Chun-Hsing Liao

Increasing Incidence of Nontuberculous Mycobacteria, Taiwan, 2000–2008

To assess the species distribution and epidemiologic trends of nontuberculous mycobacteria, we examined isolates from patients in Taiwan. During 2000–2008, the proportion increased significantly from 32.3% to 49.8%. Associated disease incidence increased from 2.7 to 10.2 cases per 100,000 patients. Mycobacterium avium complex and M. abscessus were most frequently isolated.

Increasing trends in antimicrobial resistance among clinically important anaerobes and Bacteroides fragilis isolates causing nosocomial infections: emerging resistance to carbapenems.

ABSTRACT This study reports data on the susceptibilities to five commonly used antianaerobic agents of five clinically frequently encountered anaerobes from 2000 to 2007 and to Bacteroides fragilis isolates causing nosocomial infections from 1990 to 2006. There was a trend of decreasing susceptibilities of these anaerobes to ampicillin-sulbactam, cefmetazole, chloramphenicol, and clindamycin with time during the study period. The rates of susceptibility to clindamycin and cefmetazole for all clinical isolates of Bacteroides fragilis isolates were higher than those of isolates associated with nosocomial infections. The MICs of 207 anaerobic blood isolates collected in 2006 to 14 antimicrobial agents were determined by the agar dilution method. The rates of nonsusceptibility to imipenem and meropenem were 7% and 12% for B. fragilis isolates (n = 60), 7% and 3% for Bacteroides thetaiotamicron isolates (n = 30), 4% and 4% for Fusobacterium species (n = 27), 6% and 0% for Prevotella species (n = 16), 15% and 0% for Clostridium species (n = 28), and 0% and 0% for Peptostreptococcus species (n = 32). The rates of susceptibility to moxifloxacin were 90% for B. fragilis isolates, 87% for B. thetaiotaomicron isolates, 81% for Fusobacterium species, 75% for Prevotella species, 93% for Clostridium species, and 78% for Peptostreptococcus species. Thirty-six percent of Clostridium species and 12% of Peptostreptococcus species were not susceptible to metronidazole. Comparison of the data with the data from a previous survey from the same institute in 2002 revealed higher rates of nonsusceptibility to carbapenems, especially for B. fragilis, Fusobacterium species, and Prevotella species isolates. The high rates of nonsusceptibility to commonly used antianaerobic agents mandate our attention, and periodic monitoring of the trend of the resistance is crucial.

National survey of invasive pneumococcal diseases in Taiwan under partial PCV7 vaccination in 2007: emergence of serotype 19A with high invasive potential.

We conducted an active, population-based laboratory surveillance study to evaluate the epidemiologic features of invasive pneumococcal disease (IPD) in Taiwan. Concurrently, nasopharyngeal colonization of Streptococcus pneumoniae was evaluated among 1128 healthy children aged <or=5 years. The overall incidence was highest among children aged 2-4 years (15.6/100,000). Serotype 19A, which had never been reported in Taiwan previously, caused a substantial fraction of the invasive diseases (OR, 9.6; 95% CI, 3.1-29.4) among children aged 2-4 years. Comparing serotype distributions of the isolates from nasopharyngeal colonization among children aged <or=5 years, serotypes 14 (OR, 17.3; 95% CI, 5.2-57.9) and 19A (OR, 14.9; 95% CI, 1.9-117) had the highest invasive potential. The study found that serotype 19A expanded in Taiwan, a country with a low 7-valent conjugate pneumococcal vaccine coverage. The 7-valent conjugate pneumococcal vaccines covered 73% of cases in children aged between 2 and 4 years, and 64.7% of cases in children aged <2 years. Among patients aged >or=65 years, the 23-valent pneumococcal polysaccharide vaccine covered 70.4% of cases. In the future, a broader pneumococcal vaccine is needed.

A multicenter study of risk factors and outcome of hospitalized patients with infections due to carbapenem-resistant Acinetobacter baumannii

