USE OF A NEW MOUSE MODEL OF ACINETOBACTER-BAUMANNII PNEUMONIA TO EVALUATE THE POSTANTIBIOTIC EFFECT OF IMIPENEM

Acinetobacter baumannii is responsible for severe nosocomial pneumonia , To evaluate new therapeutic regimens for infections due to multiresi stant strains and to study the pharmacodynamic properties of various a ntibiotics, we developed an experimental mouse model of acute A. bauma nnii pneumonia, C3H/HeN mice rendered transiently neutropenic were inf ected 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 w ith edema and a patchy distribution of hemorrhages in the peribronchov ascular spaces of both lungs, Abscesses formed on days 3 and 4. Four d ays after inoculation, subacute pneumonitis characterized by alveolar macrophage proliferation and areas of fibrosis was observed. The cumul ative 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 concentrat ions in lungs were above the MIC for 2 h after the last dose, The in v ivo postantibiotic effect (PAE) was determined during the 9-h period f ollowing the last dose; it decreased in duration with the number of do ses: 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 reprod ucible acute course of A. baumannii pneumonia, The presence of a prolo nged in vivo PAE supports the currently recommended dosing intervals o f imipenem for the treatment of human infections due to A. baumannii, i.e., 15 mg/kg three times a day.