• Bernard Georges, Jean-Marie Conil, Anne Dubouix, Maryse Archambaud, Eric Bonnet, Sylvie Saivin, Valérie Lauwers-Cancès, Christelle Cristini, Pierre Cougot, Jean-François Decun, Olivier Mathe, Gérard Chabanon, Nicole Marty, Thierry Seguin, and Georges Houin.
• Anesthésie Réanimation Polyvalente, CHU Rangueil, Toulouse, France.
• Crit. Care Med. 2006 Jun 1;34(6):1636-41.

ObjectiveThe emergence of Pseudomonas aeruginosa resistance to antimicrobial drugs is frequent in intensive care units and may be correlated with the use of some specific drugs. The purpose of our study was to identify a relationship between the use of various beta-lactam antibiotics and the emergence of resistance and to characterize the mechanism of resistance involved.DesignWe conducted an open prospective study over a 3-yr period by including all patients in whom P. aeruginosa had been isolated from one or more specimens: bronchial aspiration, blood cultures, catheters, and urinary cultures.SettingGeneral intensive care unit.PatientsOne hundred and thirty-two intensive care unit patients.InterventionsThe antibiotics studied were amoxiclav, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepim, and imipenem. The mechanisms of resistance studied were production of penicillinase or cephalosporinase, nonenzymatic mechanisms, and loss of porin OprD2. Analysis was performed using Cox proportional-hazard regression with time-dependant variables.Measurements And Main ResultsForty-two strains became resistant, 30 to one antibiotic, nine to two, and three to three, leading to the study of 57 resistant strains. Imipenem (hazard ratio 7.8; 95% confidence interval, 3.4-18.1), piperacillin-tazobactam (hazard ratio 3.9; 95% confidence interval, 1.3-11.9), and cefotaxim (hazard ratio 9.3; 95% confidence interval, 2.9-30.2) were strongly linked to the emergence of resistance. The use of imipenem (p<.0001) was associated with the loss of porin OprD2. Thirty-six strains from nine patients, assayed by pulsed-field gel electrophoresis, showed that for any one patient, all the strains were genetically related.ConclusionsOur results show that there is a high risk of the emergence of drug resistance during treatment with cefotaxime, imipenem, and piperacillin-tazobactam. This has to be taken into account in the therapeutic choice and in the patient's surveillance.

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