Effects of selective digestive decontamination (SDD) on the gut resistome.
OBJECTIVE
Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibiotic-resistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches.


METHODS
We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD.


RESULTS
The patient microbiota was highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2″)-Ib and an aadE-like gene. We show that aph(2″)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ∼10(4) fold increase to a ∼10(-10) fold decrease in relative abundance during SDD.


CONCLUSIONS
ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Elena
E
Buelow
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
Teresita Bello
TB
Gonzalez
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
Dennis
D
Versluis
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Evelien A N
EA
Oostdijk
Center for Biomedical and Health Science Research, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK Department of Vertebrate Genomics, Max Planck Institute for Infection Biology, Berlin, Germany.
Lesley A
LA
Ogilvie
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Maaike S M
MS
van Mourik
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Els
E
Oosterink
Laboratory of Systems and Synthetic Biology, Wageningen University, Wageningen, The Netherlands.
Mark W J
MW
van Passel
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
Hauke
H
Smidt
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Marco Maria
MM
D'Andrea
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Mark
M
de Been
Center for Biomedical and Health Science Research, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK Queen Victoria Hospital NHS Foundation Trust, East Grinstead, UK.
Brian V
BV
Jones
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Rob J L
RJ
Willems
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Marc J M
MJ
Bonten
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands w.vanschaik@umcutrecht.nl.
Willem
W
van Schaik
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D003013:Clostridium / Q000187:drug effects / Q000302:isolation & purification; D003422:Critical Care; D004269:DNA, Bacterial / Q000235:genetics; D003666:Decontamination / Q000379:methods*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005243:Feces / Q000382:microbiology; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008297:Male; D064307:Microbiota / Q000187:drug effects / Q000235:genetics; D008969:Molecular Sequence Data; D009960:Oropharynx / Q000382:microbiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013559:Symbiosis
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D017853:Phosphotransferases (Alcohol Group Acceptor); C048564:aminoglycoside 2''-phosphotransferase
antibiotic resistance; intensive care medicine; metagenomics