Kwok-Woon Yu

Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species.

BackgroundInvasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy.MethodsA retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei.ResultsThere were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC.ConclusionClinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC.

Clinical and microbiological characteristics of Chryseobacterium indologenes bacteremia.

BACKGROUND/PURPOSE Reports detailing bacteremia caused by Chryseobacterium indologenes remain limited, with most cases reported in Taiwan. The clinical significance of C. indologenes has not been fully established. This retrospective study investigated the clinical features and antimicrobial susceptibility of C. indologenes bacteremia. METHODS Patients with C. indologenes bacteremia were identified at a medical center/teaching hospital in northern Taiwan between January 1, 2004 and January 31, 2008. Clinical features and the antimicrobial susceptibilities of these patients were analyzed. RESULTS Sixteen isolates of C. indologenes from 16 episodes in 16 patients were identified, with all patients having underlying diseases. Two patients (12.5%) had polymicrobial bacteremia. The portal of bacteremia was not determined in most cases. Other clinical syndromes included catheter-related bacteremia, urinary tract infection and peritonitis. The majority of patients had undergone invasive procedures. Other associated conditions included immunosuppression, neutropenia and prolonged use of antibiotics. Only three patients were treated with appropriate antibiotics according to minimum inhibitory concentrations. The susceptibilities of isolates to trimethoprim-sulfamethoxazole (75.0%), levofloxacin (62.5%), piperacillin-tazobactam (50.0%), ciprofloxacin (43.75%) and cefepime (12.5%) were variable and the bacteremia-related mortality rate was 6.25%. CONCLUSION C. indologenes isolates are resistant to multiple antibiotics, with newer fluoroquinolones and trimethoprim-sulfamethoxazole possibly representing the most appropriate antimicrobial agents to treat infections caused by this pathogen. However, the pathogenicity and factors of virulence for C. indologenes remain unclear, with our study revealing favorable outcomes of C. indologenes bacteremia. Epidemiological surveillance of this organism in Taiwan and extensive worldwide surveillance programs are required.

Dissemination of multidrug-resistant Acinetobacter baumannii carrying BlaOxA-23 from hospitals in central Taiwan

BACKGROUND Imipenem-resistant Acinetobacter baumannii (IRAB) poses a great threat to healthcare systems. Production of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is the major mechanism for imipenem resistance. In this study, we found a high prevalence of IRAB carrying a gene encoding CHDL, bla(OxA-23), in central Taiwan and elucidated the molecular characteristics and possible mechanisms of the spread of these isolates. METHODS During 2007, we collected 291 nonrepetitive A baumannii isolates from 10 teaching hospitals in Taiwan. The antimicrobial susceptibility of the isolates was determined by agar dilution or Etest. The genes encoding carbapenemase and related structure were detected by polymerase chain reaction mapping and sequencing, and the clonal relationship of the isolates was analyzed by pulsed-field gel electrophoresis. Plasmid localization of bla(OxA-23) was determined by extraction of plasmid with commercial kit and Southern blot analysis. RESULTS Among 142 IRAB isolates, 30 harbored the bla(OxA-23). The prevalence of IRAB with bla(OxA-23) was highest in central Taiwan compared to other areas [24.8% (27/109) vs. 1.6% (3/182); p < 0.001]. These IRAB with bla(OxA-23) were also resistant to other antimicrobial agents, except colistin. The PCR methods showed the presence of bla(OxA-51) in all isolates. We could exclude clonal spreading due to the diversity of the pulsotype. The bla(OxA-23) gene was detected in the plasmids of 6 isolates. Tn2006 was present in 22 (73.3%) isolates, and Tn2008, in 6 other isolates (26.7%). Two strains had bla(oxa-23)-ΔATPase but lacked upstream ISAba1. CONCLUSION The high prevalence of bla(OxA-23)-harboring IRAB in central Taiwan might be attributed to the transposition event of Tn2006.

