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Updated: Aug 13, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
In vitro antimicrobial spectrum, occurrence of synergy, and recommendations for dilution susceptibility testing
R N Jones1, A L Barry, R R Packer
1Clinical Microbiology Institute, Tualatin, Oregon 97062.
Abstract:
Broth microdilution tests and an antimicrobial interaction (synergy) studies using various combinations of cefoperazone and sulbactam were performed in an effort to determine the most appropriate in vitro dilution test system. The test results with cefoperazone and sulbactam were categorized as synergistic (complete or partial) for nearly 80% of the strains isolated from clinical trial patients. The results indicate that the cefoperazone-sulbactam fixed ratio (2:1) maximized the cefoperazone spectrum of activity and best approximated the parenteral formulation of the drug. The cefoperazone-sulbactam combination had a greater antimicrobial activity than did the other comparison beta-lactams, except for imipenem, tested against strains of the family Enterobacteriaceae. To be consistent with the National Committee for Clinical Laboratory Standards interpretive breakpoints for cefoperazone alone, the following MIC breakpoints should be applied to the combination (2:1 ratio): less than or equal to 16/8 micrograms/ml, susceptible; 32/16 micrograms/ml, moderately susceptible; and greater than or equal to 64/32 micrograms/ml, resistant.
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