BACKGROUND Risk factors and outcome in patients who acquire nosocomial infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) are rarely investigated. METHODS A multicenter retrospective study was conducted to analyze the clinical and microbiological data of patients with nosocomial infections due to A. baumannii in 10 hospitals around Taiwan from May 2004 to December 2006. Comparisons were made between patients with infections due to CRAB and patients with infections due to carbapenem-susceptible A. baumannii (CSAB). RESULTS One hundred and twenty-one patients carrying CRAB (infections, n=91) and 127 patients carrying CSAB (infections, n=97) were recruited for analysis. Compared with patients with CSAB infections, patients with CRAB infections had a longer duration of hospital stay before A. baumannii was isolated (median 48 vs. 21 days, p<0.001) and were more likely to have had exposure to a carbapenem (adjusted odds ratio (AOR) 2.57, 95% confidence interval (95% CI) 1.43-5.35; p=0.02) and an intensive care unit (ICU) stay (AOR 3.42, 95% CI 1.76-5.26; p=0.008). Risk factors associated with CRAB bacteremia included duration of hospital stay before onset of bacteremia (AOR 1.009 per 1-day longer, 95% CI 1.03-1.24; p=0.049), prior colonization with A. baumannii (AOR 3.27, 95% CI 1.99-5.93; p=0.002), and hospitalization in the ICU (AOR 6.12, 95% CI 1.58-13.68; p=0.009). Patients with CRAB bacteremia had a higher mortality rate than patients with CSAB bacteremia (46.0% vs. 28.3%, p=0.04). Multivariate analysis showed that carbapenem resistance (AOR 5.31, 95% CI 1.88-13.25; p=0.002), central venous catheterization (AOR 3.27, 95% CI 1.55-10.56; p=0.009), and ICU stay (AOR 2.56, 95% CI 1.15-8.85; p=0.04) were independent variables associated with mortality in patients with A. baumannii bacteremia. CONCLUSIONS Patients with CRAB infections have a higher mortality rate than those with CSAB infections. Longer hospital stay, colonization with A. baumannii, and admission to the ICU were associated with the development of CRAB bacteremia.

Acinetobacter baumannii and Acinetobacter genospecies 13TU and 3 bacteraemia: comparison of clinical features, prognostic factors and outcomes

OBJECTIVES To investigate the clinical impact of different genospecies of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB complex; A. baumannii, Acinetobacter gen. sp. 13TU and Acinetobacter gen. sp. 3) on the severity of bacteraemia. METHODS We retrospectively compared the clinical features and outcomes of patients with bacteraemia caused by A. baumannii, Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. The genospecies were identified using oligonucleotide array sequence analysis (interspacer sequence), and the clonality of Acinetobacter gen. sp. 13TU and 3 isolates was determined by PFGE analysis. RESULTS A total of 215 patients with bacteraemia due to ACB complex were evaluated. Among them, 117 (54.4%) had A. baumannii bacteraemia, 77 (35.8%) had Acinetobacter gen. sp. 13TU bacteraemia and 21 (9.8%) had Acinetobacter gen. sp. 3 bacteraemia. A. baumannii bacteraemia was associated with a higher 14 day mortality rate (P < 0.001), a higher 30 day mortality rate (P < 0.001) and a higher in-hospital mortality rate than bacteraemia due to Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. Independent prognostic factors for the 30 day mortality included the Charlson co-morbidity index (P < 0.001) and Pitt bacteraemia score (P < 0.001). Bloodstream infection caused by a multidrug-resistant A. baumannii isolate appeared to be associated with a poor outcome (P = 0.069). There was no clonal spread of Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3 during the study period. CONCLUSIONS Bacteraemia due to multidrug-resistant strains but not A. baumannii per se appears to be associated with poor outcome.

Prevalence of and Risk Factors for Colonization by Methicillin-Resistant Staphylococcus aureus among Adults in Community Settings in Taiwan

ABSTRACT In order to determine the prevalence of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) colonization among adults in community settings in Taiwan and identify its risk factors, we conducted the present study. For a 3-month period, we enrolled all adults who attended mandatory health examinations at three medical centers and signed the informed consent. Nasal swabs were taken for the isolation of S. aureus. For each MRSA isolate, we performed multilocus sequence typing, identification of the staphylococcal cassette chromosome mec, tests for the presence of the Panton-Valentine leukocidin gene, and tests for drug susceptibilities. Risk factors for MRSA colonization were determined. The results indicated that the MRSA colonization rate among adults in the community settings in Taiwan was 3.8% (119/3,098). Most MRSA isolates belonged to sequence type 59 (84.0%). Independent risk factors for MRSA colonization included the presence of household members less than 7 years old (P < 0.0001) and the use of antibiotics within the past year (P = 0.0031). Smoking appeared to be protective against MRSA colonization (P < 0.0001).

