Wang-Huei Sheng

Influence of Genospecies of Acinetobacter baumannii Complex on Clinical Outcomes of Patients with Acinetobacter Bacteremia

BACKGROUND acinetobacter baumannii complex infections are increasing in prevalence and are associated with a high mortality. Biochemical classification tests cannot differentiate A. baumannii (genospecies 2) from other genospecies. Genospecies typing offers a potential tool to determine whether there are major differences in pathogenicity among the genospecies. METHODS adult patients with A. baumannii complex bacteremia in intensive care units were prospectively observed from January 2007 through July 2009. A. baumannii complex was identified by biochemical methods and the Phoenix bacterial identification system. Genospecies were identified by 16S-23S ribosomal RNA intergenic-spacer sequencing. RESULTS among the 135 patients with A. baumannii complex bacteremia, 87 (64.4%) had isolates that belonged to genospecies 2, 36 (26.7%) had isolates that belonged to genospecies 13TU, and 12 (8.9%) had isolates that belonged to genospecies 3. Patients with A. baumannii (genospecies 2) bacteremia were more likely to have pneumonia than were patients with bacteremia due to genospecies 13TU (63.2 % vs 27.8%; P =.001), whereas patients with bacteremia due to genospecies 13TU were more likely to have primary bacteremia (69.4% vs 20.7%; P <.001). Genospecies 2 was less susceptible to antibiotics than were other genospecies. It was associated with a higher rate of mortality than was genospecies 13TU (58.6% vs 16.7%; P < .001). On multivariate analysis, genospecies 2 was an independent predictor of mortality (odds ratio, 5.46; 95% confidence interval, 2.00-14.91; P = .001). CONCLUSIONS genospecies 2 of the A. baumannii complex was associated with greater resistance to antibiotics and higher mortality among bacteremic patients, compared with other genospecies, especially genospecies 13TU. These findings emphasize the need to focus on genospecies to better understand the pathogenesis and epidemiology of infections caused by the A. baumannii complex.

Distribution of Extended-Spectrum β-Lactamases, AmpC β-Lactamases, and Carbapenemases among Enterobacteriaceae Isolates Causing Intra-Abdominal Infections in the Asia-Pacific Region: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART)

ABSTRACT The increasing trend of β-lactam resistance among Enterobacteriaceae is a worldwide threat. Enterobacteriaceae isolates causing intra-abdominal infections (IAI) from the Study for Monitoring Antimicrobial Resistance Trends (SMART) collected in 2008 and 2009 from the Asia-Pacific region were investigated. Detection of extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases was performed by multiplex PCR. A total of 699 Enterobacteriaceae isolates with positive genotypic results, included Escherichia coli (n = 443), Klebsiella pneumoniae (n = 187), Enterobacter cloacae (n = 45), Klebsiella oxytoca (n = 9), Citrobacter freundii (n = 5), Proteus mirabilis (n = 3), Enterobacter aerogenes (n = 2), Morganella morganii (n = 2), and one each of Enterobacter asburiae, Proteus vulgaris, and Providencia rettgeri were analyzed. Nearly 20% of these β-lactamase-producing Enterobacteriaceae isolates were from community-associated IAI. CTX-M (588 isolates, including 428 [72.8%] with CTX-M-15) was the most common ESBL, followed by SHV (n = 59) and TEM (n = 4). CMY (n = 110, including 102 [92.7%] with CMY-2) was the most common AmpC β-lactamase, followed by DHA (n = 46) and ACT/MIR (n = 40). NDM (n = 65, including 62 [95.4%] with NDM-1) was the most common carbapenemase, followed by IMP (n = 7) and OXA (n = 7). Isolates from hospital-associated IAI had more complicated β-lactamase combinations than isolates from the community. Carbapenemases were all exclusively detected in Enterobacteriaceae isolates from India, except that IMP β-lactamases were also detected in Philippines and Australia. CTX-M β-lactamases were the predominant ESBLs produced by Enterobacteriaceae causing IAI in the Asia-Pacific region. Emergence of CTX-M-15-, CMY-2-, and NDM-1-producing Enterobacteriaceae isolates is of major concern and highlights the need for further surveillance in this area.

Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter pylori infection: a randomised comparative trial with crossover design

Background The efficacy of a levofloxacin-based regimen as the first-line treatment and a clarithromycin-based regimen as the second-line treatment for Helicobacter pylori infection remains unknown. The aim of this study was to assess the eradication rates of these two regimens using different administration sequences. Methods Eligible patients were randomised to receive LAL: levofloxacin (750 mg once a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days, or CAL: clarithromycin (500 mg twice a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days. Patients with positive [13C]urea breath test after treatment were retreated with the rescue regimen in a crossover manner for 10 days. Result When used as first-line treatment (n=432), the eradication rates of LAL (n=217) and CAL (n=215) were 74.2 and 83.7% (p=0.015) in the intent-to-treat (ITT) analysis, and 80.1 and 87.4% (p=0.046) in the per-protocol (PP) analysis, respectively. When used as second-line treatment, the eradication rates of LAL (n=26) and CAL (n=40) were 76.9 and 60% (p=0.154) in the ITT analysis, and 80 and 61.5% (p=0.120) in the PP analysis, respectively. The overall eradication rates of CAL followed by LAL were better than the reverse sequence in both the ITT analysis (93% vs 85.3%, p=0.01) and the PP analysis (97.6% vs 92.5%, p=0.019). The eradication rate was significantly lower in the presence of levofloxacin resistance in the LAL group (50% vs 84.4%, p=0.018) and clarithromycin resistance in the CAL group (44.4% vs 90.7%, p=0.002). Conclusion CAL achieved a higher eradication rate than LAL as the first-line treatment, but not as the second-line treatment. The strategy of using CAL as the initial treatment and LAL as the rescue regimen achieved higher eradication rates than the reverse sequence. Clinical trial number NCT00816140.

