics of the subgroup molecularly identified as P agglomernas and the overall group characteristics. Eleven (61%) of the 18 isolates were susceptible to cefazolin, six (33%) susceptible to fosfomycin (MIC ≤ 64 mg/ml). Two isolates had colistin MICs ≥ 4 mg/ml. CONCLUSION: Bacteremia caused by P agglomerans is associated with gastroesophageal reflux disease and receipt of antacids. 16srRNA gene sequencing should not be used as the sole basis for its identification and we have highlighted the need for another molecular-based technique to conclusively characterize P agglomerans.

Updated antibiotic resistance and clinical spectrum of infections caused by Streptococcus pneumoniae in Taiwan: Emphasis on risk factors for penicillin nonsusceptibilities.

BACKGROUND/PURPOSE(S): Streptococcus pneumoniae is one of the leading pathogens causing community-acquired infection with high mortality rates in elderly patients. Emerging antibiotic resistance was found in past decades. Continuous surveillance to monitor changes in antibiotic resistance of S. pneumoniae and associated risk factors are important clinical issues. METHODS: Isolates of S. pneumoniae collected from six hospitals participating in the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program III (2002) - VI (2008) were enrolled in this study. Bacterial susceptibilities were determined by minimum inhibitory concentration. The clinical data of source patients were collected retrospectively. RESULTS: A total of 330 nonduplicate S. pneumoniae isolates were enrolled in this study. Sputum was the most common specimen source, followed by pus. The mean age of the source patients was 38 years among these 330 patients, and 247 had various infections caused by S. pneumoniae. The overall in-hospital mortality rate was 6% and most (60%)of the mortality occurred in patients older than 65 years. The mortality rates among the patients age 65 years and older and those age 5 years and younger were 12.9% (9 of 70) and 2.4% (2 of 83), respectively. The rates of nonsusceptibility to penicillin by the meningitis criteria (PNSP-M) were 69.0% in 2002, 81.0% in 2004, 73.7% in 2006, and 74.5% in 2008. Resistance to erythromycin and trimethoprim/sulfamethoxazole remained high. Using multivariate analysis, patients with PNSP isolates were more likely to have a history of antibiotic exposure within the previous 15 days compared with patients with penicillin-susceptible (PSSP) isolates (nonmeningitis criteria: 29.70% vs. 18.34%, p = 0.0288; meningitis criteria: 25.30% vs. 9.88%, p = 0.006). Shock at presentation was the risk factor for in-hospital mortality. CONCLUSION: Our study demonstrated that the rates of penicillin nonsusceptibility among S. pneumoniae remained high in Taiwan during the study period. Previous antibiotic exposure was the only risk factor for subsequent acquisition of penicillin- nonsusceptible S. pneumoniae compared with penicillin-susceptible S. pneumoniae. Judicious antibiotic use is important to control the spread of drug nonsusceptible S. pneumoniae.

A Phase I, randomized, open-label study to evaluate the safety and immunogenicity of an enterovirus 71 vaccine.

BACKGROUND: Large-scale outbreaks of enterovirus 71 (EV71) infections have occurred in Asia-Pacific regions. Severe complications include encephalitis and poliomyelitis-like paralysis, cardiopulmonary collapse, and death, necessitating an effective vaccine against EV71. METHODS: In this randomized Phase I study, we evaluated the safety and immunogenicity of an inactivated alum-adjuvanted EV71 whole-virus vaccine produced on Vero cell cultures. Sixty healthy volunteers aged 20-60 years received two doses of vaccine, administered 21 days apart. Each dose contained either 5 µg of EV71 antigen with 150 µg of adjuvant (Group A05) or 10 µg of EV71 antigen with 300 µg of adjuvant (Group B10). Serologic analysis was performed at baseline, day 21, and day 42. RESULTS: There were no serious adverse events. Mild injection site pain and myalgia were the most common adverse events with either vaccine formulation. The immunogenicity data showed that 90% of vaccine recipients have a 4-fold or greater increase in neutralization antibody titers (NT) after the first dose, without a further increase in NT after the second dose. The seroconversion rates on day 21 and day 42 were 86.7% and 93.1% respectively, in Group A05, and 92.9% and 96.3%, respectively, in Group B10. Thus, 5 µg and 10 µg of the EV71 vaccine can induce a remarkable immune response in healthy adults after only the first vaccination. CONCLUSION: The 5 µg and 10 µg adjuvanted EV71 vaccines are generally safe and immunogenic in healthy adults. (ClinicalTrials.gov number, NCT01268787).

