Risk of emergence of Pseudomonas aeruginosa resistance to β-lactam antibiotics in intensive care units

Objective: The 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. Design: We conducted an open prospective study over a 3-yr period by including all patients in whom A aeruginosa had been isolated from one or more specimens: bronchial aspiration, blood cultures, catheters, and urinary cultures. Setting: General intensive care unit. Patients: One hundred and thirty-two intensive care unit patients. Interventions: The 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 Results. Forty-two strains became resistant, 30 to one antibiotic, nine to two, and three to three, leading to the study of 57 resistant strains. lmipenem (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, 2.930.2) 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. Conclusions: Our 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.