Comparison of methods for assessing in vitro antibiotic synergism against Pseudomonas and Serratia

Infections with Pseudomonas aeruginosa and Serratia marcescens are often difficult to treat because of the narrow therapeutic ratio of available antimicrobials. Synergistic inhibitory and bactericidal activity for gentamicin and carbenicillin against P. aeruginosa has been documented in vitro. The purpose of this study was to compare 4 methods of determining in vitro synergism between several aminoglycosides and penicillins. The agar dilution method using an inoculum replicator was employed, and a drug combination showing inhibition equal to or less than one-fourth of the individual minimal inhibitory concentrations was termed synergistic. Combinations using amikacin and BL-P1654 showed synergism against a greater per cent of strains of P. aeruginosa and S. marcescens than combinations using gentamicin or carbenicillin. Additionally, the "checkerboard" broth dilution method using both minimal inhibitory concentration and minimal bactericidal concentration as endpoints and killing curves according to the methods of Jawetz was studied. Comparison of the results of these 4 methods showed excellent correlation, verifying the consistency of the 4 techniques for determining in vitro synergism.