In-vitro pharmacodynamic studies of piperacillin/tazobactam with gentamicin and ciprofloxacin

Six isolates each of Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Citrobacter spp., Serratia spp., Acinetobacter spp. and Enterobacter spp. (total 60 strains) were studied against the combination of piperacillin/tazobactam plus gentamicin or ciprofloxacin at physiological concentrations by the microtitre chequerboard method incorporating simultaneous time-kill curves. Tazobactam was fixed at 4 mg/L. Gentamicin plus piperacillin/tazobactam was a synergic combination against 28 strains at 2 h, 51 at 5 h and 54 at 24 h as assessed by time-kilt curves and synergic or additive (FBC index less than or equal to 1) against all 60 strains at 24 h by chequerboards. The corresponding figures for ciprofloxacin plus piperacillin/tazobactam were seven, 26, 52 and 58 respectively. Antagonism (FBC index greater than or equal to 4) was demonstrated for one strain to each combination at 24 h. There were no significant differences between FIC indices and FBC indices for each antibiotic combination. Gentamicin plus piperacillin/tazobactam gave greater than or equal to 3 log kill for 47 strains by 2 h, 56 by 5 h and 59 by 24 h. Ciprofloxacin plus piperacillin/tazobactam gave greater than or equal to 3 log kill for 22 strains by 2 h, 36 by 5 h and 56 by 24 h. In conclusion both antibiotic combinations at physiological concentrations were synergic or additive at 24 h for the majority of strains tested although notably gentamicin plus piperacillin/tazobactam gave faster kill. Antagonism was rarely seen. Both combinations are likely to prove beneficial for treatment of serious infections.