The Anti-Microbial Activity, Beta-Lactamase Stability, and Disk Diffusion Susceptibility Testing of Carumonam (RO 17-2301, AMA-1080), a New Monobactam

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Abstract
Carumonam, a new monobactam, was found to have an antimicrobial spectrum similar to aztreonam. Its spectrum includes Enterobacteriaceae, Haemophilus influenzae, pathogenic Neis⋅: seria species, Pseudomonas aeruginosa, and some streptococci. Staphylococcus species, enterococci, and many other nonenteric gram-negative bacilli were not inhibited. Enterobacteriaceae resistant to cefoperazone (minimum inhibitory concentrations [MICs] ≥32 mg/L) were more likely inhibited by carumonam (52% at ≤8.0 mg/L) than aztreonam (39%) or ceftazidime (35%). Dilution test methods on agar or in Mueller-Hinton broth produced similar results. Carumonam minimum bactericidal concentrations were usually the same or one dilution above the MIC. Carumonam and aztreonam were very stable to most chromosomal (P99, K1, K14) and plasmid-mediated beta-lactamases (TEM, OXA, PSE). The Klebsiella oxytoca enzymes hydrolyzed aztreonam at rates greater than or equal to fivefold higher than carumonam but at a rate less than 1% that of cephaloridine. The aztreonam MICs for these Klebsiella stains were greater than or equal to 32 mg/L, but the hydrolysis rates do not fully explain the high-grade resistance to aztreonam. In vitro susceptibility tests with 30-μg carumonam disks were found to be very predictive. Similar regression statistics were observed for aztreonam and cefotaxime. Recommendations for carumonam susceptibility testing are susceptible greater than or equal to 21 mm (≤8.0 mg/L) and resistant less than or equal to 14 mm (≥32 mg/L). Cross-resistance analysis favors the independent testing of carumonam or aztreonam against gram-negative species other than Enterobacteriaceae and P. aeruginosa.