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

Abstract

Objectives: To study the in vitro interaction of gatifloxacin in combination with gentamicin and with the β-lactams cefepime, meropenem and piperacillin against clinical isolates of Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, extended-spectrum β-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. Chequerboard 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 β-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.