traT gene sequences, serum resistance and pathogenicity-related factors in clinical isolates of Escherichia coli and other gram-negative bacteria

The R6-5 plasmid-specified outer membrane protein, TraT protein, has previously been shown to mediate resistance to bacterial killing by serum. Colony hybridization with a 700 bp DNA fragment carrying most of the traT gene was used to examine the prevalence of traT in Gram-negative bacteria, particularly strains of Escherichia coli, isolated from clinical specimens. traT was found in isolates of E. coli, Salmonella, Shigella and Klebsiella, but not in Pseudomonas, Aeromonas or Plesiomonas, nor in the few isolates of Enterobacter, Proteus, Acinetobacter, Citrobacter, Serratia or Yersinia that were examined. It was detected in a significantly higher proportion of the E. coli strains isolated from the blood of patients with bacteraemia/septicaemia or from faeces of patients with enteric infections (50-70%) than in that of strains isolated from normal faeces (20-40%). The incidence of traT in strains isolated from cases of urinary tract infections was variable. traT was found to be frequently associated with production of the K1 capsule and with the carriage of ColV plasmids, but not with the carriage of R plasmids, nor with serum resistance or the production of haemolysin

Correction: Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

BACKGROUND: Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations. METHODS: Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up. RESULTS: At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%). CONCLUSIONS: Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov)

Utility of MELD and Child-Turcotte-Pugh Scores and the Canadian Waitlisting Algorithm in Predicting Short-term Survival after Liver Transplant

BACKGROUND: The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores are important predictors for survival after liver transplantation (LT). The objective of this study was to compare the utility of MELD and CTP scores with Canadian waitlisting algorithm in transplantation (CanWAIT) status for predicting 90-day survival after LT. METHODS: Retrospectively, we analyzed all 228 liver transplants performed in adults by the Atlantic Liver Transplant Program since 1985. These cases included combined transplants, retransplants and those after fulminant liver failure. MELD and CTP scores were calculated, and CanWAIT status and waiting time on the day of LT determined. We used c-statistic for 90-day outcome as the endpoint (survival), comparing areas under the receiver operating characteristic (ROC) curves for MELD and CTP scores and CanWAIT status. RESULTS: Mean (and standard deviation [SD]) MELD score was 18 (SD 12); CTP score, 10 (SD 3); and waiting time, 97 (SD 132) days. At the time of LT, 54% were in CanWAIT status 1; 4% in 1T; 14% in 2; 11% in 3; 6% in 3F; 4% in 4; and 7% in status 4F. Overall 90-day survival was 80% (95% confidence interval [CI] 75%-85%), exceeding the predicted survival by MELD scale with transplant of only 51% (CI 47%-55%). By c-statistic, CanWAIT is a clinically relevant predictor of 90-day outcomes in LT. By multivariate regression analysis, only CanWAIT status and age were found to have independent associations for short-term outcomes after LT. INTERPRETATION: CanWAIT status stratifies LT patients better and predicts short-term outcome more accurately than MELD or CTP scores, and so should not be replaced by MELD or CTP scores. This observation should be confirmed by a prospective and multicentre study in Canada