Clinical and microbiological analysis of Elizabethkingia meningoseptica bacteremia in adult patients in Taiwan.

A limited number of reports have documented bacteremia caused by Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) in adults. Most cases have occurred in Taiwan. This study investigated the clinical features and risk factors for mortality from E. meningoseptica bacteremia and the antimicrobial susceptibilities of the isolates. Patients with E. meningoseptica bacteremia were retrospectively analyzed at a medical center/teaching hospital in northern Taiwan over a 3-y period. We analyzed clinical features and outcomes of patients and antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results of the isolates. 28 patients had nosocomial bacteremia and 4 patients had healthcare associated bacteremia. The isolates exhibited variable susceptibilities to levofloxacin, ciprofloxacin, piperacillin-tazobactam, tigecycline, and trimethoprim-sulfamethoxazole. PFGE demonstrated that most isolates were epidemiologically unrelated. The 28-d mortality rate was 41%. Multivariate analysis indicated that shock and use of inappropriate antibiotics were independent risk factors for mortality. In conclusion, nosocomial bloodstream infection due to E. meningoseptica is an increasing problem in Taiwan. Our study indicates that patients with E. meningoseptica bacteremia face poor prognoses, with shock and use of inappropriate antibiotics as the main risk factors for mortality. Further clinical study is needed to establish the optimal therapy for E. meningoseptica bacteremia.

Gender differences in treatment outcomes of tuberculosis patients in Taiwan: a prospective observational study

Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50 ~ 60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12-3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.

Characteristics of pncA mutations in multidrug-resistant tuberculosis in Taiwan

BackgroundPyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis (MDRTB) treatment. However, the unreliable results obtained from traditional susceptibility testing limits its usefulness in clinical settings. The detection of pncA gene mutations is a potential surrogate of PZA susceptibility testing, especially in MDRTB isolates. The impact of genotypes of M. tuberculosis in pncA gene mutations also remains to be clarified.MethodsMDRTB isolates were collected from six hospitals in Taiwan from January 2007 to December 2009. pncA gene sequencing, pyrazinamidase activity testing, and spoligotyping were performed on all of the isolates. PZA susceptibility was determined by the BACTEC MGIT 960 PZA method. The sensitivity and specificity of pncA gene analysis were estimated based on the results of PZA susceptibility testing.ResultsA total of 66 MDRTB isolates, including 37 Beijing and 29 non-Beijing strains, were included for analysis. Among these isolates, 36 (54.5%) were PZA-resistant and 30 (45.5%) were PZA-susceptible. The PZA-resistant isolates were more likely to have concomitant resistance to ethambutol and streptomycin. Thirty-seven mutation types out of 30 isolates were identified in the pncA gene, and most of them were point mutations. The sensitivities of pncA gene sequencing for PZA susceptibility in overall isolates, Beijing and non-Beijing strains were 80.6%, 76.2%, and 86.7% respectively, and the specificities were 96.7%, 93.8%, and 100% respectively.ConclusionsMore than half of the MDRTB isolates in this study are PZA-resistant. Analysis of pncA gene mutations helped to identify PZA-susceptible MDRTB isolates, especially in non-Beijing strains.

Clostridium perfringens septicemia with massive hemolysis.

Massive hemolysis with acute renal failure occurred in a previously healthy 69-year-old patient as a complication of Clostridium perfringens septicemia secondary to gall bladder empyema. To our knowledge, this is one of the few patients with C. perfringens septicemia and massive intravascular hemolysis who survived the episode and regained a normal renal function.