Detection of Circulating Galactomannan in Serum Samples for Diagnosis of Penicillium marneffei Infection and Cryptococcosis among Patients Infected with Human Immunodeficiency Virus

ABSTRACT Galactomannan (GM) is a heteropolysaccharide in the cell walls of most Aspergillus and Penicillium species. Cross-reactivity of Cryptococcus neoformans galactoxylomannan in an Aspergillus GM test has also been reported. In this study, we used a Platelia Aspergillus enzyme immunoassay kit (Bio-Rad) to test serum samples obtained from 48 human immunodeficiency virus (HIV)-infected patients (15 with penicilliosis [7 with fungemia alone, 4 with cavitary lung lesions alone, 3 with both fungemia and cavitary lung lesions, and 1 with disseminated disease], 22 with cryptococcosis [11 with fungemia alone, 5 with cavitary lung lesions, 3 with both, and 3 with meningitis alone], and 11 without any invasive fungal infection [control]) for GM levels. None of the patients had aspergillosis or concurrent use of piperacillin-tazobactam or amoxicillin-clavulanate. The median time between diagnosis of fungal infection and collection of serum samples was 0 days for penicilliosis and 1.5 days for cryptococcosis. Of patients with penicilliosis, cryptococcosis, and controls, 73.3%, 13.6%, and 9%, respectively, had GM optical density (OD) indices of >0.5 (P = 0.0001). GM OD indices were higher for penicilliosis (median OD index, 4.419; range, 0.158 to >20) than for cryptococcosis (median, 0.247; range, 0.112 to 3.849) cases (P < 0.001). Patients with fungemic penicilliosis had higher OD indices (median, 10.628; range, 0.401 to >20) than patients with nonfungemic penicilliosis (median, 0.378; range, 0.158 to 4.419) and patients with cryptococcemia (median, 0.231; range, 0.112 to 1.168) (P < 0.001). Of the 15 patients with cavitary lung lesions, those with penicilliosis had higher antigen levels (median OD index, 1.641; range, 0.247 to >20) than those with cryptococcosis (median, 0.227; range, 0.112 to 3.849) (P = 0.011). This study showed that the GM OD index was significantly elevated for HIV patients with penicilliosis. The use of the GM antigen assay may facilitate earlier diagnosis of Penicillium marneffei infection for HIV-infected patients in areas of endemicity.

Antimicrobial susceptibilities of commonly encountered bacterial isolates to fosfomycin determined by agar dilution and disk diffusion methods.

ABSTRACT We studied the antimicrobial activity of fosfomycin against 960 strains of commonly encountered bacteria associated with urinary tract infection using standard agar dilution and disk diffusion methods. Species studied included 3 common species of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia; methicillin-susceptible and -resistant Staphylococcus aureus; and vancomycin-susceptible and resistant Enterococcus faecalis and E. faecium. MICs and inhibition zone diameters were interpreted in accordance with both the currently recommended Clinical and Laboratory Standards Institute (CLSI) criteria for urinary tract isolates of Escherichia coli and Enterococcus faecalis and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria for Enterobacteriaceae. Tentative zone diameter interpretive criteria were developed for species not currently published by CLSI or EUCAST. Escherichia coli was uniformly susceptible to fosfomycin, as were most strains of Klebsiella pneumoniae and Enterobacter cloacae. A. baumannii was resistant to fosfomycin, while the prevalence of resistance in P. aeruginosa and S. maltophilia was greatly affected by the choice of MIC breakpoint. New tentative zone diameter criteria for K. pneumoniae, E. cloacae, S. aureus, and E. faecium were able to be set, providing some interim laboratory guidance for disk diffusion until further breakpoint evaluations are undertaken by CLSI and EUCAST.

Clinical and microbiological characteristics of Nocardiosis including those caused by emerging Nocardia species in Taiwan, 1998–2008

The genus of Nocardia is rapidly expanding and the species distribution varies with different geographical locations. We retrospectively reviewed the laboratory records of the bacteriology laboratory at National Taiwan University Hospital from January 1998 to June 2008 to identify patients with nocardiosis. During the study period, 164 isolates of Nocardia spp. were identified from 134 patients but only 113 patients had Nocardia infection. Nocardia brasiliensis (n = 54) was the most common pathogen, followed by N. asteroides (n = 36), N. farcinica (n = 7), N. flavorosea (n = 4), N. otitidiscaviarum (n = 3), N. nova (n = 3), N. beijingensis (n = 2) and one each of N. puris, N. jinanensis and N. takedensis. The major types of infection were cutaneous infection (56.6%), pulmonary infection (33.6%) and disseminated infection (7.1%). Eighty-eight patients received sulfonamide-containing antibiotic and eight of 100 patients with available data on outcomes died during the episode of nocardiosis. In conclusion, the clinical and microbiological manifestations of Nocardiosis vary with the different Nocardia species. Accurate identification of the species is crucial to make the diagnosis.

Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.

Objectives:Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. Design:Prospective, observational, multicenter study. Setting, Patients, and Interventions:Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. Measurements and Main Results:Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44–79 yr) and Sequential Organ Failure Assessment score of 9 (5–13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p = 0.105) and 69% versus 50% (p = 0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p = 0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61–29.78; p = 0.009). Conclusions:Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.