Tiacumicins, a novel complex of 18-membered macrolide antibiotics. I. Taxonomy, fermentation and antibacterial activity.

A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41. The producing culture, isolated from a soil sample collected in Hamden, Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D. aurantiacum subsp. hamdenesis subsp. nov. The antibiotic complex was produced in a New Brunswick 150-liter fermentor using a medium consisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts. Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.

Antimicrobial activity of cefmenoxime (SCE-1365).

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and cefamandole against a broad spectrum of 486 organisms and with that of cefotaxime against 114 organisms. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against those organisms tested and were the most active of these cephalosporins against all aerobic and facultative organisms except Staphylococcus aureus. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90% of strains tested (MIC(90)) ranged from 0.06 to 8 mug/ml for the Enterobacteriaceae. The MIC(90)s for gram-positive cocci were 0.015 and 128 mug/ml with good activity against the gram-positive organisms. In addition, cefmenoxime activity was bactericidal and only slightly affected by differences in inoculum size. The combination of cefmenoxime and gentamicin was synergistic against 80% of the Enterobacteriaceae and 100% of P. aeruginosa strains tested. Development of resistance to cefmenoxime was slow or absent for organisms with low initial MICs but more rapid for those with higher initial MICs. Cefmenoxime exhibited good protective activity in mice infected with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, or S. aureus but was less effective against P. aeruginosa.

Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A.

The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staphylococcus aureus, with ODMF most active against Proteus mirabilis, indole-positive Proteus, and Providencia and gentamicin most active against other species. Activity of each of the antibiotics against group D streptococci was poor. The overall activity of ODMF was superior to that of fortimicin A for all groups of organisms examined and was most pronounced, approximately three-fold, against strains of Pseudomonas aeruginosa. Both ODMF and fortimicin A were resistant to the action of several aminoglycoside-inactivating enzymes, with the exception of 3-N-acetyltransferase-I. ODMF and fortimicin A showed similar rapid bactericidal effects at multiples of the minimum inhibitory concentration and equivalent synergistic activity against enterococci when combined with penicillin G. The combination of carbenicillin with ODMF, fortimicin A, or gentamicin was synergistic for approximately 80% of the P. aeruginosa strains tested. Inactivation of ODMF and fortimicin A when combined with carbenicillin in vitro was minimal or absent, whereas gentamicin was substantially inactivated under similar conditions. ODMF, fortimicin A, and gentamicin exhibited protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, S. aureus, or P. aeruginosa. Gentamicin was the most active, followed by ODMF and fortimicin A. The superior in vitro activity of ODMF compared with fortimicin A against P. aeruginosa was confirmed in vivo.

Fortimicins A and B, new aminoglycoside antibiotics. IV. In vitro study of fortimicin A compared with other aminoglycosides.

The in vitro antimicrobial activity of fortimicin A, the most active member of the fortimicin complex, was compared with that of amikacin, gentamicin, sagamicin and tobramycin against 352 strains of Enterobacteriaceae and other medically significant organisms. Against most of these organisms fortimicin and amikacin had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin, sagamicin or tobramycin. Fortimicin had relatively weak activity against Pseudomonas aeruginosa strains. Fortimicin shows many of the characteristics of other aminoglycoside antibiotics: (i) improved activity at alkaline pH, (ii) rapid, bactericidal action, (iii) reduced activity with increasing inoculum levels, and (iv) synergistic activity with penicillin against enterococci. The activity of fortimicin was compared to that of gentamicin, tobramycin and amikacin against a group of 95 naturally occurring, antibiotic-resistant Gram-negative bacilli other than Pseudomonas. The organisms were isolated from clinical sources and selected primarily for gentamicin resistance by the sensitivity disc test. Fortimicin showed excellent activity against this group of organisms. At a concentration of 6.2 mcg/ml, fortimicin inhibited the most strains (92.6%) followed by amikacin (90.5%), gentamicin (23.2%) and tobramycin (8.4%).

Inhibitory effect of light on growth-supporting properties of eosin methylene blue agar.

Exposure of eosin methylene blue agar to visible light can alter the ability of that medium to support microbial growth. Proteus species were most sensitive to the photodynamic action.