Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin:
Dana C. DresselMichelle A. Tornatore-ReuscherCynthia R. BoschmanValentina StosorTeresa ZembowerMichael PostelnickGary A. NoskinLance R. Peterson
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The effect of ampicillin 25 mg/ml, gentamicin 5 mg/l and methotrexate 10 & 70 mg/l, alone and in combination, was tested for their influence on human polymorphonuclear cell-locomotion, using zymosan or a bacterial filtrate of E. coli, with or without 0.25 and 0.025 mg/l of ampicillin and gentamicin, respectively, as attractants. Methotrexate and gentamicin alone decreased the locomotion, using zymosan as attractant. No effect was observed using the pure bacterial filtrate. The filtrate containing antibiotics displayed a lower ability to induce locomotion when the leucocytes had been pre-treated with antibiotics alone or in combination with methotrexate but not with methotrexate alone. Aspects of these findings are discussed.
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Dactimicin is a new aminoglycoside and its in vitro activity has been compared with that of gentamicin against 100 recent clinical isolates. The minimum inhibitory concentrations were determined by agar dilution. Dactimicin was generally one two-fold dilution step less active or as equally active as gentamicin against enterobacteria and pseudomonas. Dactimicin was several times more active than gentamicin against Acinetobacter and staphylococci. Both compounds share poor activity against enterococci and have a variable effect on other streptococci. They are highly active against serogroup A streptococci and pneumococci.
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Listeria monocytogenes infections are most common in newborn infants and persons with impaired defense mechanisms. There are reports of successful treatment with ampicillin alone: however, there is uncertainty as to what regimen constitutes the most effective therapy. The purpose of this study was to illustrate the in-vitro synergism between ampicillin and gentamicin against L. monocytogenes. Seven strains of L. monocytogenes isolated from bloods or cerebrospinal fluids of infants and three control strains obtained from the Center for Disease Control were tested. Minimal inhibitory concentrations of ampicillin and gentamicin were determined in Todd-Hewitt broth with an inoculum of 10(5) organisms/ml. Killing curves were determined for ampicillin 6 microgram/ml, gentamicin, 0.5 microgram/ml, and the combination of ampicillin, 6 microgram/ml, plus gentamicin, 0.5 microgram/ml. Incubation of approximately 10(7) organisms/ml with these concentrations of ampicillin and gentamicin caused no significant reduction in the viable bacterial population in 24 hours. The combination, on the other hand, was bactericidal in all seven strains isolated from patients and one control strain. The authors believe the ultimate test of the superiority of this combination to ampicillin alone must come from clinical studies. However, the synergistic and bactericidal effects of ampicillin with gentamicin may be very desirable in treatment of newborns and patients with underlying disease.
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Combinations of aminoglycosides plus ampicillin usually are necessary for the satisfactory management of serious Enterococcus faecalis sepsis. A study in a South London hospital demonstrated that 7% of all E. faecalis, and 30% of those from blood cultures, were highly gentamicin resistant. Addition of gentamicin confers no benefit to the treatment of these organisms with ampicillin. We looked at the susceptibility pattern of these organisms in vitro and concluded that ampicillin plus ciprofloxacin offered the best available combination.
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A simple combined agar-strip test (CAST), involving filter paper strips charged with 20 micrograms of ampicillin or 40 micrograms of gentamicin, accurately detected high-level gentamicin resistance among 43 of 146 isolates of Enterococcus faecalis and additive activity of ampicillin plus gentamicin against 101 of 103 (98%) isolates of E. faecalis with moderate-level gentamicin resistance (MLGR). All 15 MLGR Enterococcus faecium isolates were moderately to highly resistant to ampicillin; 5 isolates with moderate resistance to ampicillin (minimal inhibitory concentrations = 16 micrograms/ml) were additively inhibited by ampicillin plus gentamicin, whereas the highly ampicillin-resistant E. faecium isolates yielded an indifferent effect with the CAST procedure.
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