In vitro activity of gatifloxacin alone and in combination with cefepime, meropenem, piperacillin and gentamicin against multidrug-resistant organisms

Objectives: To study the in vitro interaction of gatifloxacin in combination with gentamicin and with the beta-lactams cefepime, meropenem and piperacillin against clinical isolates of Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae, vancomycin-resistant Enterococcus faecium(VRE) and methicillin-resistant Staphylococcus aureus(MRSA). Methods: The activity of each drug alone was determined by an agar dilution method. Chequer-board synergy testing was then performed against all the isolates. Time-kill assays were done on selected isolates to assess correlation with the chequerboard results. Results: Synergy was demonstrated with the following combinations at achievable serum concentrations: gatifloxacin/piperacillin for 80% and gatifloxacin/cefepime for 60% of S. maltophilia; gatifloxacin/gentamicin for 60%, and gatifloxacin/cefepime for 50% of ESBL-producing K. pneumoniae, and in all drug combinations for 50-70% of P. aeruginosa. Indifference was noted for the majority of B. cepacia and VRE isolates. Antagonism at therapeutic serum levels was observed with gatifloxacin/piperacillin against a single isolate of B. cepacia. No distinct trend in drug interaction was seen with the different drug combinations against MRSA. Time-kill analyses against selected isolates confirmed the synergic activity of the following drug combinations seen in the chequerboard assays: gatifloxacin/cefepime and gatifloxacin/ piperacillin against P. aeruginosa, gatifloxacin/gentamicin against B. cepacia, and gatifloxacin/ gentamicin and gatifloxacin/meropenem against ESBL-producing K. pneumoniae. Conclusions: Gatifloxacin was synergic with the beta-lactams piperacillin, cefepime and meropenem, and with gentamicin against some drug-resistant pathogens. Some of the time-kill analyses against P. aeruginosa, B. cepacia and ESBL-producing K. pneumoniae were in accordance with chequerboard results. Time-kill analyses against S. maltophilia did not confirm the synergy seen in chequerboard testing.