Effect of Postprandial Administration of Esomeprazole on Reflux Symptoms in Gastroesophageal Reflux Disease: A Randomized, Controlled Trial.

BACKGROUND: Esomeprazole is commonly administered with food; however, clinical data to support this practice are lacking. We aimed to determine the effect of postprandial ingestion of esomeprazole on reflux symptoms among patients with gastroesophageal reflux disease (GERD). METHODS: Consecutive patients with GERD adequately controlled with esomeprazole 40 mg daily, entered a 2-week lead-in period during which esomeprazole was administered 30 min before breakfast. Patients were then randomized to continue preprandial ingestion or to ingest esomeprazole following a standardized meal. Outcomes included GERD frequency and severity indices, GERD-health-related quality of life (GERD-HRQL) questionnaire and Short Form 36 (SF-36). RESULTS: Thirty-two patients (17 [53.1%] men, aged 53.5 ± 17.2 years) were included, and 16 (50%) switched to postprandial ingestion of esomeprazole. GERD frequency and severity decreased in both groups (Δ9.0 ± 7.2 vs. Δ10.0 ± 8.1, p = 0.29; Δ6.6 ± 6.8 vs. Δ10.2 ± 7.4, p = 0.57 in postprandial group vs. controls, for frequency and severity, respectively). GERD-HRQL improved in both study groups to a similar degree (Δ10.7 ± 10.5 vs. Δ10.0 ± 13.8, p = 0.97). All SF-36 subscores increased in both groups to a similar degree. In a mixed linear model, there were no differences between the study groups in the changes observed in GERD frequency (p = 0.49), severity (p = 0.32), and GERD-HRQL (p = 0.98) during the study period. CONCLUSION: Switching to postprandial administration of esomeprazole is not associated with deterioration in reflux symptoms among patients with GERD. Esomeprazole seems to remain efficacious when administered after meals.

Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: To document the effects of appropriate and inappropriate empirical antibiotic therapy on mortality in a cohort of patients with bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA) and to summarize effects with previous studies. METHODS: In the retrospective cohort study, episodes of clinically significant MRSA bacteraemia during a 15 year period were included. Polymicrobial episodes were excluded unless MRSA was isolated in more than one bottle and co-pathogens were given appropriate empirical antibiotic treatment. Appropriate empirical treatment was defined as matching in vitro susceptibility and started within 48 h of blood-culture taking, except for single aminoglycosides or rifampicin. We assessed univariate and multivariate associations between appropriate empirical therapy and 30 day all-cause mortality. Multivariable analysis was conducted using backward stepwise logistic regression. We reviewed all studies assessing the effects of appropriate empirical antibiotic treatment on mortality for MRSA infections and compiled adjusted odds ratios (ORs) using a random effects meta-analysis. RESULTS: Five hundred and ten episodes of MRSA bacteraemia were included. There were no cases of community-acquired infection. The 30 day mortality was 43.9% (224/510) and was stable throughout the study period. Mortality was significantly higher among patients receiving inappropriate (168/342, 49.1%) compared with those receiving appropriate (56/168, 33.3%) empirical antibiotic treatment, P = 0.001. In the adjusted analysis the OR was 2.15 [95% confidence interval (CI) 1.34-3.46]. Pooling of six studies using adequate methodology for the adjusted analysis resulted in an OR of 1.98 (95% CI 1.62-2.44). CONCLUSIONS: Appropriate empirical antibiotic treatment has a significant survival benefit in MRSA bacteraemia. Treatment guidelines should consider this benefit.

Co-trimoxazole versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteraemia: a retrospective cohort study.

OBJECTIVES: To evaluate the efficacy and safety of co-trimoxazole versus that of vancomycin in adults with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. PATIENTS AND METHODS: Retrospective matched cohort study. Thirty-eight patients with MRSA bacteraemia, treated with co-trimoxazole as the main therapeutic agent, were matched with 76 patients treated with vancomycin as the main agent. The groups were matched for age, sex, functional status, endovascular source of infection, appropriateness of empirical antibiotic therapy, presence of a foreign body, sepsis severity and Charlson score. The outcomes collected were 30 day mortality, persistent bacteraemia [defined as positive blood culture (BC) >14 days after the first positive BC, but within 30 days], relapse (defined as recurrence of the same phenotype >30 days after the first positive BC within 12 months) and adverse events. RESULTS: The groups were well matched. Thirty day mortality was not significantly different between the groups [co-trimoxazole 13/38 (34.2%); vancomycin 31/76 (40.8%); odds ratio 0.76, 95% confidence interval 0.34-1.7]. There was only one case of relapse in the co-trimoxazole group (2.6%) compared with nine cases in the vancomycin group (11.8%). Incidence of relapse or persistent bacteraemia was lower in the co-trimoxazole group (3/38, 7.9%) than in the vancomycin group (13/76, 17.1%), although the difference was not statistically significant (P = 0.182). Development of renal failure was similar [co-trimoxazole 11/38 (28.9%); vancomycin 21/76 (27.6%)]. CONCLUSIONS: Within the limitations of a small retrospective study, co-trimoxazole had a safety and efficacy profile similar to that of vancomycin and may offer an attractive additional therapeutic option for MRSA bacteraemia. A prospective, randomized controlled trial is warranted.

Effectiveness and safety of colistin: prospective comparative cohort study.

BACKGROUND: Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics. METHODS: This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported. RESULTS: Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08-2.31). In the adjusted analysis the OR was 1.44 (0.91-2.26) overall and 1.99 (1.06-3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01-1.60) overall and 1.65 (1.18-2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54-7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up. CONCLUSIONS: The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than beta-lactam antibiotics.