Risk factors and outcome for colistin-resistant Acinetobacter nosocomialis bacteraemia in patients without previous colistin exposure.

The clinical characteristics of patients with colistin-resistant Acinetobacter baumannii bacteraemia have been documented, but those of patients with bacteraemia caused by other Acinetobacter species remain unknown. Previous exposure to colistin has been shown to be associated with the emergence of colistin resistance, but may be not the only predisposing factor. In the current study, we highlight the risk and outcome of patients without previous exposure to colistin who acquired colistin-resistant Acinetobacter nosocomialis (ColRAN) bacteraemia. This 11-year single-centre retrospective study analysed 58 patients with ColRAN bacteraemia and 213 patients with colistin-susceptible A. nosocomialis (ColSAN) bacteraemia. Antimicrobial susceptibilities were determined with an agar dilution method. The clonal relationship of ColRAN isolates was determined with pulsed-field gel electrophoresis. A conjugation mating-out assay was conducted to delineate the potential transfer of colistin resistance genes. Multivariable analysis was performed to evaluate the risk factors for ColRAN bacteraemia. Chronic obstructive pulmonary disease (COPD) was independently associated with ColRAN bacteraemia (OR 3.04; 95% CI 1.45-6.37; p 0.003). Patients with ColRAN bacteraemia had higher APACHE II scores, but the two groups showed no significant differences in 14-day mortality (10.3% vs. 10.3%) or 28-day mortality (15.5% vs. 15.0%). ColRAN isolates had greater resistance than ColSAN isolates to all antimicrobial agents except for ciprofloxacin (0% vs. 6.6%). There were 16 different ColRAN pulsotypes, and two major clones were found. Colistin resistance did not transfer to colistin-susceptible A. baumannii or A. nosocomialis. These results show that COPD is an independent risk factor for acquisition of ColRAN bacteraemia. The mortality rates were similar between patients with ColRAN and ColSAN bacteraemia.

Proton pump inhibitor use significantly increases the risk of cryptogenic liver abscess: a population-based study.

BACKGROUND: Proton pump inhibitors (PPIs) increase gastric pH and impair defence mechanisms against ingested pathogens, which may result in the overgrowth of virulent Klebsiella pneumoniae in the intestine and subsequent liver abscess. AIM: We investigated the possible association between PPIs use and cryptogenic liver abscess in Taiwan. METHODS: We conducted a population-based case-control study using data from the National Health Insurance Research Database. A total of 958 adult cases of liver abscess and 3832 age- and sex-matched control patients were enrolled during 2000-2010. Conditional logistic regression was used to estimate the adjusted odds ratios (ORs) in patients using PPIs before cryptogenic liver abscess. RESULTS: The adjusted OR associating current use of PPIs (prescription within the past 30 days) with cryptogenic liver abscess was 4.7 [95% confidence interval (CI), 2.9-7.8], and recent use of PPIs (prescription within the past 31-90 days) with cryptogenic liver abscess was 2.9 (95% CI, 1.4-6.1). A dose-response relationship was apparent for cumulative dose of PPIs within 90 days. Adjusted OR was highest among the patients receiving PPIs more than 60 cumulative defined daily dose (OR = 6.5, 95% CI, 2.8-14.9). CONCLUSION: Proton pump inhibitor therapy within the past 90 days was associated with an increased risk of cryptogenic liver abscess.

Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study.

BACKGROUND: In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections. METHODS: Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections. RESULTS: After a follow-up period of 28 866 person-years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90-2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54-1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin's disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis. CONCLUSION: Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.

Bacteremic nosocomial pneumonia caused by Acinetobacter baumannii and Acinetobacter nosocomialis: a single or two distinct clinical entities?

