Jiun-Ling Wang

Comparison of Both Clinical Features and Mortality Risk Associated with Bacteremia due to Community-Acquired Methicillin-Resistant Staphylococcus aureus and Methicillin-Susceptible S. aureus

BACKGROUND The majority of research about community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has focused on skin and soft-tissue infections. No literature has been published on the clinical features and outcomes of adult patients with CA-MRSA bacteremia in comparison with patients with community-acquired methicillin-susceptible S. aureus (CA-MSSA) bacteremia. METHODS From 1 January 2001 through 31 December 2006, the demographic data and outcome of 215 consecutive adult patients admitted to a tertiary care center in Taiwan with S. aureus bacteremia (age, >16 years) who fulfilled the criteria for community-acquired S. aureus bacteremia were collected for analysis. RESULTS The mean age (+/-SD) was 56.8+/-20.5 years. There were 30 patients (14%) with CA-MRSA bacteremia and 185 (86%) patients with CA-MSSA bacteremia. Cutaneous abscess (odds ratio, 5.46; 95% confidence interval, 1.66-17.94) and necrotizing pneumonia (odds ratio, 24.81; 95% confidence interval, 2.63-234.03) were the independent predictors of CA-MRSA bacteremia; endovascular infection was the only independent predictor of CA-MSSA bacteremia. After Cox regression analysis, the independent significant risk factors for 30-day mortality included increased age, shock, and thrombocytopenia (<100,000 cells/microL). After adjustment, the day 30 mortality of patients with CA-MRSA bacteremia was not significantly higher than that of patients with CA-MSSA bacteremia (adjusted hazard ratio, 1.01; 95% confidence interval, 0.30-3.39; P = .986). Most (92%) of 25 available CA-MRSA isolates were multilocus sequence typing 59. CONCLUSIONS The number of adult patients with CA-MRSA bacteremia increased with time, and the disease was associated with more necrotizing pneumonia and cutaneous abscess but less endovascular infection than was CA-MSSA bacteremia. Patients with CA-MRSA bacteremia did not have higher mortality than did patients with CA-MSSA, even though most of the patients with CA-MRSA bacteremia did not receive empirical glycopeptide therapy.

Systematic Review and Meta-Analysis of the Tolerability and Hepatotoxicity of Antifungals in Empirical and Definitive Therapy for Invasive Fungal Infection

ABSTRACT To evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity.

Changing Bacteriology of Adult Community-Acquired Lung Abscess in Taiwan: Klebsiella pneumoniae versus Anaerobes

BACKGROUND Most literature regarding lung abscess focuses on anaerobic bacterial lung abscess, and aerobic gram-negative bacillary infection is less frequently discussed. This study was conducted to investigate the bacteriology of community-acquired lung abscess and to improve the empirical therapeutic strategy for adults with community-acquired lung abscess. METHODS We reviewed and analyzed data on 90 consecutive adult cases of bacteriologically confirmed community-acquired lung abscess treated during 1995-2003 at a tertiary university hospital in Taiwan. RESULTS We found that a high proportion (21%) of cases of lung abscess were due to Klebsiella pneumoniae infection, which differs from the findings of previous studies. Lung abscess due to K. pneumoniae was associated with underlying diabetes mellitus (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.0-18.4; P = .039) and negatively correlated with a time from onset of symptoms to diagnosis of >30 days (OR, 0.2; 95% CI, 0.1-0.7; P = .008). A higher percentage of patients with K. pneumoniae lung abscess had concomitant bacteremia (OR, 9.4; 95% CI, 1.1-81.9; P = .032), delayed defervesence (OR, 9.2; 95% CI, 1.8-47.8; P = .004), and multiple cavities noted on radiographs (OR, 11.0; 95% CI, 1.3-94.9; P = .015), compared with patients with anaerobic bacterial lung abscess. The rate of nonsusceptibility to clindamycin and penicillin among anaerobes and Streptococcus milleri group isolates increased. CONCLUSION K. pneumoniae has become a more common cause of lung abscess than before, and a high proportion of anaerobes and S. milleri strains have become resistant to penicillin and clindamycin. A beta-lactam/beta-lactamase inhibitor or second- or third-generation cephalosporin with clindamycin or metronidazole is suggested as empirical antibiotic therapy for community-acquired lung abscess.

