Comparative in vitro activities of meropenem, imipenem, temocillin, piperacillin, and ceftazidime in combination with tobramycin, rifampin, or ciprofloxacin against Burkholderia cepacia isolates from patients with cystic fibrosis

We evaluated the activities of meropenem, imipenem, temocillin, piperacilli n, and ceftazidime by determination of the MICs for 66 genotypically charac terized Burkholderia cepacia isolates obtained from the sputum of cystic fi brosis patients. In vitro synergy assays, as performed by the time-kill met hodology, of two- and three-drug combinations of the beta-lactams with tobr amycin, rifampin, and/or ciprofloxacin were also performed with 10 strains susceptible, intermediate, or resistant to fluoroquinolones. On the basis o f the MICs, meropenem and temocillin were the most active beta-lactam agent s,,vith MICs at which 90% of isolates are inhibited of 8 and 32 mu g/ml, re spectively, The addition of ciprofloxacin significantly enhanced the killin g activities of piperacillin, imipenem, and meropenem against the 10 strain s tested (P < 0.05), The best killing activity was obtained with the combin ation of meropenem and ciprofloxacin, with bactericidal activity of 3.31 +/ - 0.36 log(10) CFU/ml (P < 0.05). Compared to the activity of the two drug beta-lactam-ciprofloxacin combination, the addition of rifampin or tobramyc in did not significantly increase the killing activity (P > 0.05). The thre e-drug combinations (with or without ciprofloxacin) significantly enhanced the killing activities of piperacillin, imipenem, and meropenem relative to the activities of the beta-lactams used alone (P < 0.05). The combination beta-lactam-ciprofloxacin-tobramycin was the combination with the most cons istently synergistic effect.