The phenotypically indistinguishable Acinetobacter baumannii and Acinetobacter nosocomialis have become leading pathogens causing nosocomial pneumonia in critically ill patients. A. baumannii and A. nosocomialis nosocomial pneumonias were grouped as a single clinical entity previously. This study aimed to determine whether they are the same or a different clinical entity. A total of 121 patients with A. baumannii and 131 with A. nosocomialis bacteremic nosocomial pneumonia were included during an 8-year period. Despite the similar Charlson co-morbidity scores at admission, patients with A. baumannii pneumonia were more likely to have abnormal haematological findings, lobar pneumonia, significantly higher Acute Physiology and Chronic Health Evaluation II scores and higher frequency of shock at the onset of bacteraemia than those with A. nosocomialis pneumoni. A. baumannii isolates were resistant to more classes of antimicrobials, except colistin, and therefore the patients with A. baumannii pneumonia were more likely to receive inappropriate antimicrobial therapy. The 14-day mortality was significantly higher in patients with A. baumannii pneumonia (34.7% vs. 15.3%, p 0.001). A. baumannii was an independent risk factor for mortality (OR, 2.03; 95% CI, 1.05-3.90; p 0.035) in the overall cohort after adjustment for other risk factors for death, including inappropriate antimicrobial therapy. The results demonstrated the difference in clinical presentation, microbial characteristics and outcomes between A. baumannii and A. nosocomialis nosocomial pneumonia, and supported that they are two distinct clinical entities.

Impact of Port-A-Cath device management in cancer patients with candidaemia.

This study investigated the impact of management of a totally implantable central venous access port device, Port-A-Cath (Smith Medical, St. Paul, MN, USA), on the outcome of 98 cancer patients with candidaemia. Port-A-Cath retention was found to be significantly associated with poorer outcome, independent of other significant adverse factors [breakthrough candidaemia, Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 21, and worse Eastern Cooperative Oncology Group (ECOG) performance score (3-4)]. However, retention of Port-A-Cath devices could be considered in patients who do not have definite catheter-related candidaemia, are not using total parenteral nutrition, do not have poor ECOG performance scores or APACHE II scores, and do not have septic shock.

Eradication of multidrug-resistant Acinetobacter baumannii from the respiratory tract with inhaled colistin methanesulfonate: a matched case-control study.

Repeated isolation of multidrug-resistant Acinetobacter baumannii (MDRAB) from respiratory secretions poses a great challenge for infection control. We conducted a retrospective case-control study to evaluate the efficacy and adverse effect of inhaled colistin methanesulfonate (CMS) in the eradication of MDRAB from the respiratory tract. Patients who were admitted to Taipei Veterans General Hospital between February 2009 and June 2010, had at least two sets of monomicrobial culture of MDRAB from respiratory secretions, and remained in hospital for at least 14 days after the first isolation of MDRAB (index day) were included. Patients who received intravenous CMS were excluded. Patients who received CMS inhalation for ≥ 3 days were selected as cases whereas the controls were matched for age and Acute Physiology and Chronic Health Evaluation II score. Thirty-nine cases and controls were identified. The duration of CMS inhalation was 10.9 ± 3.6 days. The use of inhaled CMS was the only independent factor associated with the eradication of MDRAB within 14 days after the index day (OR 266.33; 95% CI 11.26-6302.18, p <0.001), and shortened the duration of MDRAB recovery from the respiratory tract by 13.3 ± 1.45 days. The adverse effects were similar for both groups. The increase of colistin minimal inhibitory concentrations in the last isolate compared with the index isolate from the same patient did not differ between the two groups. In conclusion, our study demonstrated that inhaled CMS enhanced the eradication of MDRAB from the respiratory tract without significant clinical adverse effect or impact on colistin resistance.

Clinical characteristics and outcomes of bacteremia due to different genomic species of Acinetobacter baumannii complex in patients with solid tumors.

