WHO ranks antibiotics for stewardship efforts
Originally published Jul 21.
Carbapenems, penicillins, quinolones, macrolides and ketolides, and the newest cephalosporins were among the antibiotics that a World Health Organization (WHO) expert panel yesterday rated as "critically important" for human medicine of highest priority in limiting their use in food animals to combat resistance to the drugs.
The WHO advisory group's latest update of the list appeared in Clinical Infectious Diseases. It was first developed in 2005 and updated about every 2 year since then, most recently in 2013.
"The updated ranking allows stakeholders in the agriculture sector and regulatory agencies to focus risk management efforts on drugs used in food animals that are the most important to human medicine," the authors said.
"In particular, the current large scale use of fluoroquinolones, macrolides, third generation cephalosporins and any potential use of glycopeptides and carbapenems needs to be addressed urgently."
The complete list of antibiotics deemed critical to human health is: aminoglycosides, ansamycins, carbapenems and other penems, third- and fourth-generation cephalosporins, phosphonic acid derivatives, glycopeptides, glycylcyclines, lipopeptides, macrolides and ketolides, monobactams, oxazolidinones, penicillins (natural, aminopenicillins, and antipseudomonal), polymyxins, quinolones, and drugs solely used to treat tuberculosis and other mycobacterial diseases.
Phosphonic acid derivatives, monobactams, and polymyxins are new to the list because of their greater importance for treating multi-resistant gram-negative bacteria. Streptogramins, on the other hand, were bumped from the critically important list to the next level—highly important—because more effective antimicrobials with fewer side effects are now available to treat gram-positive infections, the experts said.
Jul 20 Clin Infect Dis abstract
New antibiotic performs well against hospital pneumonia in phase 3 trial
Originally published Jul 21.
London-based drug company AstraZeneca today announced that Zavicefta, its new combination antibiotic for treating a spectrum of serious gram-negative infections, performed well in a phase 3 trial against hospital-acquired pneumonia (HAP), including infections tied to ventilator use.
The intravenous drug is a combination of third-generation cephalosporin drug ceftazidime and the broad-spectrum beta-lactamase inhibitor avibactam. It was found to be statistically non-inferior to meropenem, a carbapenem antibiotic, in the REPROVE trial, which involved 879 HAP patients in 23 countries, the company said in a news release. Results were comparable between the two drugs for both cure rates at 21 days and all-cause mortality at 28 days.
Safety profiles were similar for both Zavicefta and meropenem. Full results from the REPROVE trial are expected to be presented at future scientific meetings, the company said.
Hans Sijbesma, managing director of AstraZeneca's Antibiotics Business Unit, said, "The positive results from this important phase 3 trial validate our science-led approach and confirm the effectiveness of Zavicefta in treating hospital-acquired pneumonia, providing patients and physicians with a much-needed new treatment option in the fight against antibiotic-resistant pathogens."
The European Commission approved the drug on Jun 24 for intravenous use in treating adults who have HAP.
Jul 21 AstraZeneca press release
Algorithm may help identify drugs to treat resistant fungal infections
Originally published Jul 14.
A team of Chinese scientists has developed an algorithm that can identify drug combinations to treat drug-resistant fungal infections.
In a study published today in PLoS Computational Biology, the researchers report that they have developed a novel algorithm—called Network-based Laplacian regularized Least Square Synergistic (NLLSS) drug combination prediction—that successfully identified 7 of 13 synergistic drug combinations to treat the fungal pathogen Candida albicans. The algorithm, which was experimentally confirmed, works by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures.
According to the study, fungal infections are one of the leading causes of hospital-acquired infections and are associated with high mortality, especially in patients with weakened immune systems. Moreover, drug resistance is becoming increasingly common in fungal infections. But synergistic drug combinations—in which the combination of two agents increases the effectiveness of a drug—have become a promising avenue of treatment for drug-resistant infections, the authors said.
The problem, however, is that effective drug combinations have traditionally been identified through screening all possible combinations of a pre-defined set of drugs, which is a timely, costly, and labor-intensive process. Developing an algorithm that can computationally screen and identify synergistic drug combinations to treat drug-resistant fungal infections, the authors said, could save time and money and provide new treatments for overcoming fungal resistance.
Jul 14 PLoS Comput Biol study