Comparison of in vitro activity of Sch 21420, a gentamicin B derivative, with those of amikacin, gentamicin, netilmicin, sisomicin, and tobramycin

Abstract

Sch 21420 is a new aminoglycoside synthesized from gentamicin B. Susceptibility tests with Sch 21420, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin were performed on a variety of bacterial species including 44 with known mechanisms of resistance to aminoglycosides. Sch 21420 and amikacin had similar effects on all except Haemophilus influenzae and Neisseria species, which were more susceptible to amikacin. Except with some strains of Serratia marcescens, the drugs used were bactericidal. Sch 21420 and amikacin were more stable than the other four aminoglycosides in the presence of the inactivating enzymes produced by some strains. Strains which were very resistant to Sch 21420 and amikacin either were permeability mutants or produced AAC (6')-I inactivating enzyme. The effect of cations on the susceptibilities of these strains to Sch 21420 and amikacin was seen mostly with Pseudomonas aeruginosa and to Sch 21420 with Acinetobacter. Cations did not affect the susceptibilities of other Pseudomonas species, Enterobacteriaceae, Staphylococcus aureus, or Streptococcus faecalis to Sch 21420 or amikacin.Sch 21420 is an aminoglycoside which was synthesized by a method similar to that used in the synthesis of amikacin, except that gentamicin B was used in place of kanamycin (12). The activity ofthis compound was found to be similar to that of amikacin against the Enterobacteriaceae and Pseudomonas aeruginosa (7,9,11,13,15,17).In this study, we compared the inhibitory and bactericidal activities of Sch 21420 to those of amikacin, gentamicin, netilmicin, sisomicin, and tobramycin against a wide variety of gram-positive and gram-negative organisms. The effect of differences in inoculum size and cation concentration on the activity of these six aminoglycosides was assessed. The activities of these drugs on organisms with various mechanisms of resistance (inactivating enzymes and permeability mutants) were also compared.

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

“…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.,…”

“…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 previously (10 The inocula were prepared from actively growing broth cultures, which were adjusted to match the turbidity of a 0. 5 McFarland standard (7), and were diluted 1:50 in sterile distilled water containing 0.02% Tween 80.…”

“…N. gonorrhoeae isolates were tested by agar dilution as described previously (10,11 Table 1. Fortimicin is active against most of these strains, the exceptions being occasional strains of indole-positive Proteus (including the new genera Morganella morganii and Providencia rettgeri) and Providencia stuartii (1).…”

Resistance to amikacin and isepamicin in rabbits with experimental endocarditis of an aac(6')-Ib-bearing strain of Klebsiella pneumoniae susceptible in vitro

“…In vitro-determined resistance profiles of strains carrying and expressing an aac(6Ј)-Ib gene typically include amikacin and sometimes isepamicin (20,21). Isepamicin, a derivative of gentamicin B, has an activity comparable to that of amikacin against non-AAC(6Ј)-I-producing strains (15,23), but its in vitro activity against strains producing this enzyme has been reported to be somewhat superior to that of amikacin (11).…”

Isepamicin Sulfate-Induced Sensorineural Hearing Loss in Patients with the 1555 A→G Mitochondrial Mutation

“…However, a new type of aminoglycoside antibiotic synthesized from gentamicin, isepamicin sulfate, has recently been developed and introduced in Japan and Europe (Italy and France, as of June, 1997). This antibiotic has the advantage of a broad spectrum of antibacterial activity against both gram-positive and gram-negative bacteria [5][6][7][8] as well as mild side effects [5]. Animal experiments have also shown its reduced nephrotoxicity [9] and ototoxicity [10].…”