PURPOSE: Acinetobacter baumannii, Acinetobacter genomic species 3 (AGS 3), and Acinetobacter genomic species sensu Tjernberg and Ursing (AGS 13TU) are phenotypically indistinguishable and are often reported together as the A. baumannii complex (ABC). Few studies have investigated the difference in outcome caused by these different species, and all involved heterogeneous groups of patients. This study aimed to delineate whether there are differences in the clinical characteristics and outcome among patients with solid tumors and bacteremia caused by A. baumannii or two other non-baumannii ABC species (AGS 3 plus AGS 13TU). METHODS: Patients with solid tumors and ABC bacteremia over a period of 5 years in a medical center were identified. The patient data were retrospectively reviewed and analyzed. RESULTS: We identified 103 patients with ABC bacteremia during the study period. Bacteremia was due to A. baumannii in 30 patients, AGS 3 in 24 patients, and AGS 13TU in 49 patients. Among the 103 patients with ABC bacteremia, recent stay in the intensive care unit (ICU) (p = 0.008) was independently associated with the acquisition of A. baumannii bacteremia. Multivariate analysis revealed that bacteremia caused by A. baumannii (hazard ratio [HR] 2.990, 95% confidence interval [CI], 1.021-8.752, p = 0.046) and Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥21 (HR 4.623, 95% CI 1.348-15.859, p = 0.015) were independent factors associated with 14-day mortality. CONCLUSIONS: Infection with A. baumannii and a high APACHE II score (≥21) might be associated with poor outcome in patients with solid tumors and ABC bacteremia.

Changes in the incidence of candidaemia during 2000-2008 in a tertiary medical centre in northern Taiwan.

Candidaemia is associated with high mortality and high healthcare costs. The incidence of candidaemia in Taiwan rose markedly during the period 1980-2000. We conducted this hospital-based surveillance study in order to explore the secular trend in incidence of candidaemia during the period 2000 to 2008. In our study, Candida spp. were the fourth most common cause of bloodstream infections, with a 30-day crude mortality rate of 36.7%. Candida albicans was the most common species identified, although mortality rate did not differ significantly among species. The incidence of candidaemia began to decrease in 2004. Risk factors related to higher mortality included longer hospital stay before onset of candidaemia, liver cirrhosis, malignancy, end-stage renal disease requiring renal dialysis, dependence on mechanical ventilation and urinary catheterisation.

Characteristics of norovirus gastroenteritis outbreaks in a psychiatric centre.

Noroviruses are an important aetiological agent of acute gastroenteritis. They are responsible for large outbreaks of disease in the community, hospitals and long-term-care facilities. The clinical manifestations of norovirus outbreaks in psychiatric units are rarely described. The disease burden and impact highlight the importance of timely notification and investigation of these outbreaks. We analysed the characteristics of four norovirus outbreaks which occurred during a 3-year period in an in-patient psychiatric care unit. A total of 184 patients were affected which included 172 hospitalized patients, seven healthcare workers (HCWs) and five psychiatric nursing-home residents. The mean incidence rate of norovirus gastroenteritis (NVG) in hospitalized patients during these outbreaks was 12·7%. These outbreaks were characterized by higher incidence in middle-aged male patients, predominant sickness of diarrhoea, short duration of illness, peaks in late winter and early spring, and higher susceptibility in acute psychiatric patients. HCWs had longer duration of illness than psychiatric patients. More than 10% of affected patients experienced ≥ 2 infections. Infection control measures were instituted and a comprehensive, responsive standard operating procedure for NVG and outbreak management was developed. After implementation of these measures, no further outbreaks of NVG occurred during the study period.

Clinical and microbiological characteristics of community-acquired thoracic empyema or complicated parapneumonic effusion caused by Klebsiella pneumoniae in Taiwan.

Klebsiella pneumoniae is the major cause of community-acquired pyogenic infections in Taiwan and is becoming an increasing problem in acute thoracic empyema. This study evaluated the clinical and microbiological characteristics of community-acquired thoracic empyema or complicated parapneumonic effusion caused by K. pneumoniae in Taiwanese adults treated during the period 2001-2008 at a tertiary medical center. All clinical isolates were examined for capsular serotypes K1/K2, and pulsed-field gel electrophoresis (PFGE) was performed on strains of the same serotype. K. pneumoniae was the most frequent cause of community-acquired thoracic empyema or complicated parapneumonic effusion. It was associated with high mortality (32.4%) and was an independent risk factor for fatal outcome. Diabetes mellitus, liver cirrhosis, and bronchogenic carcinoma were independent risk factors for K. pneumoniae infection. Serotypes K1 (9/37, 24.3%) and K2 (13/37, 35.1%) were the prevalent strains but did not predispose patients to poor outcome compared with other non-K1/K2 serotypes. There was no major cluster of isolates found among serotype K1/K2 strains. In summary, physicians should be aware of the risk factors for thoracic empyema or complicated parapneumonic effusion caused by K. pneumoniae and the associated high mortality, and monitor these patients more closely.