Trends in the antimicrobial susceptibilities and serotypes of Streptococcus pneumoniae: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.

Isolates of Streptococcus pneumoniae (n = 530) were collected from 20 hospitals in different parts of Taiwan from 2006 to 2010. MICs to 16 antimicrobial agents were determined by broth dilution method and serotypes were identified by latex agglutination. Based on meningitis (non-meningitis) criteria established by the CLSI, 11.7% (63.2%) of all isolates were susceptible to penicillin and 46.0% (83.8%) were susceptible to ceftriaxone. Of the isolates, 94.3% were non-susceptible to azithromycin and 5.8% and 7.2% were non-susceptible to moxifloxacin and levofloxacin, respectively. Susceptibility to penicillin by meningitis criteria increased significantly (P = 0.0012) with year, and that to clindamycin and amoxicillin/clavulanic acid declined significantly (P < 0.05). Six major serotypes were found, namely 19F (24.0%), 23F (18.5%), 14 (13.6%), 6B (12.5%), 19A (7.5%) and 3 (5.1%). Prevalence of serotypes 19F and 14 remained stationary, that of serotype 6B decreased significantly (P < 0.0001) and that of serotype 19A increased significantly (P < 0.0001) with year. The coverage rate of PCV-7 among the pneumococcal isolates declined from 80.5% in 2006 to 50% in 2010 (P < 0.0001) and that of PCV-13 declined from 91.5% in 2009 to 75% in 2010. The non-susceptibility rate to levofloxacin was highest among serotype 23F isolates (13.3%) and lowest among serotype 19A isolates (2.5%). Rates of resistance to the four agents penicillin, ceftriaxone, azithromycin and clindamycin were highest among serotype 19A isolates (70.0%) and 23F isolates (49.0%). All serotype 3 isolates were susceptible to four of the most commonly used antibiotics (penicillin, ceftriaxone, azithromycin and levofloxacin).

Streptococcus suis infection in Taiwan, 2000-2011.

From 2000 to 2011, 8 patients with Streptococcus suis infections were identified in Taiwan. Six isolates were initially misidentified as Streptococcus acidominimus using commercial identification systems and later confirmed to be S. suis using 16S rRNA gene sequencing analysis. Among the 7 isolates available for further analysis, all belonged to biotype II. Three serotype I isolates possessed the same genotypes, indicating the possible clonal spread of S. suis. All of these patients survived. S. suis infection is underestimated in Taiwan.

Association between incidence of candidaemia and consumption of antifungal agents at a medical centre in Taiwan.

This study investigated the correlations between consumption of antifungal agents and species distribution in candidaemia. The incidence of patients with community-acquired candidaemia (CAC) (per 1000 admissions) and healthcare-associated candidaemia (HCAC) (per 1000 admissions) as well as data on annual consumption [defined daily doses (DDD)/1000 patient-days] of various antifungal agents at a medical centre in Taiwan from 2000 to 2010 were evaluated. A total of 2682 episodes of candidaemia were identified, including 2468 HCAC (92.0%) and 214 CAC (8.0%). The most prevalent species was Candida albicans (53.3%), followed by Candida tropicalis (20.5%), Candida glabrata (15.4%), Candida parapsilosis (14.1%), Candida guilliermondii (1.7%) and Candida krusei (1.5%). The overall incidence of candidaemia remained stable, whereas that of candidaemia due to C. parapsilosis and C. guilliermondii decreased significantly with time. Significant negative correlations were found between the use of echinocandins and voriconazole and the incidence of C. parapsilosis candidaemia and between the use of caspofungin and the incidence of C. guilliermondii candidaemia. In contrast, there were significant positive correlations between the use of echinocandins and the incidence of C. tropicalis candidaemia, the use of azoles and the incidence of C. glabrata and non-albicans Candida candidaemia, and the use of itraconazole and the incidence of C. parapsilosis and C. guilliermondii candidaemia. Increased use of fluconazole was associated with an increased incidence of HCAC due to non-albicans Candida spp. In conclusion, the impact of consumption of antifungal agents on the incidence of candidaemia caused by different Candida spp. varies and warrants further studies to confirm these findings.