Abstract
We performed preclinical and clinical studies of a new monocyclic β-lactam antibiotic carumonam (CRMN, AMA-1080) and obtained the following results:
Antibacterial activity: The antibacterial activity of carumonam on 50 clinical isolates ofPseudomonas aeruginosa and 25 isolates of indole-positiveProteus spp. was compared with that of aztreonam (AZT) and of latamoxef (LMOX). The MIC's of CRMN against the isolates ofP. aeruginosa, when tested with 100-fold diluted inocula, were distributed in the range from 0.78-25 μg/ml, which were similar to those of AZT, but superior by 2-3 steps of concentration to those of LMOX. The MIC's of CRMN against indole-positiveProteus spp. were in the range from≤0. 05-1. 56 μg/ml, similar to those of both AZT and LMOX.
Absorption and excretion: Five healthy male adult volunteers were injected i. v. with 1 g each of CRMN and cefoperazone (CPZ) on a cross-over schedule. Serum concentration of CRMN reached a mean of 118 μg/ml at 5 min, and then decreased with a serum half-life of 1. 21 h. Serum concentration of CPZ reached a mean of 135 μg/ml at 5 min, and then decreased with a serum half-life of 1. 50 h. The 8-h cumulative urinary recovery rate of CRMN was 61. 3%, and that of CPZ only 16. 4%. The results of a study of the renal excretory mechanism of CRMN following probenecid pretreatment suggest that CRMN is excreted through the renal tubules.
Clinical findings: Eight patients with various internal infections were medicated with 2 g daily of CRMN for 3-20 days, and satisfactory clinical response to the treatment was achieved in four. No subjective side-symptoms were recorded in any of the patients. Laboratory studies revealed that S-GOT, S-GPT, ALP and BUN were elevated in one patient each, but no causal relation to the medication was determined.