Adult liver abscess: characteristics of patients living in rural north-eastern Taiwan.

AIMS: This study aimed to analyse the characteristics of adult liver abscess (LA) patients living in rural townships of Taiwan. PATIENTS AND METHODS: We retrospectively screened the electronic admission records of a rural community hospital located in north-eastern Taiwan from 1 April, 2002 to 30 April, 2006. Relevant data, including subjects' basic characteristics, laboratory findings and infectious microorganisms, were extracted. RESULTS: Fifty-six subjects (mean age: 66.1 +/- 15.9 years; range: 23-94 years) were enrolled; one patient had an amoebic LA and 55 had pyogenic LA. Five subjects died in hospital. Overall, 80.5% of patients complained of having a fever, 87.5% had single abscess, 71.4% had right hepatic lobe involvement and 58.9% underwent invasive drainage. Most subjects (66.1%) did not have diabetes mellitus, 94.6% did not have a hepato-biliary tumour, 73.2% did not have gallstones, 78.6% did not have hepatitis and 87.5% did not have prior hepato-biliary surgery. Klebsiella pneumoniae was the most common infecting microorganism. Previous hepato-biliary surgery and serum creatinine >2.0 mg/dl were significantly more common in patients >or=65 years of age (p = 0.031). Diabetes mellitus was more common in female subjects (p = 0.021). Invasive drainage and single abscess were not significantly correlated to prognosis. DISCUSSION: Adult LA patients living in rural north-eastern Taiwan have different characteristics than patients living in urban areas. Geriatric LA patients should be managed cautiously because of the possibility of renal insufficiency or previous hepato-biliary surgery. Female LA patients should be evaluated for the presence of diabetes mellitus.

Dissemination of multidrug-resistant, class 1 integron-carrying Acinetobacter baumannii isolates in Taiwan.

In this study, 283 multidrug-resistant Acinetobacter baumannii (MDR-AB) bloodstream isolates were collected between 1996 and 2004, from three teaching hospitals located in different regions of Taiwan. Susceptibility data showed that strains carrying class 1 integrons were significantly more resistant (p <0.01) to all tested antibiotics (except aztreonam and chloramphenicol) than strains lacking integrons, Seven types of gene cassette were identified among these strains, including two that have not been previously reported. The vast majority of the cassettes encoded aminoglycoside resistance genes, including aacA4, aacC1, aac(6')-II, aadA1, aadA2, aadA4 and aadDA1. Sixteen distinct ribotypes were identified in MDR-AB isolates carrying class 1 integrons. Only one strain was found to produce an extended-spectrum beta-lactamase, i.e. VEB-3. In the 18 imipenem-resistant strains, two carbapenenmase genes, bla(VIM-11) and bla(OXA-58), were found concomitantly in one isolate. An island-wide epidemic clone and an endemic clone from a hospital located in the northern region were identified by ribotyping. On the basis of the susceptibility data among the different ribogroups, the epidemic clone was associated more significantly with resistance to cefepime and ampicillin-sulbactam than was the endemic clone. In conclusion, the presence of class 1 integrons was significantly associated with resistance in MDR-AB, and the epidemic, class 1 integron-carrying MDR-AB clone was found to be widespread in Taiwan.

Comparison of one-tube multiplex PCR, automated ribotyping and intergenic spacer (ITS) sequencing for rapid identification of Acinetobacter baumannii.

