Antibiotic research and development: business as usual?

The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public–private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents

Short-term Treatment of Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis of the Effect of Acid-suppressant Drugs in Empirical Treatment and in Endoscopy-negative Patients

OBJECTIVE: To investigate the efficacy of acid suppressant drugs in the empirical treatment of gastroesophageal reflux disease (GERD) and in the treatment of endoscopy-negative reflux disease (ENRD). DESIGN: medline, embase, and the Cochrane Controlled Trials Register were searched. Bibliographies were reviewed. SETTING: Studies were eligible that compared the short-term use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H(2)RAs) with each other or with placebo in adults with GERD who were enrolled irrespective of endoscopic findings (empirical cases) or in whom endoscopy showed no signs of esophagitis (endoscopy-negative cases). MEASUREMENTS: Of 1,408 studies, only 13 could be included for meta-analysis. Data on 3,433 patients empirically treated for GERD and 2,520 patients treated for ENRD were extracted. The primary endpoint was relief of heartburn. MAIN RESULTS: In the empirical treatment of GERD, the summary relative risk (sRR) for symptom relief from H(2)RAs versus placebo was 0.77 (95% confidence interval [95% CI], 0.60 to 0.99). RR in the only placebo-controlled PPI trial was 0.35 (95% CI, 0.26 to 0.46). The sRR for standard dose PPIs versus H(2)RAs was 0.55 (95% CI, 0.44 to 0.68). In treatment of ENRD, both PPIs (sRR, 0.64; 95% CI, 0.52 to 0.79) and H(2)RAs (sRR, 0.78; 95% CI, 0.62 to 0.97) were superior to placebo, and PPIs were superior to H(2)RAs (sRR, 0.81; 95% CI, 0.70 to 0.95). CONCLUSIONS: Acid suppressant therapy (with a PPI or an H(2)RA) is more effective than placebo for short-term relief of heartburn in patients with persistent symptoms who are treated empirically for GERD and in those in whom esophagitis was excluded after endoscopy. The benefit of PPIs compared with H(2)RAs is more pronounced in patients treated empirically

Current management strategies and emerging treatments for functional dyspepsia.

Functional dyspepsia refers to painful and nonpainful symptoms that are perceived to arise in the upper digestive tract but are not secondary to organic, systemic or metabolic diseases. The symptoms of this syndrome often overlap with those of GERD and IBS, making its management far from simple. If Helicobacter pylori infection is diagnosed in patients with functional dyspepsia, it should be treated. In patients with mild or intermittent symptoms, reassurance and lifestyle advice might be sufficient; in patients not responding to these measures, or in those with more severe symptoms, drug therapy should be considered. Both PPIs and prokinetics can be used in initial empirical pharmacotherapy based on symptom patterns--a PPI is more likely to be effective in the presence of retrosternal or epigastric burning or epigastric pain, whereas a prokinetic is more effective in dyspepsia with early satiation or postprandial fullness. Although combinations of PPIs and prokinetics might have additive symptomatic effects, single-drug therapy is initially preferable. Antidepressants or referral to a psychiatrist or psychotherapist can be considered in nonresponders and in those whose symptoms have a marked effect on daily functioning. Despite extensive research, functional dyspepsia treatment often remains unsatisfactory. Better characterization of dyspeptic subgroups and understanding of underlying mechanisms will enable treatment advances to be made in the future