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.2019 Aug 1;69(4):604-613.
doi: 10.1093/cid/ciy936.

Gastrointestinal Microbiota Disruption and Risk of Colonization With Carbapenem-resistant Pseudomonas aeruginosa in Intensive Care Unit Patients

Affiliations

Gastrointestinal Microbiota Disruption and Risk of Colonization With Carbapenem-resistant Pseudomonas aeruginosa in Intensive Care Unit Patients

Melinda M Pettigrew et al. Clin Infect Dis..

Abstract

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonizes the gastrointestinal tract of intensive care unit (ICU) patients, and CRPA colonization puts patients at increased risk of CRPA infection. Prior studies have not examined relationships between the microbiota, medications, and CRPA colonization acquisition.

Methods: Data and perirectal swabs were obtained from a cohort of ICU patients at the University of Maryland Medical Center. Patients (N = 109) were classified into 3 groups by CRPA colonization-acquisition status and antimicrobial exposure. We conducted 16S ribosomal RNA gene sequencing of an ICU admission swab and ≥1 additional swab and evaluated associations between patient characteristics, medications, the gastrointestinal microbiota, and CRPA colonization acquisition.

Results: ICU patients had low levels of diversity and high relative abundances of pathobionts. Piperacillin-tazobactam was prescribed more frequently to patients with CRPA colonization acquisition than those without. Piperacillin-tazobactam was associated with low abundance of potentially protective taxa (eg, Lactobacillus and Clostridiales) and increased risk of Enterococcus domination (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.03-14.92). Opioids were associated with dysbiosis in patients who did not receive antibiotics; potentially protective Blautia and Lactobacillus were higher in patients who did not receive opioids. Several correlated taxa, identified at ICU admission, were associated with lower risk of CRPA colonization acquisition (OR, 0.58; 95% CI, .38-.87).

Conclusions: Antibiotics differed in their impact on the microbiota, with piperacillin-tazobactam being particularly damaging. Certain bacterial taxa (eg, Clostridiales) were negatively associated with CRPA colonization acquisition. These taxa may be markers of risk for CRPA colonization acquisition and/or serve a protective role.

Keywords: antibiotic resistance; antimicrobial stewardship; carbapenem-resistant Pseudomonas; hospital-acquired infection; microbiota.

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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Figures

Figure 1.
Figure 1.
Heatmap of the most abundant gastrointestinal microbiota taxa (n = 66 of 2047 identified) with a proportion >0.001 for ≥90% of 259 perirectal swab samples from 109 intensive care unit patients. The color keys for patient group and swab are indicated on the left. Abbreviation: OTU, operational taxonomic unit.
Figure 2.
Figure 2.
Proportion of samples with domination, defined as ≥30% of reads of a single operational taxonomic unit (OTU), by each of the 5 most frequently identified OTUs by patient and swab. Abbreviation: OTU, operational taxonomic unit.
Figure 3.
Figure 3.
Mean α-diversity indices: Jost1 (effective number of distinct taxa, left panel), Simpson reciprocal index (effective number of abundant taxa, right panel). Abbreviation: SE, standard error.
Figure 4.
Figure 4.
Linear discriminant analysis effect size scores ≥3.0 for comparisons between No. (%) among 109 intensive care unit patients exposed or not exposed to a given antibiotic.A, Vancomycin.B, Piperacillin-tazobactam.C, Antianaerobic antibiotics (ampicillin-sulbactam, cefotetan, clindamycin, imipenem-cilastatin, metronidazole, and piperacillin-tazobactam).D, Antipseudomonal antibiotics (cefepime, ciprofloxacin, gentamicin, imipenem-cilastatin, and piperacillin-tazobactam). Genus names (eg, Anaerococcus) that appear more than once represent different OTUs that are members of the same genus. Abbreviations: abxno, not exposed to antibiotic; abxyes, exposed to antibiotic; LDA, linear discriminant analysis.
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