Nebramycin

Abstract: Tobramycin (factor 6 of the nebramycin complex) is a new aminoglycoside antibiotic isolated from Streptomyces tenebrarius which is active against S. aureus, Enterobacteriaceae, and Pseudomonas aeruginosa. Susceptibility to tobramycin of 96 strains of P. aeruginosa, including 45 recent isolates from blood, was studied by using agar and broth dilution methods. The minimum inhibitory concentration (MIC) for 83 of 96 strains was 3.12 μg/ml or lower in Mueller Hinton agar; MIC values were two to eight times lower in Mueller Hinton broth tests. Agar dilution MIC values were generally lower than those obtained in parallel tests with gentamicin. Killing curves obtained from serial sampling of broth cultures showed a 100- to 10,000-fold decline in viability of log-phase organisms within 30 min of exposure to the drug. Two-dimensional agar dilution tests with carbenicillin and tobramycin with 79 strains showed additive or synergistic effects; no antagonism was documented. Seventy-eight of 79 strains were inhibited by a combination of 50 μg of carbenicillin per ml and 1.56 μg of tobramycin per ml, blood levels which seem attainable in man. Tobramycin appears to be a potent, rapidly bactericidal antibiotic against P. aeruginosa and merits clinical evaluation.

Abstract: Resistance to the aminoglycoside gentamicin in the nebramycin producer, Streptomyces tenebrarius, occurs at the level of the ribosome. A resistance determinant isolated from this actinomycete was previously shown to encode a methylase enzyme which modifies residue G-1405 of 16S ribosomal RNA. This gene (kgmB) has been sequenced and expressed in Escherichia coli using lacZ transcriptional signals since, like many other actinomycete genes, kgmB is not expressed in E. coli from its own promoter. The 5′ end of the kgmB transcript has been mapped revealing a single promoter which does not obviously conform to the prokaryotic consensus.