In vitro activities of Ro 40-6890 against 164 predominantly intestinal members of the families Enterobacteriaceae and Vibrionaceae

Abstract

The in vitro activities of Ro Ro 40-6890 is the active moiety of a novel cephalosporin ester, Ro 41-3399 (7). It is inhibitory against a broad spectrum of aerobic gram-positive and gram-negative organisms (1). In the present study, we tested its in vitro potencies against predominantly intestinal bacteria of the families Enterobacteriaceae and Vibrionaceae (Vibrio spp.,Aeromonas spp., and Plesiomonas shigelloides). Test strains were single-patient isolates. They were identified by published methods (2) but were not bio-or serogrouped to strengthen their respective pathogenic links to enteropathogenicity (2, 14). We included cefotaxime, cefadroxil, and the amoxicillin-clavulanic acid combination in our testing.A total of 164 clinical isolates (at least 16 species; Salmonella spp. were counted as only one species pending redefinition of the concept of species within the genus) from the culture collection of the Department of Medical Microbiology at the University of Zurich were chosen for the study.The MICs of Ro 40-6890 and the comparative drugs were evaluated by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards (10) with non-cation-adjusted Mueller-Hinton agar. The MICs were read with the naked eye and defined as the lowest concentration of antibacterial agent that inhibited clearly discernible bacterial growth. The growth of five or fewer colonies per plate was disregarded.Ro 40-6890 laboratory powder (lot no. 6069128; potency, 917 jig/mg; courtesy of C. Hubschwerlen) was synthesized at F. Hoffmann-La Roche Ltd., Basel, Switzerland, adjusted for potency deviation, and constituted in sterile water. Cefotaxime, cefadroxil, and amoxicillin were obtained from commercial sources; clavulanic acid was a gift from SmithKline Beecham, Beckenworth, United Kingdom. For the evaluation of the combination amoxicillin-clavulanic acid, a fixed concentration of 2 ,ug of clavulanic acid per ml was used in conjunction with twofold serial dilutions of amoxi-* Corresponding author. The results of our trial demonstrated that the predominantly intestinal members of the families Enterobacteriaceae and Vibrionaceae (Vibno spp., Aeromonas spp., and P. shigelloides) were uniformly very susceptible to (MIC range, c0.03 to 2 p,g/ml; MIC for 50% of isolates [MIC501, 0.06 p,g/ml; MIC90, 0.12 ,g/ml) and cefotaxime, a widely prescribed parenteral aminothiazolyl cephalosporin (MIC range, cO.03 to 2 ,g/ml; MIC50, c0.03 p,g/ml; MIC90, 0.12 p,g/ml) ( Table 1). For 9 of the 16 species, results were superimposable, whereas for the 7 remaining species, the MICs of Ro 40-6890 were 1 to 2 dilution steps lower than those of cefotaxime. The only isolates for which the Ro 40-6890 MIC was 20.25 ,g/ml were limited to the following species (MIC [in micrograms per milliliter], number of isolates): Aeromonas caviae (0.25, 1; 0