Use of a new mouse model of Acinetobacter baumannii pneumonia to evaluate the postantibiotic effect of imipenem

被引:88
作者
JolyGuillou, MC
Wolff, M
Pocidalo, JJ
Walker, F
Carbon, C
机构
[1] HOP BICHAT CLAUDE BERNARD, CLIN REANIMAT MALAD INFECT, F-75018 PARIS, FRANCE
[2] HOP BICHAT CLAUDE BERNARD, INSERM U13, F-75018 PARIS, FRANCE
[3] HOP BICHAT CLAUDE BERNARD, ANAT PATHOL LAB, F-75018 PARIS, FRANCE
关键词
D O I
10.1128/AAC.41.2.345
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Acinetobacter baumannii is responsible for severe nosocomial pneumonia, To evaluate new therapeutic regimens for infections due to multiresistant strains and to study the pharmacodynamic properties of various antibiotics, we developed an experimental mouse model of acute A. baumannii pneumonia, C3H/HeN mice rendered transiently neutropenic were infected intratracheally with 5 x 10(6) CFU of A. baumannii. The mean log(10) CFU/g of lung homogenate (+/- the standard deviation) were 9 +/- 0.9, 9.4 +/- 0.8, 8.6 +/- 1.2, and 7.7 +/- 1.4 on days 1, 2, 3, and 1 postinoculation, The lung pathology was characterized by pneumonitis with edema and a patchy distribution of hemorrhages in the peribronchovascular spaces of both lungs, Abscesses formed on days 3 and 4. Four days after inoculation, subacute pneumonitis characterized by alveolar macrophage proliferation and areas of fibrosis was observed. The cumulative mortality on day 4 was 85%. This new model was used to study the effects of 1, 2, or 3 50-mg/kg doses of imipenem, Imipenem concentrations in lungs were above the MIC for 2 h after the last dose, The in vivo postantibiotic effect (PAE) was determined during the 9-h period following the last dose; it decreased in duration with the number of doses: 9.6, 6.4, and 4 h after 1, 2, and 3 50-mg/kg doses, respectively, In contrast, no in vitro PAP was observed, This model offers a reproducible acute course of A. baumannii pneumonia, The presence of a prolonged in vivo PAE supports the currently recommended dosing intervals of imipenem for the treatment of human infections due to A. baumannii, i.e., 15 mg/kg three times a day.
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页码:345 / 351
页数:7
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