Influence of diclofenac sodium on antibiofilm activity of azithromycin

Nowadays bacterial biofilms are the major problem in the medical practice, that can lead to chronic infections and decline of antimicrobial therapy efficacy. Therefore, combined use of drugs of various pharmacotherapeutic groups may offer significant benefits in the research of new ways of treatment infections associated with biofilms. The data of the literature shows that non-steroidal anti-inflammatory drugs have antimicrobial activity and they can be improved antimicrobial action of antibiotics. The aim of the study was to establish specific antibiofilm activity of azithromycin in the combined treatment with diclofenac sodium. Strain S. epidermidis 2265 susceptibility to azithromycin was evaluated by microdilution method and assessed by minimum inhibitory concentration (MIC). Action of azithromycin and diclofenac sodium on biofilm formation and preformed biofilms of S. epidermidis was determined by the crystal violet assay. Our results of study have shown that azithromycin and diclofenac sodium reduced of biofilm formation to abiotic surface. Dose-depending low antibiofilm effect was found under treatment preformed S. epidermidis biofilms with macrolide antibiotic. Diclofenac sodium possessed antibiofilm activity against the preformed 1-day staphylococcal biofilms (reducing biomass 68.5%). Also diclofenac sodium stimulated biofilms formation and increased biomass accumulation of preformed 12-hour and 2-day staphylococcal biofilms to 12.4%. The data obtained of experiments have shown that combined treatment with both azithromycin and diclofenac sodium lead to reduce activity of macrolide against biofilm formation (to 69.5%) and S. epidermidis mature biofilms (2-day) at therapeutic concentrations (increasing biomass accumulation on 10.4% in comparison with controls). Antibiofilm activity of macrolide antibiotic become higher only against preformed 1-day biofilms. The data obtained suggest the possibility of using of azithromycin with diclofenac sodium for treatment of acute purulent-inflammatory processes. Because of diclofenac sodium exhibited antibiofilm activity and increased the antibiotic specific activity, that lead to prevention of development of chronic infections. The issue of combined treatment of azithromycin with diclofenac sodium of chronic infections remains open and requires in-depth research.