Acinetobacter baumannii has emerged as a serious cause of nosocomial infections. Rapid identification of this pathogen is required so that appropriate therapy can be given and outbreaks controlled. This study evaluated a multiplex PCR and an automated ribotyping system for the rapid identification of Acinetobacter baumannii. In total, 22 different reference strains and 138 clinical isolates of Acinetobacter spp., identified by 16S-23S rRNA intergenic spacer (ITS) sequence analysis, were evaluated. All A. baumannii isolates (82 clinical isolates and one reference strain) were identified by the multiplex PCR method (specificity 100%). The sensitivity and specificity of the ribotyping system for identification of A. baumannii were 85.5% (71/83) and 93.5% (72/77), respectively. An additional 100 clinical isolates belonging to the Acinetobacter calcoaceticus-A. baumannii complex were used to compare these two methods for identification of A. baumannii, and this comparison revealed a level of disagreement of 14% (14 isolates). The accuracy of the multiplex PCR was 100%, which was confirmed by sequence analysis of the ITS and recA gene of these isolates. Thus, the multiplex PCR method dramatically increased the efficiency and speed of A. baumannii identification.

In vitro susceptibility of six fluoroquinolones against invasive Streptococcus pneumoniae isolated from 1996 to 2001 in Taiwan.

A total of 331 invasive nonduplicated Streptococcus pneumoniae isolates from three sampling periods during 1996 to 2001 were tested for susceptibility to recently developed fluoroquinolones. Five major serotypes, 23F, 6B, 14, 19F, and 3, were frequently encountered in this collection. Penicillin nonsusceptible isolates constituted 52.9% from 1996 to 1997, 61.6% from 1998 to 1999, and 60.0% from 2000 to 2001. Fifty-seven percent of the isolates were susceptible to cefotaxime, 56.5% to ceftriaxone, 54.1% to cefepime, and 52.6% to cefuroxime. Macrolide-susceptible isolates constituted less than 14% of the total sample, and no vancomycin-resistant isolates were detected. For fluoroquinolones, MIC90 was lowest for gemifloxacin (MIC90 = < or = 0.12 microg/ml), followed by moxifloxacin (MIC90 = 0.25 microg/ml), gatifloxacin (MIC90 = 0.5 microg/ml), sparfloxacin (MIC90 = 0.5 microg/ml), levofloxacin (MIC90 = 1 microg/ml), and ciprofloxacin (MIC90 = 2 microg/ml). All isolates were susceptible to sparfloxacin, levofloxacin, gatifloxacin, and gemifloxacin apart from one isolate (0.3%), which was simultaneously resistant to sparfloxacin, levofloxacin, and gatifloxacin. Mutations at the positions S81F of GyrA and D435N and I460V of ParC were detected for this multiple drug resistant isolate. The in vitro results suggest that recently developed fluoroquinolones are very effective against invasive S. pneumoniae isolates in Taiwan. Nevertheless, emerging fluoroquinolone resistance should be acknowledged and clinicians alerted. Surveillance should be carried out to monitor any changes in antibiotic resistance of S. pneumoniae.

The assessment of stability and reliability of a virtual reality-based laparoscopic gynecology simulation system.

PURPOSE OF INVESTIGATION: Surgeons require practiced skills in laparoscopic surgery. A virtual reality-based simulator system was developed for extensive training. The purpose of this study was to assess the feasibility of a virtual reality-based laparoscopic gynecology simulation system. METHODS: Laparoscopic tools and three-dimensional virtual environments were included in the simulation system. Ten healthy, non-disabled volunteers were recruited. The surgical procedure is a process of tubal sterilization by cauterization. Volunteers followed the training procedure, 15 trials in the first test and retest, respectively. RESULTS: Stable performances were obtained after about seven trials for all subjects. The intraclass correlation coefficients were 0.935 and 0.425 for task time and error frequency, respectively. CONCLUSION: The results of this study indicate that the system is stable and has a fair high test-retest reliability. Therefore, the VR-based laparoscopic gynecology system is feasible.

A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis?

