Fortimicin A: collaborative in vitro susceptibility. Comparison with amikacin and gentamicin against 11,840 clinical bacterial isolates

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Fortimicin A, a pseudodisaccharide aminoglycoside, was found to have broadspectrum activity against most clinically important aerobic and facultatively anaerobic bacteria, except Pseudomonas aeruginosa, some other Pseudomonas species, and streptococci. It was comparable to amikacin in its level of activity (miniimum inhibitory concentrations) and spectrum of activity (except for the lack of activity on P. aeruginosa). Fortimicin A was bactericidal and was affected by cations when tested against P. aeruginosa. Minimum inhibitory concentrations were affected by the inoculum used in the susceptibility test. The drug was resistant to most aminoglycoside-inactivating enzymes, but probably is not active against perneability mutants.Fortimicin A is the most active member of the fortimicin complex of aminoglycosidic antibiotics produced by Micromonospora olivoastrospora (6,8). It is a pseudodisaccharide-incorporating fortamine, a novel aminocyclitol (3). It possesses a broad spectrum of activity against gram-positive and gram-negative bacteria, but is less active against Pseudomonas aeruginosa than are some of the other newer aminoglycosides (4-6). It is resistant to the activity of some of the aminoglycoside-inactivating enzymes (4, 9).In this study we compared the antibacterial activity of fortimicin A with those of five other aminoglycosides (amikacin, gentamicin, netilmicin, sisomicin, and tobramycin) by testing them against a group of bacteria selected to represent a wide variety of genera and species with various susceptibility patterns and mechanisms of resistance. We also determined the bactericidal activity and the effect of changes in cation content of the medium and in inocula on the in vitro activity of the drug.MATERLALS AND METHODSProtocol. The primary investigators developed a protocol for the collaborative investigation of the drug in three laboratories (10). The in vitro activity of the drug against the organism was determined in two laboratories, Center for Disease Control, Atlanta, Ga.,and University of California, Davis. Comparable results have been repeatedly obtained in these two laboratories, but to ensure this interlaboratory agreement, some strains of each genus were tested in both laboratories (only one set of data was reported for these strains).The effect of inoculum changes on the minimum inhibitory concentrations (MICs) for some of these strains was determined in a third laboratory (Kaiser Foundation Hospital Laboratories, Portland, Ore.).Antibiotics. Antibiotic powders suitable for antimicrobial susceptibility tests were obtained as follows: fortimicin A from Abbott Laboratories, Chicago, Ill.; gentamicin, sisomicin, and netilmicin from Schering Corp., Bloomfield, N.J.; amikacin from Bristol Laboratories, Syracuse, N.Y.; and tobramycin from Lilly Laboratories, Indianapolis, Ind.Bacteria. This collection of organisms was assembled for the purpose of challenging this aminoglycoside with a wide range of species and of resistance patterns without regard to usual distribution, as described prev...

Section: Materlals and Methodssupporting

confidence: 83%

Section: Materlals and Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Antibacterial activity of fortimicin A compared with those of five other aminoglycosides, and factors affecting susceptibility tests

Thornsberry¹,

Barry²,

Jones³

et al. 1981

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“…Fortimicin A, the most active naturally occuring member of this class, has antimicrobial activity similar to that of amikacin, but lacks significant activity against Pseudomonas aeruginosa (3,7,12).…”

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confidence: 99%

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

Girolami¹,

Stamm²

1980

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.

“…1, compound 1), the major component of the fortimicin complex, has high, broad-spectrum antibacterial activity (2,4). In addition, fortimicin A has remarkable activity against a wide variety of microorganisms resistant to many of the pseudotrisaccharide aminoglycoside antibiotics (4).…”

mentioning

confidence: 99%

Synthesis of 3-O-demethylfortimicins

Martin¹,

Johnson²,

Tadanier³

et al. 1980

Treatment of fortimicin B with lithium in ethylamine gave 3-O-demethylfortimicin B. The latter was converted by methodology developed with fortimicin B to 3-O-demethylfortimicin A, 4-N-sarcosyl-3-O-demethylfortimicin B, 4-N-beta-alanyl-3-O-demethylfortimicin B, and 4-N-(beta-aminoethyl)-3-O-demethylfortimicin B. 3-O-demethylfortimicin A and the 4-N-acyl-3-O-demethylfortimicins B had appreciably higher antibacterial activities than the corresponding parent fortimicins. Most significant was the increased activity of 3-O-demethylfortimicin A relative to fortimicin A against a variety of strains of Pseudomonas aeruginosa.