IN VITRO SYNERGISTIC EFFECTS OF TAZOBACTAM/PIPERACILLIN WITH VARIOUS ANTIBIOTICS

We investigated in vitro synergistic effects of tazobactam/piperacillin (TAZ/PIPC), a combination drug of tazobactam (TAZ) and piperacillin (PIPC) in the ratio of 1:4, with several other antibiotics against Pseudomonas aeruginosa, Serratia marcescens and methicillin-resistant Staphylococcus aureus (MRSA). Synergistic effects of TAZ/PIPC with each of tobramycin (TOB), netilmicin (NTL), fosfomycin (FOM), ciprofloxacin, minocycline or cefoperazone were observed against all bacteriatested in the checkerboard dilution method. No antagonistic effect was observed in combination of TAZ/PIPC with other antibiotics. Against P. aeruginosa, a combination of TAZ/PIPC with NTL was the most effective, with an average fractional inhibitory concentration (FIC) index of 0.459. And a combination of TAZ/PIPC with FOM was the most the effective against S. marcescens and MRSA. TAZ/PIPC combined with TOB or FOM showed bactericidal effect against P. aeruginosa No.11, S. marcescens No.39 and S. aureus O-62 at concentrations of the drugs that showed only bacteriostatic activity individually. Phase-contrast micrographic observations of P. aeruginosa No.11 and S. marcescensNo.39 demonstrated that the bacterial cells treated with TAZ/PIPC were in filamentous forms and those treated with TOB or FOM were nearly normal. Thecombination of TAZ/PIPC with TOB or FOM induced filamentous cells with spheroplast-like structures and lysis. Those results suggest that the combination of TAZ/PIPC with aminoglycosides or FOM were useful in the treatment of infections by P. aeruginosa, S. marcescens and MRSA, especially those caused by β-lactamase-producing strains.