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Journal of Antimicrobial Chemotherapy (1996) 38, 809-818
© 1996 The British Society for Antimicrobial Chemotherapy

other

Aerosolization of imipenem/cilastatin prevents pseudomonas-induced acute lung injury

S. Hashimotoa, E. Wolfeb, B. Guglielmob, R. Shanksa, J. Sundelofd, J. F. Pittetc, E. Thomasc and J. Wiener-Kronishc,*

aDepartment of Anesthesiology and Intensive Care Medicine, Kyoto Prefectural University of Medicine Kyoto Japan 602 bDivision of Clinical Pharmacy, University of California at San Francisco CA cDepartment of Anesthesia and Medicine, University of California at San Francisco CA dMerck Research Lab Rahway, NJ, USA

Received 19 February 1996; returned 27 March 1996; accepted 29 May 1996

*Correspondence to: Jeanine Wiener-Kronish, MD, Box 0624, Department of Anesthesia and Critical Care, University of California, San Francisco, CA 94143; USA. Tel: +1 415-476-1116

Aerosolization of imipenem/cilastatin was compared with continuous intravenous infusions of the antibiotic for pharrnacokinetic/pharmacodynarnic analysis. The concentrations of imipenim/cilastatin in bronchoalveolar lavage fluids (BAL) obtained from rats exposed to the aerosolized antibiotic were significantly greater than the concentrations in BAL in the rats that had received intravenous infusions of imipenem/cilastatin. The two methods of antibiotic delivery were compared for their effects on bacterial-induced lung injury in rats that had Pseudomonas aeruginosa instilled into their airspaces. The aerosolization of antibiotic was associated with significantly decreased bacterial-induced lung injury. The high concentrations of antibiotic in the airspaces secondary to aerosolization appears to kill bacteria more quickly and preserve lung epithelial and endothelial integrity better than systemic delivery of the same antibiotic.


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