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Acquisition of Rectal Colonization by Vancomycin-Resistant Enterococcus among Intensive Care Unit Patients Treated with Piperacillin-Tazobactam versus Those Receiving Cefepime-Containing Antibiotic Regimens

Royal Brisbane and Women's Hospital, University of Queensland, Brisbane, Australia,¹ Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Peennsylvania,² Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio,³ Center for Quality Improvement Research, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio⁴

Received 21 October 2006/ Returned for modification 7 March 2007/ Accepted 6 November 2007

In contrast to expanded-spectrum cephalosporins, beta-lactam-beta-lactamase inhibitor combinations such as piperacillin-tazobactam have rarely been associated with vancomycin-resistant Enterococcus (VRE) colonization and infection. In mice, piperacillin-tazobactam has sufficient antienterococcal activity to inhibit the establishment of colonization during treatment, but this effect has not been confirmed in human patients. We prospectively evaluated the acquisition of rectal colonization by VRE among intensive care unit patients receiving antibiotic regimens containing piperacillin-tazobactam versus those receiving cefepime, an expanded-spectrum cephalosporin with minimal antienterococcal activity. Rectal swabs were obtained weekly and were cultured for VRE. For 146 patients with a negative rectal swab for VRE prior to therapy, there was no significant difference in the frequency of VRE acquisition between patients receiving piperacillin-tazobactam- and cefepime-containing regimens (19/72 [26.4%] and 23/74 [31.1%], respectively; P = 0.28). Of the 19 patients who acquired VRE in association with piperacillin-tazobactam, 10 (53%) developed the new detection of VRE during therapy. Patients initiated on treatment with cefepime-containing regimens were significantly more likely than those initiated on treatment with piperacillin-tazobactam-containing regimens to have received antibiotic therapy in the prior 30 days (55/74 [74.3%] and 22/72 [30.6%], respectively; P < 0.001). These findings suggest that piperacillin-tazobactam- and cefepime-containing antibiotic regimens may be associated with the frequent acquisition of VRE in real-world intensive care unit settings. Although piperacillin-tazobactam inhibits the establishment of VRE colonization in mice when exposure occurs during treatment, our data suggest that this agent may not prevent the acquisition of VRE in patients.

Published ahead of print on 19 November 2007.