A New Drug against Multi-Resistant Bacteria

A study led by Dr. Jordi Vila, researcher at ISGlobal, shows that a new combination of an antibiotic (ceftazidime) with a beta-lactamase inhibitor has potent activity against multi-resistant bacterial strains, including those that are resistant to fluoroquinolones. The study, published in the Antimicrobial Agents and Chemotherapy journal, concludes that fluoroquinolone resistance does not affect bacterial susceptibility to ceftazidime-avibactim; in other words, there is no cross-resistance.

Avibactam is a new non-beta-lactam compound that inhibits the activity of bacterial enzymes called beta-lactamases of type A, C and some D. These enzymes confer resistance to beta-lactam antibiotics, and the prevalence of bacteria expressing them is increasing worldwide. They cause hospital-associated infections and are resistant to many types of antibiotics, including fluoroquinolones. The aim of this study was to evaluate the activity of ceftazidime-avibactam against multi-resistant bacteria. The authors analyzed Enterobacterial and Pseudomonas aeruginosa strains isolated from infected patients, as well as fluoroquinolone-resistant mutants generated in the laboratory. They found that the ceftazidime-avibactam combination has potent in vitro activity against fluoroquinolone-resistant bacteria, including those that express an extended spectrum of beta lactamases. "The absence of cross-resistance is good news" says Dr. Vila "and the ceftazidime-avibactam combination may represent an excellent alternative to treat infections caused by multi-resistant bacteria".

Fluoroquinolones are broad spectrum antibiotics that were developed in the 60's and work by inhibiting bacterial DNA replication. They are used to treat severe infections, particularly those associated to hospitals. However, due to their excessive misuse, a many bacteria have developed resistance by mechanisms such as efflux pumps that decrease intracellular concentrations of the drug. Therefore, it is of vital importance to find new compounds, such as cefatizidime-avibactam, that are not affected by such mechanisms of resistance. This combination was recently approved by the FDA for the treatment of complicated urinary and intra-abdominal infections caused by antibiotic-resistant bacteria.

Reference

Pitart C, Marco F, Keating TA, Nichols WW, Vila J. Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa. 2015. Antimicrob Agents Chemother. 59(6):3059-65.