Effectiveness of netilmicin and tobramycin against Pseudomonas aeruginosa in vitro and in an experimental tissue infection in mice

The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing...

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Published inJournal of antimicrobial chemotherapy Vol. 31; no. 3; p. 403
Main Authors Moffie, B G, Hoogeterp, J J, Lim, T, Douwes-Idema, A E, Mattie, H
Format Journal Article
LanguageEnglish
Published England 01.03.1993
Subjects
Animals
Male
Mice
Microbial Sensitivity Tests
Netilmicin - pharmacokinetics
Netilmicin - pharmacology
Netilmicin - therapeutic use
Pseudomonas aeruginosa - drug effects
Pseudomonas Infections - drug therapy
Tobramycin - pharmacokinetics
Tobramycin - pharmacology
Tobramycin - therapeutic use
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Summary:The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing rate (ER) during 3 h of exposure. On the basis of the quantitative relation between E(R) and the drug concentration, the numbers of cfu expected at consecutive times, at constant as well as at declining concentrations, were predicted. The relationship between observed numbers and predicted values of ERt were similar under both conditions for both drugs. On the same basis the numbers of cfu expected in the experimental thigh infection were predicted. There was indeed a significant linear relationship between observed numbers of cfu in homogenized muscle and the values predicted on the basis of the pharmacokinetics of the aminoglycosides, but the slope of this relationship was only 0.22. There was no difference in this respect between the two antibiotics. It is concluded that the efficacy of netilmicin and tobramycin against P. aeruginosa is considerably less in vivo than in vitro, but the relation is about the same for the two drugs; therefore the slightly higher activity of tobramycin in vitro is relevant in the in-vivo situation.
ISSN:0305-7453
DOI:10.1093/jac/31.3.403