BACKGROUND AND AIMS: Over the past two decades in Taiwan, pyogenic liver abscess has usually been caused by a single microorganism, Klebsiella pneumoniae, and is frequently associated with the serious complication of endophthalmitis, especially in diabetic patients. However, the relationship between the clinical presentation and bacterial factors remains unclear. The aim of this study was to investigate the clinical features of patients and the serotype and ribotype of K pneumoniae liver abscess. METHODS: From July 1991 to June 1998, a total of 134 cases of K pneumoniae liver abscess with 248 K pneumoniae isolates from the same patients were collected from two large medical centres in northern Taiwan. Clinical data were collected from medical records. Serotyping and ribotyping were performed using the countercurrent immunoelectrophoresis method and automated Riboprinter. RESULTS: Serotyping revealed that the most common serotypes were K1 (63.4%) and K2 (14.2%). K1 isolates occurred at a significantly higher frequency (p<0.01) than all other serotypes. Among 134 patients, 105 (78.4%) had suffered from diabetes mellitus for 3-15 years. Fourteen patients (10.4%) had metastatic infection to the eye causing septic endophthalmitis. Liver aspirates, and blood and vitreous pus cultures yielded the same serotype of K pneumoniae in all patients. Among patients with septic endophthalmitis, 92.3% (13/14) were diabetic, and 85.7% (12/14) of the isolates belonged to serotype K1. For molecular typing, different degrees of genetic polymorphism among isolates with the same K1 serotype suggested no particular prevalence of any one strain in K pneumoniae liver abscess. CONCLUSION: K pneumoniae serotype K1 was significantly associated with liver abscess and the complication of endophthalmitis, especially in diabetic patients. Physicians should request an immediate report of serotyping and susceptibility test results simultaneously if a diagnosis of pyogenic liver abscess has been made so that early and appropriate management for possible complications will not be delayed. The use of ceftriaxone because of its higher concentration in the aqueous humor is suggested to decrease the chance of septic endophthalmitis.

Comparative study of ceftibuten and cefixime in the treatment of complicated urinary tract infections.

Between August 1996 and May 1998, a total of 62 patients who had complicated urinary tract infections treated at the Taipei Veterans General Hospital were enrolled into this study. This prospective, randomized, open-labeled trial aimed at comparing the efficacy and safety of ceftibuten and cefixime, prescribed each at a dose of 200 mg twice daily, in treating complicated urinary tract infection. Seventeen patients were later excluded from the analysis because of resistant pathogens (7 patients), uncomplicated urinary tract infection (6), initial culture negative for bacteria (3), and infective endocarditis (1). The remaining 45 patients were categorized into ceftibuten (n=23; mean age, 71.3 years) and cefixime (n=22; mean age, 62.8 years) treatment groups. No significant difference in demographic data and clinical characteristics was found between the 2 groups. The clinical efficacy rate (78.3% vs 77.3%, p=0.9) and bacteriological eradication rate (52.2% vs 63.6%, p=0.08) were similar between the ceftibuten and the cefixime group. Adverse effects caused by ceftibuten treatment included diarrhea and slight elevation of the serum level of liver transaminase in 2 (6.5%) patients. Those caused by cefixime treatment included slight elevation of serum level of liver transaminase in 2 (6.5%) patients and skin rash in 1 (3.2%) patient. All of these adverse effects resolved quickly after the regimen had been completed, and no patient discontinued the regimen because of the adverse effects. The results suggest that oral administration of ceftibuten 200 mg twice daily is as effective and safe as oral administration of cefixime 200 mg twice daily in the treatment of complicated urinary tract infections.

Characteristics of patients with Burkholderia cepacia bacteremia.

