Activity of BB-K8 (Amikacin) Against Clinical Isolates Resistant to One or More Aminoglycoside Antibiotics

Abstract

One hundred fifty-two bacterial strains that possess resistance to kanamycin A, gentamicin, or tobramycin, or to more than one of these antibiotics, were collected from various sources in Canada, Europe, Japan, and the United States. This collection was composed of Staphylococcus aureus and Pseudomonas aeruginosa and members of the Enterobacteriaceae family. Their susceptibility to BB-K8 (amikacin), a new broad-spectrum semisynthetic derivative of kanamycin A, and to the other agents, was determined on Mueller-Hinton Medium by the twofold agar dilution method. Test results revealed that 60.5% of the isolates were resistant to 8 gg of tobramycin per ml, 67.1% to 8 ,g of gentamicin per ml, 86.2% to 20 ,g of kanamycin A per ml, and only 8.6% to 20 ig of amikacin per ml. Of interest is the fact that the amikacin-resistant strains were generally resistant to all of the other aminoglycosides. The broad spectrum of amikacin was not totally unexpected, because the compound has been shown to be a poor substrate for most enzymes that inactivate other aminoglycosides through O-phosphorylation, O-adenylylation, or N-acetylation. A number of susceptibility profiles were obtained when the organisms were tested against a series of nine aminoglycosides. The majority of these profiles resembled those found for organisms that possess known mechanisms of enzymatic inactivation.

In Vitro Studies with Sch 21420 and Sch 22591: Activity in Comparison with Six Other Aminoglycosides and Synergy with Penicillin Against Enterococci

“…249,1977). Like many new aminoglycosides prepared by chemical modification or mutational biosynthesis (2,3,6), they were designed either to enhance potency of the parent compound and/or resist enzymatic inactivation. The purposes of this study were to (i) evaluate the in vitro activity of Sch 22591 and Sch 21420 against a large number of gram-positive and -negative clinical isolates and (ii) determine whether synergy of these two drugs with penicillin could be demonstrated against enterococci.…”

Antibacterial activities, nephrotoxicity, and ototoxicity of a new aminoglycoside, Win 42122-2

“…At 80 mg/kg, all parameters were normal throughout, except for a significant decrease in osmolality by day 15. At 160 mg/kg, total protein was significantly affected on days 8 and 15, osmolality was significantly affected on days 10 and 15, and volume was significantly affected on day 15.…”

“…The results are shown in Table 8. It can be seen that gentamicin at the 40-mg/kg dose impaired the righting reflex and induced ataxia in all five cats, with the average day of onset occurring on day 17, with the first cat showing evidence of ototoxicity on day 10 Gentamicin-susceptible isolates representing six genera were tested in mouse protection studies in this comparative study and generally showed that the susceptibility patterns observed in vitro were also reflected in vivo. Collectively, the in vitro and in vivo studies revealed that Win 42122-2 had a spectrum similar to that of gentamicin; however, the in vivo activity of gentamicin ranged between 1.4 and 4.1 times more active than Win 42122-2, depending upon the species.…”

Outbreak of Multiply Drug-Resistant Proteus mirabilis Originating in a Surgical Intensive Care Unit: In Vitro Susceptibility Pattern

“…However, organisms resistant to gentamicin have been frequently less susceptible to netilmicin than to amikacin (7,13), as demonstrated in this study. This generally superior activity of amikacin against aminoglycoside-resistant bacteria may be attributable to the isolation of only one enzyme capable of inactivating this drug (17).…”