Once-daily versus thrice-daily administration of netilmicin in combination therapy ofPseudomonas aeruginosa infection in a man-adapted neutropenic animal model

Abstract

A granulocytopenic mouse model was used to elucidate the impact of dose spacing on the activity of netilmicin against Pseudomonas aeruginosa. A thigh infection was produced and then treated with netilmicin combined with azlocillin. Netilmicin was injected subcutaneously at decreasing doses every 20 min to result in plasma-concentration-time curves similar to those observed in patients on intravenous netilmicin treatment. A once-daily regimen was simulated and compared to a simulated conventional schedule of every 8 h. Identical total amounts of drug were used in both groups of comparatively treated mice. Therapeutic efficacy was quantitated by repeated determinations of surviving organisms in thigh homogenates. Combination therapy was significantly more effective than azlocillin treatment alone. In combination regimens the simulated once-daily netilmicin schedule killed the target organisms faster than the simulated thrice-daily regimen and was significantly more efficacious by 24 and 32 h in two out of three strains of Pseudomonas aeruginosa tested. It is concluded that the results of combination therapy of severe Pseudomonas aeruginosa infections in the immunocompromised host might be improved by choosing an aminoglycoside dosage interval of 24 h instead of the conventional 8 h.

Single or multiple daily doses of aminoglycosides: a meta- analysis

“…However, studies in neutropenic animals have shown a once daily regimen to be of equivalent or superior efficacy,46 47 48 and our meta-analysis showed no loss of efficacy with a single daily dose in neutropenic patients. Our analysis actually suggested that a single dose was superior to multiple doses when the percentage of pseudomonas isolates in a study was higher.…”

Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection

“…However, data from in-vitro and experimental in-vivo studies suggest that once-daily dosing of aminoglycoside might be at least as efficacious and potentially less toxic (Frame et al, 1977;Blaser, Stone & Zinner, 1985a;Gerber et al, 1989;Mattie, Craig & Pechere, 1989). Single-daily dosing of aminoglycosides has also been studied clinically (Powell et al, 1983;Hollender et al, 1989).…”

Therapy with cefoperazone plus sulbactam against disseminated infection due to cefoperazone-resistant Pseudomonas aeruginosa and Escherichia coli in granulocytopenic mice

“…Our animal model is similar to models described by others (4,5). Unlike the previous investigators, we inoculated the microorganisms intraperitoneally to produce disseminated infection.…”