Burkholderia cepacia has become an important pathogen of infections in immunocompromised and nosocomial patients. The characteristics of 42 episodes of B. cepacia bacteremia in 40 patients admitted to the Taipei Veterans General Hospital between January 1997 and December 1999 were retrospectively analyzed. Factors that adversely influenced the mortality rate included respiratory failure, an unknown infection source, a period in an intensive care unit, and shock. Most of the patients had serious underlying diseases, such as diabetes mellitus, malignancy, congestive heart failure, and chronic obstructive pulmonary disease. The mean time for a positive blood culture was 45 days after admission. The overall mortality rate was 28.6% (12/42), and 44.4% (12/27) of all deaths were directly related to B. cepacia bacteremia. Polymicrobial bacteremia was found in 5 patients. Ceftazidime was the most effective antimicrobial agent in vitro, whereas chloramphenicol, imipenem, and trimethoprim/sulfamethoxazole were less effective alternatives. Appropriate antibiotic therapy was given to 30 patients, most of whom responded to the therapy except for 5 who died despite receiving appropriate treatment. Although B. cepacia infection develops in a relatively small proportion of hospitalized individuals, it has a major impact on morbidity and mortality. In view of the fact that B. cepacia develops resistance to a wide range of antimicrobial agents, ceftazidime and/or trimethoprim/sulfamethoxazole should be the drug of choice for empiric therapy.

Diversity of SHV and TEM beta-lactamases in Klebsiella pneumoniae: gene evolution in Northern Taiwan and two novel beta-lactamases, SHV-25 and SHV-26.

A total of 113 blood culture isolates of Klebsiella pneumoniae from 10 hospitals in northern Taiwan were studied for SHV and TEM beta-lactamase production. bla(SHV) was amplified from all isolates by PCR. TEM-type resistance, was found in 32 of the isolates and was of the TEM-1 type in all isolates. SHV-1, -2, -5, -11, and -12 and two novel enzymes were identified. These novel enzymes were designated SHV-25 and SHV-26 and had pIs of 7.5 and 7.6, respectively. Amino acid differences in comparison to the amino acid sequence of bla(SHV-1) were found at positions T18A (ThrACC-->AlaGCC), L35Q (LeuCTA-->GluCAA), and M129V (MetATG-->ValGTG) for SHV-25 and at position A187T (AlaGCC-->ThrACC) for SHV-26. The results of substrate profiles and MIC determinations showed that the novel enzymes did not hydrolyze extended-spectrum cephalosporins, rendering the isolates susceptible to these agents. Inhibition profiles revealed that the 50% inhibitory concentration for SHV-26 was higher than those for SHV-1 and SHV-25, resulting in an intermediate resistance to amoxicillin-clavulanic acid. Forty-nine ribotypes were identified, suggesting that major clonal spread had not occurred in any of the hospitals. According to the amino acid sequence, SHV beta-lactamases in Taiwan may basically be derived through stepwise mutation from SHV-1 or SHV-11 and further subdivided by four routes. The stepwise mutations initiated from SHV-1 or SHV-11 to SHV-2, SHV-5, and SHV-12 comprise the evolutionary change responsible for extended-spectrum beta-lactamase (ESBL) production in Taiwan. The stepwise mutations that lead to a non-ESBL (SHV-25) and the beta-lactamase (SHV-26) with reduced susceptibility to clavulanic acid are possibly derived from SHV-11 and SHV-1, respectively. The results suggest a stepwise evolution of SHV beta-lactamases in Taiwan.

Investigation of an outbreak caused by methicillin-resistant Staphylococcus aureus in a cardiovascular surgery unit by ribotyping, randomly amplifed polymorphic DNA and pulsed-field gel electrophoresis.

An outbreak caused by rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) in an intensive care unit for cardiovascular surgery was investigated by phenotypic and genotypic methods. Fourteen isolates were collected during a 2-month period from clinical and environmental specimens in the unit recently re-opened after reconstruction. The isolates were tested for antibiotic susceptibility patterns and genotyped by automated ribotyping, randomly amplified polymorphic DNA-PCR (RAPD) analysis and pulsed-field gel electrophoresis (PFGE). Automated ribotyping applying EcoRI digestion proved to be of no value in separating the isolates. In contrast, PFGE grouped the isolates into four clusters different from the reference strain. These results fully correlated with the antibiograms. Twelve of the isolates were grouped into two clonally related clusters. RAPD analyses grouped the isolates into five clusters. Except for two isolates of one patient, which had different RAPD patterns, PFGE and RAPD analyses presented very similar results. The results verified the usefulness of PFGE in studies of MRSA epidemics. A combination of these two methods reduces the time to identification of an outbreak and increases the accuracy in detection of intraspecies differences.