Clinical Microbiology and Antimicrobial Chemotherapy. 2015; 17(1):24-32
One of the main mechanisms of resistance of Gramnegative microorganisms to antibiotics is enzymatic hydrolysis by beta-lactamases (for example, metallobeta-lactamases). Searching of paths of strengthening of carbapenems action is possible due to their combined application with the preparations inhibiting the action of metallo-beta-lactamases, irrespective of a genotype of enzymes and their localization (for example, among pharmaceuticals from group of bisphosphonates, allowed for application in clinic). For the first time in our researches it is shown that the combined application of meropenem or imipenem with the preparation «Bonefos» (clodronic acid) strengthens action of the corresponding antibiotic from 4 to 1024 times. This effect is revealed at bisphosphonate in concentration from 1⁄2 MIC to 1⁄64 MIC which appeared up to 68 times less maximal concentration of this preparation in blood serum in 30 minutes after per os single-pass dose. The combined application of carbapenems and bisphosphonates will allow clinical physicians to achieve efficient therapy of the heavy infections caused by Gram-negative high-resistance bacteria producing metal-beta-lactamases.