SummaryBackgroundStaphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.MethodsIn this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.FindingsBetween Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).InterpretationAdjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FundingUK National Institute for Health Research Health Technology Assessment.

The study investigated the oral absorption of two antifungal agents, fluconazole and itraconazole, under conditions of low intragastric acidity. Twelve healthy male volunteers received each of 4 dosing regimens : 200 mg itraconazole alone, 200 mg itraconazole and famotidine, 100 mg fluconazole alone, and 100 mg fluconazole and farnotidine. Two oral doses of 40 mg famotidine were used to induce hypochlorhydria.Serum drug concentrations were measured (by high pressure liquid chromatography) for 48 h after a single dose of each anti-fungal agent. When dosed with famotidine, there was a significant 52.9 % decrease of the peak intraconazole concentration (P < 0.01 l), and a significant 5 1.1 % decrease of the 48-h integrated serum intraconazole concentration (P = 0.005). Famotidine-induced hypochlorhydria did not affect the absorption of fluconazole.

Rabeprazole 10, 20 and 40 mg produce significant, profound dose-related inhibition of gastric acid secretion. Taking into account reciprocal increases in plasma gastrin and the interindividual variation in antisecretory response, 20 mg appears to be the preferred dose for routine clinical use.

Background: Dual therapy with ranitidine bismuth citrate plus clarithromycin twice daily for 14 days is an effective regimen for eradicating Helicobacter pylori infection. Aim: To determine whether this regimen can be improved by the addition of a second antibiotic, tetracycline hydrochloride, whilst reducing the duration of treatment to 7 days. Methods: Sixty‐one out‐patients were enrolled to this open treatment study. All had H. pylori infection, as determined by 13C‐urea breath test and, for those undergoing endoscopy, by rapid urease test. Patients were treated with ranitidine bismuth citrate 400 mg, clarithromycin 500 mg and tetracycline hydrochloride 500 mg all twice daily for 7 days. Eradication of H.␣pylori was assessed by two separate 13C‐urea breath tests, the first 28–68 days after the completion of treatment, the second 28–162 days later. H. pylori infection was considered cured if both tests were negative. Results: All 61 patients were included in the intention‐to‐treat efficacy analysis. Successful eradication of H.␣pylori was achieved in 55/61 patients (90 %; 95% CI: 82–98%). Fifty‐nine out of sixty‐one patients reported 100% compliance; one patient missed a single dose of medication and the other withdrew at 48 h due to nausea and vomiting. Minor adverse events were reported by 30/61 patients. Conclusion: One‐week triple therapy with ranitidine bismuth citrate, clarithromycin and tetracycline, all twice daily, is a safe and well‐tolerated regimen which eradicates H. pylori in 90% of infected patients.

The Royal Free Hospital protocol for simultaneous measurement of 24-hour intragastric acidity and plasma gastrin concentration is described in detail. The methods of analysing such data are discussed, with recommendations for a standard four-way analysis: median hourly 24-hour intragastric acidity or pH, or plasma gastrin concentration; integrated 24-hour intragastric acidity, or plasma gastrin concentration; analysis of integrated values according to meal-related intervals; and quantification of the percentage of time in a 24-hour period that intragastric pH is greater than 3.