In vitro activity of carumonam (Ro 17-2301; AMA-1080) versus enteropathogenic and nonfermentative gram-negative rods and Legionella pneumophila

Abstract

The in vitro activity of carumonam (Ro 17-2301; AMA-1080) was tested against 355 single-patient isolates, by and large enteropathogenic or nonfermentative rods. The new monobactam was inhibitory and bactericidal against the majority of diarrhea-causing members of the family Enterobacteriaceae at concentrations of less than and equal to 8 ,ug/ml. Although known to be active against Pseudomonas aeruginosa, it generally did not exhibit clinically useful activity against other nonfermenters or against Legionella pneumophila, thus confirming its narrow spectrum of activity.Carumonam (Ro 17-2301; AMA-1080) is a parenterally administered monocyclic beta-lactam (monobactam) currently under clinical development. This new agent has been shown to be active in vitro against many, predominantly gram-negative, aerobic rods, primarily members of the families Enterobacteriaceae and Neisseriaceae, Haemophilus spp., and Pseudomonas aeruginosa (1, 5, 7). Because the activity of carumonam has not been unequivocally defined with regard to its use for enteric and for nosocomial infections, the purpose of the present study was to determine its in vitro activity against the most ubiquitous causative agents of acute bacterial diarrhea, against the main nonfermentative gram-negative rods (except P. aeruginosa), and against Legionella pneumophila.A total of 355 clinical isolates from the culture collection of the Department of Medical Microbiology at the University of Zurich were selected for the study. The MIC of carumonam was determined by the microbroth dilution technique following widely accepted recommendations (8) in wells with 0.1-ml final volume by using cation-unsupplemented Mueller-Hinton broth (Difco Laboratories). The MIC was read with the unaided eye and taken as the lowest concentration of antibacterial agent that suppressed visible bacterial growth. Faintly turbid wells were disregarded. Halophilic Vibrio spp. were tested in Mueller-Hinton broth supplemented with 6.5% NaCl. Susceptibility testing of Campylobacter jejuni was carried out by agar dilution under microaerophilic conditions by using Mueller-Hinton agar (final amount, 2.5% agar) enriched with 7% horse blood incubated in an anaerobic jar without catalyst at 35°C for 48 h (12).Determination of Legionella pneumophila susceptibility (MIC only) was carried out on enriched charcoal-yeast extract agar in room air with added 10% CO2 (2) and 0.5 (1) jig/ml. Data for other organisms were as follows: Yersinia spp., 1 (8) ,ug/ml; Vibrio spp., 16 (16) jig/ml; and Salmonella spp., 1 (>128) j±g/ml. For Campylobacterjejuni, which was still more resistant to the compound, the M'C50 (MIC90) was 8 (128) jig/ml.Results with 191 nonfermentative rods (27 species) are not tabulated, since these bacteria were quite resistatit to caru-