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.

Impact of Chronic Hepatitis B Virus (HBV) Infection on Outcomes of Patients Infected with HIV in an Area Where HBV Infection Is Hyperendemic

Between June 1994 and February 2003, a total of 111 human immunodeficiency virus (HIV)-infected patients with chronic hepatitis B virus (HBV) coinfection and 387 HIV-infected patients without HBV or hepatitis C virus coinfection were prospectively observed to assess the impact of HBV infection on outcomes of HIV-infected patients. After a median duration of observation of 25 months, coinfected patients were more likely to develop hepatitis (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [CI], 1.69-3.82) and hepatic decompensation (adjusted odds ratio [AOR], 9.94; 95% CI, 1.89-52.35). Although similar proportions of the 2 patient groups had an increase in the CD4 count by > or =100x10(6) cells/L (AOR, 0.78; 95% CI, 0.45-1.36) and development of new opportunistic illnesses (AOR, 0.94; 95% CI, 0.53-1.66), HBV-infected patients had an increased risk for virologic failure (AOR, 1.76; 95% CI, 1.03-2.99) and death (AHR, 1.71; 95% CI, 1.19-2.47) after highly active antiretroviral therapy was initiated.

Mycobacterium abscessus Complex Infections in Humans

New treatments, rapid and inexpensive identification methods, and measures to contain nosocomial transmission and outbreaks are urgently needed.

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.

Evaluation of antiseptic-impregnated central venous catheters for prevention of catheter-related infection in intensive care unit patients.

Central venous catheterization represents a significant medical advancement, particularly in the treatment of critical ill. However, there is a high risk of central venous catheters-related infection. A novel antiseptic central venous catheter, made of polyurethane and impregnated with chlorhexidine and silver sulfadiazine, was developed to reduce the risk of catheters-related infection. In this study, we did a randomized clinical study to determine the efficacy by using antiseptic catheters for the prevention of central venous catheters-related infection in the intensive care units. A total of 204 patients with 235 central venous catheters were studied at the surgical intensive care units at National Taiwan University Hospital between November 1998 and June 1999. Participants received either a standard triple-lumen polyurethane catheter or an antiseptic catheter (Arrow International, Reading, Pennsylvania, USA). Both were indistinguishable from each other. Compared to standard polyurethane catheters, antiseptic catheters were less likely to be colonized by microorganisms when they were cultured at the removal (8.0 versus 20.0 colonized catheters per 100 catheters; relative risk 0.34 [95% CI, 0.15 to 0.74]; p<0.01). There was no significant differences between both groups in catheter-related infections (0.9 versus 4.9 infections per 100 catheters; relative risk 0.17 [95% CI, 0.03 to 1.15]; p = 0.07). Gram-positive cocci and fungi were more likely to colonize in the standard polyurethane catheters (p = 0.06 and 0.04, compared to antiseptic catheters respectively). Two of our cases in the control group died directly due to catheter-related candidemia. No adverse reactions such as hypersensitivity or leukopenia were found in the antiseptic catheter group. Our study showed that central venous catheters with antiseptic coating were safe and had less risk of colonization of bacteria and fungi than standard catheters in the critically ill patients.

Effectiveness and Limitations of Hand Hygiene Promotion on Decreasing Healthcare–Associated Infections

Background Limited data describe the sustained impact of hand hygiene programs (HHPs) implemented in teaching hospitals, where the burden of healthcare-associated infections (HAIs) is high. We use a quasi-experimental, before and after, study design with prospective hospital-wide surveillance of HAIs to assess the cost effectiveness of HHPs. Methods and Findings A 4-year hospital-wide HHP, with particular emphasis on using an alcohol-based hand rub, was implemented in April 2004 at a 2,200-bed teaching hospital in Taiwan. Compliance was measured by direct observation and the use of hand rub products. Poisson regression analyses were employed to evaluate the densities and trends of HAIs during the preintervention (January 1999 to March 2004) and intervention (April 2004 to December 2007) periods. The economic impact was estimated based on a case-control study in Taiwan. We observed 8,420 opportunities for hand hygiene during the study period. Compliance improved from 43.3% in April 2004 to 95.6% in 2007 (p<.001), and was closely correlated with increased consumption of the alcohol-based hand rub (r = 0.9399). The disease severity score (Charlson comorbidity index) increased (p = .002) during the intervention period. Nevertheless, we observed an 8.9% decrease in HAIs and a decline in the occurrence of bloodstream, methicillin-resistant Staphylococcus aureus, extensively drug-resistant Acinetobacter baumannii, and intensive care unit infections. The intervention had no discernable impact on HAI rates in the hematology/oncology wards. The net benefit of the HHP was US

Safety and efficacy of intravenous colistin (colistin methanesulphonate) for severe multidrug-resistant Gram-negative bacterial infections

5,289,364, and the benefit-cost ratio was 23.7 with a 3% discount rate. Conclusions Implementation of a HHP reduces preventable HAIs and is cost effective.