In vitro activity of newer beta-lactam agents in combination with amikacin against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Serratia marcescens

The in vitro activity of cefoperazone, ceftazidime, ceftizoxime, moxalactam, and N-formimidoyl thienamycin was evaluated alone and in combination with amikacin to assess possible synergistic activity against isolates of amikacin-resistant Pseudomonas aeruginosa and multidrug-resistant Serratia marcescens and Klebsiella pneumoniae susceptible to amikacin (one S. marcescens isolate was also resistant to amikacin). The checkerboard agar dilution method was used. Ceftazidime and thienamycin followed by moxalactam and cefoperazone were the most active agents versus the P. aeruginosa alone and in combination testing. Ceftazidime, moxalactam, and thienamycin showed the greatest activity against S. marcescens, and all agents except cefoperazone were active against K. pneumoniae. The finding of synergy or partial synergy in combination testing was found in the majority with all three genera, including levels below the breakpoint for both amikacin and the beta-lactam agents. This wide in vitro activity indicates that clinical evaluation of these agents in treatment of multidrug-resistant infections is warranted.