Longitudinal analysis of chlorhexidine susceptibilities of nosocomial methicillin-resistant Staphylococcus aureus isolates at a teaching hospital in Taiwan

BACKGROUND Chlorhexidine has been widely used for hand hygiene to prevent transmission of nosocomial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). However, data on longitudinal surveillance of the susceptibility of MRSA isolates to chlorhexidine are limited. METHODS A total of 240 nosocomial MRSA isolates obtained in 1990, 1995, 2000 and 2005 at National Taiwan University Hospital (NTUH), a hospital where chlorhexidine gluconate was used for hand hygiene for more than 20 years, were included in the study. Chlorhexidine susceptibility, molecular typing using multilocus sequence typing and distribution of the qacA/B gene of these MRSA isolates were studied. RESULTS The proportion of tested MRSA with a high MIC of chlorhexidine (>or=4 mg/L) was 1.7% in 1990, 50% in 1995, 40% in 2000 and 46.7% in 2005. Among these 83 isolates with high chlorhexidine MICs, 55.4% carried the qacA/B gene. MRSA isolates carrying the qacA/B gene were first detected in 1995 and belonged to a single clone at that time. However, the qacA/B gene was detected in MRSA isolates belonging to seven different clones in 2005. CONCLUSIONS The proportion of tested MRSA isolates with high chlorhexidine MICs at NTUH increased from 1990 to 1995 and remained steady thereafter. The presence of the qacA/B gene may contribute to the spread of specific MRSA clones.

Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in Taiwan: Mortality analyses and the impact of vancomycin, MIC = 2 mg/L, by the broth microdilution method

BackgroundPrevious studies regarding the prognosis of patients infected with MRSA isolates characterized by a high minimum inhibitory concentration (MIC) for vancomycin have generally used a commercial Etest. Little research has been conducted on determining the vancomycin susceptibility of MRSA using a reference microdilution. Additionally, there is discordance between the MIC result from an Etest and the value determined using the reference microdilution method.MethodsUsing a reference microdilution method, we determined the MIC of vancomycin for isolates from 123 consecutive patients with nosocomial MRSA bacteremia. The clinical features and outcome for these patients were recorded and the MRSA isolates were genotyped.ResultsAmong the 123 non-duplicated isolates, 21.1% had a MIC = 2 mg/L, 76.4% had a MIC = 1 mg/L and 2.4% had MIC = 0.5 mg/L. Patients with MRSA bacteremia in the ICU or those who had been hospitalized for a long time were more likely to be infected with strains of high vancomycin MIC MRSA (MIC = 2 mg/L; p < 0.05). Cox regression analysis demonstrated that the high MIC group had a significantly higher 30-day mortality than the low MIC group (HR: 2.39; 95% CI: 1.20-4.79; p = 0.014). Multivariate analyses indicated that the presence of high MIC isolates, pneumonia, post-cardiothoracic surgery and a high Charlson comorbidity index were all independent predictors of a 30-day mortality. Genotyping of these high vancomycin MIC isolates demonstrated that SCCmec III, spa type037, was the predominant strain (> 80%). The rates of resistance to trimethoprim/sulfamethoxazole, gentamicin, levofloxacin, rifampin and tetracycline were also higher in the high MIC group than in the isolates belonging to low MIC group (p < 0.05).ConclusionsIn a high vancomycin MIC group in Taiwan, SCCmec III, spa type t037, was the predominant strain of MRSA identified. Patients with MRSA bacteremia in the ICU or who had prolonged hospitalization were more likely to be infected with S. aureus strains with high vancomycin MICs. The mortality rate was higher among patients infected with these strains compared to patients infected with low MIC strains.

Bacteremia Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli Sequence Type ST131 and Non-ST131 Clones: Comparison of Demographic Data, Clinical Features, and Mortality

ABSTRACT Escherichia coli producing the highly virulent, multidrug-resistant, CTX-M-15 extended-spectrum β-lactamase (ESBL), sequence type 131 (ST131), has emerged on three continents since the late 2000s. We described the molecular epidemiology, clinical features, and outcome of ESBL-producing E. coli bacteremia in Taiwan from 2005 to 2010. This study aims to determine whether the risk factors, clinical features, and outcomes of the ST131 isolate differ from those of non-ST131 isolates. From 2005 to 2010, we collected 122 nonduplicated, consecutive, ESBL-producing E. coli isolates from bloodstream infections in a 1,200-bed hospital in Taiwan. Isolates were characterized using multilocus sequence typing. Demographic data, clinical features, and outcomes were collected from medical chart records. Thirty-six (29.5%) patients with bacteremia with ESBL-producing E. coli ST131 were identified. Patients with clone ST131 were more likely to have secondary bacteremia and noncatheterized urinary tract infections (P < 0.05). Secondary bacteremia (odds ratio [OR], 5.05; 95% confidence interval [CI], 1.08 to 23.56) and urinary catheter nonuse (OR, 3.77; 95% CI, 1.17 to 12.18) were independent risk factors for the ST131 clone after adjustment. Mortality rates at day 28 were similar in ST131 and non-ST131 populations. Independent risk factors predicting mortality at day 28 included malignancy, shock, and hospital-acquired bacteremia. In ESBL-producing E. coli bloodstream infections, the ST131 clone was not associated with health-care-associated risk factors, such as urinary catheter use or antibiotic exposure. Although highly virulent and multidrug resistant, the ST131 clone was not associated with higher mortality than non-ST131 clones.

