Problems in determination of antibiotic synergism in vitro.

The methods and criteria for testing for synergy were compared by use of 22 strains of Klebsiella pneumoniae and a combination of cephalothin and gentamicin. With the checkerboard technique, the frequency of synergy varied with the criterion employed. When the rate of killing of bacteria by antibiotics was measured, results varied according to the size of inoculum. Comparison of the checkerboard and killing-curve techniques showed poor correlation in terms of the frequency of strains showing synergy. Because clinical observations suggest that treatment of serious infections with combinations of antibiotics that are synergistic in vitro may enhance survival, the methods and criteria for testing for synergy should be standardized.