TY - JOUR
T1 - Comparative gut microbiota and resistome profiling of intensive care patients receiving selective digestive tract decontamination and healthy subjects
AU - Buelow, Elena
AU - Bello González, Teresita D J
AU - Fuentes, Susana
AU - de Steenhuijsen Piters, Wouter A A
AU - Lahti, Leo
AU - Bayjanov, Jumamurat R
AU - Majoor, Eline A M
AU - Braat, Johanna C
AU - van Mourik, Maaike S M
AU - Oostdijk, Evelien A N
AU - Willems, Rob J L
AU - Bonten, Marc J M
AU - van Passel, Mark W J
AU - Smidt, Hauke
AU - van Schaik, Willem
N1 - Funding Information:
This work was supported by The Netherlands Organisation for Health Research and Development ZonMw (Priority Medicine Antimicrobial Resistance; grant 205100015) and by the European Union Seventh Framework Programme (FP7-HEALTH-2011-single-stage) “Evolution and Transfer of Antibiotic Resistance” (EvoTAR), under grant agreement number 282004. In addition, W.v.S is supported by a NWO-VIDI grant (917.13.357) and L.L. by Academy of Finland grants 295741 and 307127.
Funding Information:
We thank ServiceXS B.V. (Leiden, The Netherlands) for their assistance in the Fluidigm real-time PCR assays. We are grateful to Erwin Zoetendal and Willem M. de Vos for providing the material and data from the Cohort study of intestinal microbiota among irritable bowel syndrome patients and healthy individuals’ (CO-MIC) funded by the unrestricted Spinoza Award to Willem M. de Vos from The Netherlands Organization for Scientific Research.
PY - 2017/8/14
Y1 - 2017/8/14
N2 - BACKGROUND: The gut microbiota is a reservoir of opportunistic pathogens that can cause life-threatening infections in critically ill patients during their stay in an intensive care unit (ICU). To suppress gut colonization with opportunistic pathogens, a prophylactic antibiotic regimen, termed "selective decontamination of the digestive tract" (SDD), is used in some countries where it improves clinical outcome in ICU patients. Yet, the impact of ICU hospitalization and SDD on the gut microbiota remains largely unknown. Here, we characterize the composition of the gut microbiota and its antimicrobial resistance genes ("the resistome") of ICU patients during SDD and of healthy subjects.RESULTS: From ten patients that were acutely admitted to the ICU, 30 fecal samples were collected during ICU stay. Additionally, feces were collected from five of these patients after transfer to a medium-care ward and cessation of SDD. Feces from ten healthy subjects were collected twice, with a 1-year interval. Gut microbiota and resistome composition were determined using 16S rRNA gene phylogenetic profiling and nanolitre-scale quantitative PCRs. The microbiota of the ICU patients differed from the microbiota of healthy subjects and was characterized by lower microbial diversity, decreased levels of Escherichia coli and of anaerobic Gram-positive, butyrate-producing bacteria of the Clostridium clusters IV and XIVa, and an increased abundance of Bacteroidetes and enterococci. Four resistance genes (aac(6')-Ii, ermC, qacA, tetQ), providing resistance to aminoglycosides, macrolides, disinfectants, and tetracyclines, respectively, were significantly more abundant among ICU patients than in healthy subjects, while a chloramphenicol resistance gene (catA) and a tetracycline resistance gene (tetW) were more abundant in healthy subjects.CONCLUSIONS: The gut microbiota of SDD-treated ICU patients deviated strongly from the gut microbiota of healthy subjects. The negative effects on the resistome were limited to selection for four resistance genes. While it was not possible to disentangle the effects of SDD from confounding variables in the patient cohort, our data suggest that the risks associated with ICU hospitalization and SDD on selection for antibiotic resistance are limited. However, we found evidence indicating that recolonization of the gut by antibiotic-resistant bacteria may occur upon ICU discharge and cessation of SDD.
AB - BACKGROUND: The gut microbiota is a reservoir of opportunistic pathogens that can cause life-threatening infections in critically ill patients during their stay in an intensive care unit (ICU). To suppress gut colonization with opportunistic pathogens, a prophylactic antibiotic regimen, termed "selective decontamination of the digestive tract" (SDD), is used in some countries where it improves clinical outcome in ICU patients. Yet, the impact of ICU hospitalization and SDD on the gut microbiota remains largely unknown. Here, we characterize the composition of the gut microbiota and its antimicrobial resistance genes ("the resistome") of ICU patients during SDD and of healthy subjects.RESULTS: From ten patients that were acutely admitted to the ICU, 30 fecal samples were collected during ICU stay. Additionally, feces were collected from five of these patients after transfer to a medium-care ward and cessation of SDD. Feces from ten healthy subjects were collected twice, with a 1-year interval. Gut microbiota and resistome composition were determined using 16S rRNA gene phylogenetic profiling and nanolitre-scale quantitative PCRs. The microbiota of the ICU patients differed from the microbiota of healthy subjects and was characterized by lower microbial diversity, decreased levels of Escherichia coli and of anaerobic Gram-positive, butyrate-producing bacteria of the Clostridium clusters IV and XIVa, and an increased abundance of Bacteroidetes and enterococci. Four resistance genes (aac(6')-Ii, ermC, qacA, tetQ), providing resistance to aminoglycosides, macrolides, disinfectants, and tetracyclines, respectively, were significantly more abundant among ICU patients than in healthy subjects, while a chloramphenicol resistance gene (catA) and a tetracycline resistance gene (tetW) were more abundant in healthy subjects.CONCLUSIONS: The gut microbiota of SDD-treated ICU patients deviated strongly from the gut microbiota of healthy subjects. The negative effects on the resistome were limited to selection for four resistance genes. While it was not possible to disentangle the effects of SDD from confounding variables in the patient cohort, our data suggest that the risks associated with ICU hospitalization and SDD on selection for antibiotic resistance are limited. However, we found evidence indicating that recolonization of the gut by antibiotic-resistant bacteria may occur upon ICU discharge and cessation of SDD.
KW - Anti-bacterial agents
KW - Antibiotic prophylaxis
KW - Drug resistance
KW - Microbial Intensive care
KW - Microbiome
UR - http://www.scopus.com/inward/record.url?scp=85028386944&partnerID=8YFLogxK
U2 - 10.1186/s40168-017-0309-z
DO - 10.1186/s40168-017-0309-z
M3 - Article
C2 - 28803549
SN - 2049-2618
VL - 5
JO - Microbiome
JF - Microbiome
IS - 1
M1 - 88
ER -