Activity of cefotaxime/desacetylcefotaxime with two aminoglycosides against gram-negative pathogens: an example of interactive synergy.

The susceptibility patterns of clinical Gram-negative isolates were determined to cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination with gentamicin (GENT) or tobramycin (TOB) by an agar dilution technique. A constant ratio of 1:1 (CTX to dCTX) was tested throughout the study. Isolates were challenged with subinhibitory levels of TOB or GENT in combination with clinically achievable levels of CTX, dCTX and CTX/dCTX to examine the interactions of the agents. Results of this study demonstrate that CTX/dCTX interacts synergistically with aminoglycosides against many Gram-negative pathogens. Synergy (defined as a fourfold or greater decrease in minimum inhibitory concentration (MIC) when CTX/dCTX was compared to CTX/dCTX/TOB) was demonstrable for 55% of isolates tested. Similarly, 45% were synergistically inhibited by CTX/dCTX/GENT. Additivism (a 2-fold decrease in MIC with the same comparisons) was evident for an additional 18 isolates for CTX/dCTX/TOB and 19 with CTX/dCTX/GENT. When data for Pseudomonas spp. were excluded from the analysis, synergy or additivism was evident with CTX/dCTX/TOB for 88% of the organisms tested and 72% with CTX/dCTX/GENT. Synergistic synergy for CTX/dCTX/TOB (an 8- to greater than 16-fold decrease in MIC for CTX) was demonstrable for 35 and 32 of 82 nonspeudomonal isolates respectively with the TOB and GENT combinations. Ninety nine percent of the nonspeudomonal isolates were inhibited by less than 4 micrograms/ml of CTX, 4 micrograms/ml of dCTX and 0.12 micrograms/ml of TOB, or 0.25 micrograms/ml of GENT, respectively.