Sphingomonas paucimobilis Bacteremia in Humans: 16 Case Reports and a Literature Review

BACKGROUND/PURPOSE Sphingomonas paucimobilis is a glucose-nonfermenting Gram-negative bacillus that is widely distributed in both natural environment and hospitals. Various infections in humans have been reported, but most have been limited to sporadic case reports. The aim of this study was to describe the clinical characteristics and manifestations of S. paucimobilis bacteremia. We also reviewed the literature on S. paucimobilis bacteremia. METHODS Cases of S. paucimobilis bacteremia were identified retrospectively at a university-affiliated hospital in Taiwan. In addition, relevant case reports were identified through PubMed and reviewed. RESULTS From April 2004 to April 2008, 42 cases of S. paucimobilis bacteremia were identified in this study. Among them, 16 cases were identified from E-Da hospital, Kaohsiung, Taiwan and 26 cases from the literature review. The median age of patients was 48.5 years and 57.1% were male. The most common comorbidities included malignancy (57.1%), immunosuppressant use (40.5%), and diabetic mellitus (11.9%). Hospital-acquired bacteremia accounted for 69.0% of infections. Primary bacteremia and catheter-related bloodstream infection were found in 35.7% and 33.3% respectively. The most effective antibiotics were fluoroquinolones, carbapenems, and beta-lactam/beta-lactamase inhibitor combinations. All 42 patients survived the S. paucimobilis bacteremic episodes, but three patients experienced septic shock. CONCLUSION S. paucimobilis can cause infections in healthy as well as immunocompromised individuals. Although it is an organism of low clinical virulence, infection caused by S. paucimobilis can lead to septic shock. Further clinical research is required to characterize this infection.

Clinical Manifestations, Laboratory Findings, and Treatment Outcomes of SARS Patients

Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.

Association between Contaminated Faucets and Colonization or Infection by Nonfermenting Gram-Negative Bacteria in Intensive Care Units in Taiwan

ABSTRACT This study was designed to determine the strength of the association between the isolation of nonfermentative gram-negative bacilli (NFGNB) from tap water faucet aerators and the prevalence of colonization or infection of patients in intensive care units (ICUs). Surveillance cultures were obtained during a 4-month period from 162 faucet aerators located in seven different ICUs. The prevalence of colonization or infection of ICU patients with NFGNB was determined by prospective surveillance during the same period. Fifty four (33%) of the faucet aerators contained NFGNB. Among the 66 NFGNB isolated from faucet aerators, the most frequently encountered ones were Sphingomonas paucimobili (26 isolates), Pseudomonas aeruginosa (14 isolates), Chryseobacterium meningosepticum (13 isolates), Achromobacter xylosoxidans (6 isolates), Burkholderia cepacia (4 isolates), and Stenotrophomonas maltophilia (3 isolates). Acinetobacter baumannii was not recovered. The most common NFGNB isolated from ICU patients were P. aeruginosa and A. baumannii. There was a significant correlation between the overall prevalence of NFGNB in faucet aerators and their prevalence in exposed ICU patients (Spearman r = 0.821, P = 0.02). There was also a significant correlation between the prevalence of C. meningosepticum in faucet aerators and its prevalence among ICU patients (Spearman r = 0.847, P = 0.016). The electrokaryotypes of four clinical isolates of C. meningosepticum were similar to those of faucet isolates. Measures directed at making the water supply safe may prevent infection by C. meningosepticum and other waterborne pathogens.

Clinical Features and Outcome of Tuberculosis in Solid Organ Transplant Recipients

Background:Taiwan is an area with moderate to high incidence of Mycobacterium tuberculosis infection. The risk of M tuberculosis infection in transplantation recipients is considered to be significant. Our aim in this study was to investigate the clinical spectrums of M tuberculosis–infected transplantation recipients in a southeast Asian country, Taiwan. Methods:We retrospectively analyzed the demographic data, clinical features, treatment, and outcome of M tuberculosis infection in kidney, heart, and liver transplant recipients from May 1996 to April 2005 at the National Taiwan University Hospital. Results:Fifteen patients who had received solid organ transplantation developed tuberculosis (kidney = 6, heart = 7, liver = 2). The median duration from transplantation to diagnosis of tuberculosis was 31 months. The cumulative incidence of post-transplantation tuberculosis was 2.0% (15/760), ie, ∼3 times that of the general population. Ten patients (66.7%) had pulmonary tuberculosis, 1 (6.7%) had extrapulmonary tuberculosis, and 4 (26.7%) had disseminated tuberculosis. Nine patients completed the anti-tuberculosis treatment; the median treatment duration was 12 months (pulmonary: 9 months; extrapulmonary: 13.5 months). No treatment failure was noted in patients receiving the complete treatment course. The graft failure and mortality rates of post-transplantation tuberculosis were 13.3% each (2/15). The tuberculosis-associated mortality rate was 6.7% (1/15). Conclusions:Cumulative incidence of tuberculosis was slightly higher in transplant recipients than in the general population in Taiwan. Conventional 4-combined anti-tuberculosis regimen for 12 months can treat the potentially fatal infection successfully in post-transplantation tuberculosis patients without recurrence.