Emergence of Imipenem-Resistant Gram-Negative Bacilli in Intestinal Flora of Intensive Care Patients

Abstract

ABSTRACTIntestinal flora contains a reservoir of Gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36Pseudomonas aeruginosastrains, 12Stenotrophomonas maltophiliastrains, 6Enterobacteriaceaestrains, and 2Acinetobacter baumanniistrains. InP. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In theEnterobacteriaceaestrains, resistance was due to AmpC cephalosporinase and/or extended-spectrum β-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 carbapenemase-producingP. aeruginosastrains, 2Klebsiella pneumoniaestrains, and 2S. maltophiliastrains). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.