Enterobacteriaceae strains having elevated minimal inhibitory concentrations (.2.0 to s32 ,ug/ml) of cefoperazone, cefotaxime, ceftazidime, and moxalactam were synergistically inhibited by amikacin combinations (54.1 to 69.6% occurrence). Indifference was rare (8.1% for moxalactam), and true antagonistic interactions were not observed. Strains resistant or susceptible to these new cephalosporins were also synergistically inhibited by the addition of amikacin, reducing resistant cephalosporin minimal inhibitory concentrations to clinically achievable levels.Amikacin has been recognized as the currently available aminoglycoside most refractory to bacterial enzyme inactivation (18). This stability has generally limited the use of amikacin to those clinical bacterial strains resistant to kanamycin, gentamicin, and tobramycin by enzyme plasmid-mediated mechanisms. Similarly, the recently introduced third-generation cephalosporins have substantial stability to bacterial plactamases and a potent antimicrobial activity (2, 3, 6-9, 15, 16). The bacteria most likely to harbor the higher minimal inhibitory concentrations (MICs) for these new ,B-lactams are the nonfermentative bacilli and the serogroup D Streptococcus spp.; however, a few strains of Enterobacteriaceae may have MICs of 2.0 to 32 ,ug/ml (3,(7)(8)(9). These latter organisms represent a very different population of enteric bacilli only moderately susceptible (MS) to these highly active new drugs. Very few Enterobacteriaceae are currently considered resistant (MICs, .64 ,g/ml) to cefoperazone,' cefotaxime, ceftazidime, or moxalactam.To determine the possibility of using antimicrobial combinations to treat infections caused by these MS strains of Enterobacteriaceae (cefoperazone, cefotaxime, ceftazidime, or moxalactam MICs, 2.0 to 32 ,ug/ml), we screened over 6,000 organisms to find strains having elevated MICs as described above. These recent clinical isolates from The Cleveland Clinic Foundation (Cleveland, Ohio), St. Francis Hospital (Wichita, Kans.), St. Vincent Hospital and Medical Center (Portland, Oreg.), and Northwestern Memorial Hospital (Chicago, Ill.) were collected and then retested for their susceptibility to the new ,-lactams singly and in combination with amikacin. Synergy analysis was determined by the checkerboard broth dilution technique, confirmed by a limited number of bactericidal concentration isobolograms and kill curves. Some additional organisms were tested, including several with resistance to one or more of the five broad-spectrum drugs to detect their possible conversion from resistantto-susceptible MIC results by the addition of another antimicrobial agent.MATERALS AND METHODS Antibiotics. The broad-spectrum drugs utilized in all phases of this study were supplied by the following manufacturers: amikacin, Bristol Laboratories, Syracuse, N.Y.; cefoperazone, Pfizer Inc., New York, N.Y.; cefotaxime, Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.; ceftazidime, Glaxo Inc., Research Triangle Park, N.C.; moxalactam, Eli Lilly & Co., ...