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The minimal inhibitory concentrations of gentamicin and minocycline alone and in combination were determined by a broth microdilution method for 100 aerobic, facultative, and anaerobic isolates representative of pathogens recovered from patients with intra-abdominal sepsis. Gentamicin inhibited all strains of Klebsiella, Enterobacter, and Pseudomonas aeruginosa in concentrations of 0.4 to 3.1 mug/ml and all strains of Escherichia coli and Proteus mirabilis in concentrations of 0.8 to 12.5 mug/ml. Whereas minocycline did not consistently inhibit these organisms in concentrations of 1.6 mug or less/ml, it did act synergistically with gentamicin against 43% of the Enterobacteriaceae tested in clinically achievable concentrations; significant synergy was most common with E. coli (60%). Minocycline inhibited 62% of Bacteroides fragilis, 71% of Clostridium, 40% of anaerobic cocci, and 40% of enterococci tested in concentrations of 1.6 mug or less/ml. Whereas gentamicin rarely inhibited these organisms in concentrations of 6.2 mug or less/ml, it did act synergistically with minocycline against 20% of B. fragilis, 67% of Clostridium, 22% of anaerobic cocci, and 22% of enterococci (which had minimal inhibitory concentrations of minocycline within the range tested) at clinically achievable concentrations. Although only four (13%) of the 30 isolates resistant to both gentamicin and minocycline alone were inhibited by clinically achievable concentrations of the combination, the observed synergy, particularly against strains of E. coli, was considered to be of potential clinical usefulness. Antagonism between gentamicin and minocycline was not observed at the concentrations tested.

In Vitro Activity of Gentamicin and Minocycline Alone and in Combination Against Bacteria Associated with Intra-Abdominal Sepsis