The rate ofPseudomonas aeruginosacarbapenem resistance is increasing (2), and one of the major risk factors for carbapenem resistance is carbapenem use (6,7). rates (41%, 25%, and 22%, respectively;P= 0.15) and mortality rates (47%, 25%, and 22%, respectively;P= 0.07). Carbapenem resistance emerged similarly among patients treated with any carbapenem. No carbapenem was superior to another for preventing carbapenem resistance emergence. == INTRODUCTION == Pseudomonas aeruginosa, one of the main microorganisms responsible for ventilator-associated pneumonia (VAP) (1,2), readily acquires antibiotic resistance, and each molecule is usually susceptible to several potential mechanisms of resistance. For example, carbapenem resistance can be due to the production of enzymes, such as AmpC or a metallo–lactamase; overexpression of efflux pumps; porin deficiencies; or target site alterations (35). The rate ofPseudomonas aeruginosacarbapenem resistance is increasing (2), and one of the major risk factors for carbapenem resistance is carbapenem use (6,7). Doripenem is usually a recent antipseudomonal carbapenem that exhibits greaterin vitroactivity againstPseudomonas aeruginosaisolates than other carbapenems and is less likely to select for carbapenem-resistant strains under experimental conditions (811). In one multicenter study, doripenem was shown to be noninferior to imipenem in patients with VAP, and the clinical cure rate was higher with doripenem than imipenem in patients with higher Acute Physiology and Chronic Health Evaluation II scores and older ages (12). However, a recent study found different results and raised doubts about the security of doripenem compared to that Tolnaftate of imipenem in patients withPseudomonas aeruginosaVAP (13). Moreover, most studies that evaluated doripenem activity werein vitrostudies, and uncertainty persists as to the capacity of a given carbapenem to select fewer carbapenem-resistant strains than another. In the Groupe Hospitalier Piti-Salptrire, the three antipseudomonal carbapenems (imipenem, meropenem, Tolnaftate and doripenem) are available and routinely prescribed by physicians in the two intensive care models (ICUs), where a local policy of mixing these three drugs is applied. Therefore, we conducted a prospective, observational study on patients who developedPseudomonas aeruginosaVAP (i) to determine the isolates’ MICs for imipenem, meropenem, and doripenem, (ii) to determine factors and outcomes associated with carbapenem resistance, (iii) to determine factors associated with an unfavorable end TSPAN4 result, defined as death or VAP recurrence, and (iv) and to compare, according to the carbapenem received, the patients’ outcomes and carbapenem resistance emergence for patients with recurrentPseudomonas aeruginosaVAP. == MATERIALS AND METHODS == == Patients. == Consecutive patients that developedPseudomonas aeruginosaVAP in two medicosurgical ICUs in the Groupe Hospitalier Piti-Salptrire teaching hospital were prospectively enrolled. Patients were included when they were 18 years old, were mechanically ventilated, and experienced ventilator-associated pneumonia [defined as the presence of a new or progressive infiltrate(s) on a chest radiograph(s) after at least 48 h of mechanical ventilation (MV) and at least two of the following: (i) fever, defined as a core heat of >38.3C, or hypothermia, defined as a core temperature of <35.0C; (ii) a leukocyte count of 11,000/mm3or 4,500/mm3; or (iii) a new onset of purulent sputum production or respiratory secretions or a change of sputum characteristics (1)] and aPseudomonas aeruginosa-positive culture (either positive quantitative cultures of distal pulmonary secretion samples obtained either by fiberoptic bronchoscopy and bronchoalveolar lavage [BAL; significance threshold, 104CFU/ml] or by guarded mini-BAL [significance threshold, 103CFU/ml] [14] or a positive culture of tracheal secretions obtained by tracheal aspiration [TA; significance threshold, 106CFU/ml]). This epidemiological study was conducted in accordance with the ethical requirements of the Committee for the Protection of Human Research Subjects (CCP le-de-France VI, Groupe Hospitalier Piti-Salptrire, Paris, France). In accordance with French law, no informed consent was obtained because this study did not change existing diagnostic or therapeutic strategies. However, the patients or their relatives received an information sheet describing the study and explaining that they were free to withdraw from it at any time. == Bacteriological procedures. (i) Susceptibility screening. == Pseudomonas aeruginosastrains were isolated from respiratory specimens, and antibiotic susceptibilities were decided using the disk diffusion method. Mueller-Hinton agar and disks of antibiotics were purchased from Sanofi Pasteur Diagnostics (Marne La Coquette, France) and used according to the guidelines of the Antibiogram Committee of the French Society of Microbiology (CA-SFM). Strains responsible for Tolnaftate the first and recurrent episodes were collected, frozen, and stored for future analysis. At the end of.