title: In vitro activity of gatifloxacin alone and in combination with cefepime, meropenem, piperacillin and gentamicin against multidrug-resistant organisms.
abstract: OBJECTIVE
  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. 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 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.
authors.affiliation: Division of Pediatric Infectious Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA. agnesdawes@pol.net
authors.forename: Maria Agnes
authors.initials: MA
authors.lastname: Dawis
authors.forename: Henry D
authors.initials: HD
authors.lastname: Isenberg
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: France
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Jenkins
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D005839:Gentamicins / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D013845:Thienamycins / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D004338:Drug Combinations; D024841:Fluoroquinolones; D005839:Gentamicins; D010406:Penicillins; D013845:Thienamycins; D000077723:Cefepime; D000077731:Meropenem; D000077734:Gatifloxacin; D010878:Piperacillin