Clinical characteristics, treatment and prognostic factors of candidal meningitis in a teaching hospital in Taiwan

The prognostic factors of candidal meningitis had rarely been studied owing to the rarity of this disease. We identified 17 patients with candidal meningitis at a teaching hospital in Taiwan over a 14-y period and give details of the clinical features, treatment, outcome and prognostic factors of this disease. 10 patients were children (1 was neonate) and 7 were adults. The clinical features and cerebrospinal fluid (CSF) findings were non-specific. The disease was diagnosed >72 h after hospitalization in 14 (82%) patients. The most frequently isolated species was Candida albicans (65%). Regimens of therapy included intravenous amphotericin B deoxycholate (AmB) or fluconazole alone, or a combination of intravenous AmB with intrathecal AmB, flucytosine or fluconazole. All indwelling central nervous system devices were externalized or removed. Four adults died of the disease. Three of them had malignancy and had received <48 h of antifungal therapy. For adult patients with malignancy, early diagnosis and alternative treatment modalities with newer antifungal agents may be needed.

Tigecycline and colistin susceptibility of Chryseobacterium meningosepticum isolated from blood in Taiwan

Sir, Chryseobacterium meningosepticum is a non-glucoseermenting, Gram-negative, aerobic bacillus widely distributed in oil, plants and water. It is not normally present as part of the human icroflora [1]. Clinical disease associated with C. meningosepticum nfection primarily occurs in premature newborns and infants. previous study described meningitis in 84% of clinical cases, ith a 57% mortality rate [1]. Adult C. meningosepticum infection s rare and primarily occurs in severely immunocompromised atients [1]. Chryseobacterium meningosepticum can cause a variety f infections in adults and many cases have been reported in aiwan [2–4]. Several studies have described broad resistance to any Gram-negative antimicrobials, including extended-spectrum ephalosporins, aztreonam, carbapenems and aminoglycosides 5–7]. However, C. meningosepticum displayed variable suscepibility to Gram-positive antimicrobials, including rifampicin, lindamycin, erythromycin, trimethoprim/sulfamethoxazole, uinolones and vancomycin [5–7]. Chryseobacterium meningosepicum infections were generally associated with a poor outcome in everal studies, with a cumulative mortality of 33% among posteonates [1]. A recent Taiwanese study revealed a high mortality ate (42.9%) in patients with hospital-acquired C. meningosepticum nfection [4]. Tigecycline exhibits in vitro activity against many Gram-positive nd Gram-negative microorganisms, including multiresistant

Risk factors for imipenem-nonsusceptible Acinetobacter nosocomialis bloodstream infection

BACKGROUND The emergence of imipenem-nonsusceptible (INS) Acinetobacter baumannii complex has had a great impact on healthcare systems worldwide. Understanding the risk factors related to INS infection is useful for infection control. The risk factors for INS A. baumannii have been well documented; however, the risk factors related to INS Acinetobacter nosocomialis infection lack documentation. The purpose of this study was to identify the risk factors associated with INS A. nosocomialis bacteremia. METHODS This retrospective 9-year study included 329 adults with A. nosocomialis bacteremia in a tertiary medical center in Taiwan. Acinetobacter nosocomialis was identified using a multiplex polymerase chain reaction method and sequence analysis of a 16S-23S intergenic spacer. RESULTS Among 329 patients with A. nosocomialis bacteremia, 67 had INS isolates (20.4%). Patients with INS isolates tended to have a more severe form of the diseases [with ICU admission and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score], specific underlying diseases (associated with chronic lung diseases and end-stage renal diseases, but less commonly alcoholism and chemotherapy), multiple invasive procedures, pneumonia as a primary focus of infection, and prior antimicrobial use (sulbactam, antipseudomonal penicillins, aminoglycosides, and carbapenems). Multivariable analysis showed that ICU admission, chronic lung diseases, arterial line catheterization, total parenteral nutrition, and prior use of carbapenems were independent risk factors; prior use of carbapenems was found to be the most influential (odds ratio 6.36, 95% confidence interval 2.00-20.21; p = 0.002). CONCLUSION To our knowledge, this is the first study describing the risk factors associated with INS A. nosocomialis bacteremia. Regulated antibiotic control policy, especially for carbapenem, and infection control measures targeting patients hospitalized in ICU, with chronic lung diseases and multiple invasive procedures, may be helpful in reducing INS A. nosocomialis infection.