FDA advisory panel recommends new antibiotic for approval
An advisory panel to the US Food and Drug Administration (FDA) voted on Nov 3 to recommend a new antibiotic to treat community-acquired pneumonia (CABP), despite concerns over liver toxicity.
In a 7-6 vote, members of the FDA's Antimicrobial Drugs Advisory Committee recommended approval of the drug solithromycin, a macrolide antibiotic that has activity against macrolide-resistant CABP pathogens. But while the panel voted unanimously (13-0) that there was substantial evidence of solithromycin's efficacy, and that the drug works as well as moxifloxacin in patients with CABP, they also voted 12-1 that the risk of hepatoxicity has not been adequately characterized.
Reuters reports that clinical trials of solithromycin showed greater number of patients taking the drug developed elevated liver enzymes than those taking moxifloxacin, a possible sign of underlying liver damage. But there were no cases of acute liver injury. The panel recommended that drug maker Cempra Inc. be required to conduct additional studies on potential liver damage after the drug is approved.
"We appreciate the meaningful discussion from today's panel. Their supportive view and thoughtful comments on approaches to ensuring appropriate use are consistent with Cempra’s commitment to make solithromycin available to the right patients for a five to seven day course of an oral and/or IV macrolide as monotherapy for CABP," Cempra president and CEO Prabhavathi Fernandes PhD, said in a company press release.
Cempra argues that new antibiotics for the treatment of CABP are much needed, as rates of pneumococcal resistance to macrolides can exceed 50%.
Study finds limiting use of '4C' antibiotics can reduce C diff infection rates
A new study out of Scotland suggests that limiting the use of antibiotics associated with Clostridium difficile infection risk can reduce C difficile infection rates in hospital and community populations.
The study, published Nov 4 in the Lancet Infectious Diseases, was an observational and quasi-experimental time-series analysis that aimed to measure the impact of an antibiotic stewardship program (ASP) in northeast Scotland that emphasized reduction in hospital and community use of antibiotics linked to C difficile infection. The antibiotics—known as the 4Cs—included ciprofloxacin/fluoroquinolones, co-amoxiclav, clindamycin, and cephalosporins. After implementation, use of the 4C antibiotics was reduced by 50% in hospitals and the community.
Other infection control and prevention measures in the ASP included a hand-hygiene campaign, national auditing and inspections of hospital environment cleanliness, and reduced inappropriate use of proton-pump inhibitors. The total effect of interventions, which were initiated in 2009, was defined as the difference between the C difficile infection burden with the ASP and projected scenarios without stewardship.
From 1997 to 2012, investigators identified 4,885 cases of hospital-onset C difficile and 1,625 cases of community-onset C difficile. Controlling for multiple cofounders, the authors estimated that after implementation of the ASP, C difficile infection prevalence fell by 68% in hospitals and 45% in the community compared to projected scenarios without the ASP. Further analysis indicated that declines in C difficile could be explained by the removal of antibiotic selection pressure favoring multidrug-resistant ribotypes R001 and R027, which have been associated with higher incidence and more severe disease. No significant effects from other measures of the ASP were identified.
"Our study adds to existing evidence that antibiotic stewardship might be an effective tool for the control of C difficile infection in both hospitals and the community," the authors wrote.
Nov 4 Lancet Infect Dis study
Nov 4 Lancet Infect Dis commentary