Activity of Five Aminoglycoside Antibiotics In Vitro Against Gram-Negative Bacilli and Staphylococcus aureus

Abstract

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.

Activity of Three Aminoglycosides and Two Penicillins Against Four Species of Gram-Negative Bacilli

“…This order of activity against the four species of bacteria tested was in agreement with previous reports (22,23). To factor for the differences in pharmacokinetics between amikacin and gentamicin (6), inhibitory indices were calculated to relate potency by weight with achievable serum levels (22). Using this approach, amikacin appears to offer no theoretical advantage over gentamicin, except against isolates of S. marcescens.…”

“…DISCUSSION The spectrum of these aminoglycoside antibiotics was similar but on a weight basis gentamicin was clearly the most active, amikacin intermediate, and aminodeoxybutirosin least active. This order of activity against the four species of bacteria tested was in agreement with previous reports (22,23). To factor for the differences in pharmacokinetics between amikacin and gentamicin (6), inhibitory indices were calculated to relate potency by weight with achievable serum levels (22).…”

“…For gentamicin, this was 4 ug/ml at a dose of 1.5 mg/kg; for amikacin and aminodeoxybutirosin, 16 ,g/ml at a dose of 7.5 mg/kg; and for carbenicillin and BL-P1654, 128 jg/ml for a dose of 4 g and 1 g, respectively. The inhibitory index refers to the ratio between the mean peak serum levels given above and the MIC for at least M of each species tested (22).…”

Peripheral inactivation of gentamicin

“…There seems to be a twofold increase in MIC from pH 7-4-70 (Barber & Waterworth, 1966;Paisley & Washington, 1979). From pH 7'4-65 the increase in MIC may be as low as two-fold for some strains (Sabath & Toftegaard, 1974) fourfold for other strains (Barber & Waterworth, 1966;Sabath & Toftegaard, 1974), or occasionally 8-fold and 16-fold for individual strains (Young & Hewitt, 1973;Strausbaugh & Sande, 1978) (Table). In this context, it should be recalled that pH estimates inside purulent exudates may vary widely from 72-62 (Hays & Mandell, 1974).…”

Sisomicin Versus Netilmicin: In Vitro Susceptibility Testing

“…The similarity of gentamicin and sisomicin has been previously mentioned (2,5,8,9). However, netilmicin has been reported to be significantly more active than gentamicin against clinical isolates of Enterobacteriaceae, Staphylococcus aureus, and Pseudomonas aeruginosa (6).…”