Yi-Tsung Lin

Bacteremic community-acquired pneumonia due to Klebsiella pneumoniae: Clinical and microbiological characteristics in Taiwan, 2001-2008

BackgroundKlebsiella pneumoniae is the major cause of community-acquired pyogenic infections in Taiwan. This retrospective study evaluated the clinical and microbiological characteristics of bacteremic community-acquired pneumonia due to K. pneumoniae in Taiwanese adults.MethodsThe clinical characteristics of bacteremic community-acquired pneumonia (CAP) in adults due to K. pneumoniae were compared to those of adults with bacteremic CAP due to Streptococcus pneumoniae at a tertiary medical center in Taiwan from 2001-2008. Risk factors for mortality of bacteremic CAP due to K. pneumoniae were analyzed. All clinical isolates of K. pneumoniae were examined for capsular serotypes, hypermucoviscosity phenotype, aerobactin and rmpA gene.ResultsK. pneumoniae was the dominant cause of bacteremic CAP and was associated with a more fulminant course and a worse prognosis than bacteremic CAP due to Streptococcus pneumoniae. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality. Serotype K1 and K2 comprised around half of all isolates. There were no significant differences in the clinical characteristics of patients with bacteremic CAP due to K1/K2 and non-K1/K2 isolates. Hypermucoviscosity phenotype as well as the aerobactin and rmpA genes were highly prevalent in the K. pneumoniae isolates.ConclusionsK. pneumoniae continued to be the dominant cause of bacteremic CAP in Taiwanese adults during 2001-2008. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality from K. pneumoniae bacteremic CAP. Serotypes K1/K2 comprised around half of all isolates, but did not predispose patients to a poor clinical outcome. Physicians should be aware of the poor prognosis of any patient with bacteremic K. pneumoniae CAP and monitor these patients more closely.

Impact of Appropriate Antimicrobial Therapy on Mortality Associated With Acinetobacter baumannii Bacteremia: Relation to Severity of Infection

BACKGROUND The efficacy of antimicrobial therapy for Acinetobacter baumannii bacteremia has been difficult to establish because of confounding by underlying diseases, severity of infection, and differences in the pathogenicity of Acinetobacter species. This retrospective study was conducted to evaluate the effect of appropriate antimicrobial therapy on 14-day mortality after adjustment for multiple risk factors. METHODS The population consisted of 252 patients with monomicrobial A. baumannii bacteremia admitted to a large teaching hospital in Taiwan. The isolates were identified to species level using reference molecular methods. Predictors of 14-day mortality were determined by logistic regression analysis. The influence of severity of infection, determined by Acute Physiology and Chronic Health Evaluation (APACHE) II score, on the impact of appropriate use of antimicrobials on 14-day mortality was assessed by including an interaction term. RESULTS The overall 14-day mortality rate was 29.8% (75 of 252 patients). The unadjusted mortality rate for appropriate antimicrobial therapy was 13.2% (12 of 91 patients). Appropriate therapy was independently associated with reduced mortality (odds ratio [OR], 0.22; 95% confidence interval [CI], .01-.50; P < .001), and the effect was influenced by APACHE II score (OR for interaction term, 0.90; 95% CI, .82-.98; P= .02). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with high APACHE II scores (OR for patients with scores >25 and ≤ 35, 0.16 [95% CI, .07-.37]; OR for those with scores >35, 0.06; 95% CI, .01-.25). CONCLUSIONS Appropriate antimicrobial therapy significantly reduced 14-day mortality for A. baumannii bacteremia in severely ill patients.

Klebsiella pneumoniae in gastrointestinal tract and pyogenic liver abscess.

To determine the role of gastrointestinal carriage in Klebsiella pneumoniae liver abscess, we studied 43 patients. Bacterial isolates from liver and fecal samples from 10 patients with this condition and 7 healthy carriers showed identical serotypes and genotypes with the same virulence. This finding indicated that gastrointestinal carriage is a predisposing factor for liver abscess.

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.

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).

Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy chinese and overseas chinese adults in Asian countries

BackgroundCapsular serotypes K1 and K2 of Klebsiella pneumoniae are thought to the major virulence determinants responsible for liver abscess. The intestine is one of the major reservoirs of K. pneumoniae, and epidemiological studies have suggested that the majority of K. pneumoniae infections are preceded by colonization of the gastrointestinal tract. The possibility of fecal-oral transmission in liver abscess has been raised on the basis of molecular typing of isolates. Data on the serotype distribution of K. pneumoniae in stool samples from healthy individuals has not been previously reported. This study investigated the seroepidemiology of K. pneumoniae isolates from the intestinal tract of healthy Chinese in Asian countries. Stool specimens from healthy adult Chinese residents of Taiwan, Japan, Hong Kong, China, Thailand, Malaysia, Singapore, and Vietnam were collected from August 2004 to August 2010 for analysis.ResultsSerotypes K1/K2 accounted for 9.8% of all K. pneumoniae isolates from stools in all countries. There was no significant difference in the prevalence of K1/K2 isolates among the countries excluding Thailand and Vietnam. The antimicrobial susceptibility pattern was nearly the same in K. pneumoniae isolates. The result of pulsed-field gel electrophoresis revealed no major clonal cluster of serotype K1 isolates.ConclusionsThe result showed that Chinese ethnicity itself might be a major factor predisposing to intestinal colonization by serotype K1/K2 K. pneumoniae isolates. The prevalent serotype K1/K2 isolates may partially correspond to the prevalence of K. pneumoniae liver abscess in Asian countries.

Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan

ABSTRACT Colistin is one of the antibiotics of last resort for the treatment of carbapenem-resistant Klebsiella pneumoniae infection. This study showed that capsular type K64 (50%) and ST11 (53.9%) are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan. The interruption of transcripts (38.5%) and amino acid mutation (15.4%) in mgrB are the major mechanisms contributing to colistin resistance. In addition, novel single amino acid changes in MgrB (Stop48Tyr) and PhoQ (Leu26Pro) were observed to contribute to colistin resistance.

Klebsiella pneumoniae liver abscess in diabetic patients: association of glycemic control with the clinical characteristics

BackgroundKlebsiella pneumoniae liver abscess (KPLA) has been reported with increasing frequency in East Asian countries in the past 3 decades, especially in Taiwan and Korea. Diabetes is a well-known risk factor for KPLA and highly associated with septic metastatic complications from KPLA. We investigated the association of glycemic control in diabetic patients with the clinical characteristics of KPLA in Taiwan.MethodsAdult diabetic patients with KPLA were identified retrospectively in a medical center from January 2007 to January 2012. Clinical characteristics were compared among patients with different levels of current hemoglobin A1c (HbA1c). Risk factors for metastatic infection from KPLA were analyzed.ResultsPatients with uncontrolled glycemia (HbA1c ≥ 7%) were significantly younger than those with controlled glycemia (HbA1c < 7%). Patients with uncontrolled glycemia had the trend to have a higher rate of gas-forming liver abscess, cryptogenic liver abscess, and metastatic infection than those with controlled glycemia. Cryptogenic liver abscess and metastatic infection were more common in the poor glycemic control group (HbA1c value >; 10%) after adjustment with age. HbA1c level and abscess < 5 cm were independent risk factors for metastatic complications from KPLA.ConclusionsGlycemic control in diabetic patients played an essential role in the clinical characteristics of KPLA, especially in metastatic complications from KPLA.

Pyogenic Liver Abscess as the Initial Manifestation of Underlying Hepatocellular Carcinoma

BACKGROUND Pyogenic liver abscess and hepatocellular carcinoma are common in Taiwan. We investigated the frequency of, risk factors for, and prognosis of pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma over a 12-year period in Taiwan. METHODS We extracted 32,454 patients with pyogenic liver abscess from a nationwide health registry in Taiwan during the period 1997-2008. The frequency of and risk factors for pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma were determined. The prognosis of these patients was compared with patients with hepatocellular carcinoma but without liver abscess. RESULTS A total of 698 (2.15%) patients presented with liver abscess as the initial manifestation of underlying hepatocellular carcinoma during the 12-year period. Liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, and age ≥65 years were independent risk factors for liver abscess as the initial manifestation of underlying hepatocellular carcinoma. Furthermore, these patients had a lower 2-year survival rate than patients with hepatocellular carcinoma but without liver abscess (30% vs 37%; P=.004). CONCLUSIONS The prognosis of patients who presented with pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma was poor. Physicians should not ignore the possibility of underlying hepatocellular carcinoma in patients with risk factors for the disease in regions with a high prevalence of both pyogenic liver abscess and hepatocellular carcinoma.

The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice

ABSTRACT The resistance-nodulation-division (RND)-type efflux pump is one of the causes of the multidrug resistance of Stenotrophomonas maltophilia. The roles of the RND-type efflux pump in physiological functions and virulence, in addition to antibiotic extrusion, have attracted much attention. In this study, the contributions of the constitutively expressed SmeYZ efflux pump to drug resistance, virulence-related characteristics, and virulence were evaluated. S. maltophilia KJ is a clinical isolate of multidrug resistance. The smeYZ isogenic deletion mutant, KJΔYZ, was constructed by a gene replacement strategy. The antimicrobial susceptibility, virulence-related physiological characteristics, susceptibility to human serum and neutrophils, and in vivo virulence between KJ and KJΔYZ were comparatively assessed. The SmeYZ efflux pump contributed resistance to aminoglycosides and trimethoprim-sulfamethoxazole. Inactivation of smeYZ resulted in attenuation of oxidative stress susceptibility, swimming, flagella formation, biofilm formation, and secreted protease activity. Furthermore, loss of SmeYZ increased susceptibility to human serum and neutrophils and decreased in vivo virulence in a murine model. These findings suggest the possibility of attenuation of the resistance and virulence of S. maltophilia with inhibitors of the SmeYZ efflux pump.