Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection
- 965 Downloads
Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection.
This was a prospective cohort study of medical ICU adults. Rectal surveillance swabs were performed at admission, selectively cultured for vancomycin-resistant Enterococcus (VRE), and assessed using 16S rRNA gene sequencing. Patients were followed for 30 days for death or culture-proven bacterial infection.
Of 301 patients, 123 (41%) developed culture-proven infections and 76 (25%) died. Fecal biodiversity (Shannon index) did not differ based on death or infection (p = 0.49). The presence of specific pathogens at ICU admission was associated with subsequent infection with the same organism for Escherichia coli, Pseudomonas spp., Klebsiella spp., and Clostridium difficile, and VRE at admission was associated with subsequent Enterococcus infection. In a multivariable model adjusting for severity of illness, VRE colonization and Enterococcus domination (≥ 30% 16S reads) were both associated with death or all-cause infection (aHR 1.46, 95% CI 1.06–2.00 and aHR 1.47, 95% CI 1.00–2.19, respectively); among patients without VRE colonization, Enterococcus domination was associated with excess risk of death or infection (aHR 2.13, 95% CI 1.06–4.29).
Enterococcus status at ICU admission was associated with risk for death or all-cause infection, and rectal carriage of common ICU pathogens predicted specific infections. The gastrointestinal microbiome may have a role in risk stratification and early diagnosis of ICU infections.
KeywordsCritical care Nosocomial infection Vancomycin-resistant Enterococcus Microbiome Colonization resistance Mortality
This research was supported in part by the National Institutes of Health (DK111847) and the American Gastroenterological Association Research Scholar Award (to DEF) and by NIH R01 AI116939 (to ACU).
Compliance with ethical standards
Conflicts of interest
None of the authors have conflicts of interest.
- 2.Garrouste-Orgeas M, Timsit JF, Tafflet M, Misset B, Zahar JR, Soufir L, Lazard T, Jamali S, Mourvillier B, Cohen Y, De Lassence A, Azoulay E, Cheval C, Descorps-Declere A, Adrie C, Costa de Beauregard MA, Carlet J, Group OS (2006) Excess risk of death from intensive care unit-acquired nosocomial bloodstream infections: a reappraisal. Clin Infect Dis 42:1118–1126CrossRefPubMedGoogle Scholar
- 10.Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, No D, Gobourne A, Viale A, Dahi PB, Ponce DM, Barker JN, Giralt S, van den Brink M, Pamer EG (2014) The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124:1174–1182CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Shimizu K, Ogura H, Hamasaki T, Goto M, Tasaki O, Asahara T, Nomoto K, Morotomi M, Matsushima A, Kuwagata Y, Sugimoto H (2011) Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome. Dig Dis Sci 56:1171–1177CrossRefPubMedGoogle Scholar
- 12.Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG (2012) Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 55:905–914CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC (2016) Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315:762–774CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Metnitz PG, Moreno RP, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR, Investigators S (2005) SAPS 3–from evaluation of the patient to evaluation of the intensive care unit. Part 1: objectives, methods and cohort description. Intensive Care Med 31:1336–1344CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Loo VG, Bourgault AM, Poirier L, Lamothe F, Michaud S, Turgeon N, Toye B, Beaudoin A, Frost EH, Gilca R, Brassard P, Dendukuri N, Beliveau C, Oughton M, Brukner I, Dascal A (2011) Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 365:1693–1703CrossRefPubMedGoogle Scholar
- 25.Frencken JF, Wittekamp BHJ, Plantinga NL, Spitoni C, van de Groep K, Cremer OL, Bonten MJM (2018) Associations between enteral colonization with gram-negative bacteria and intensive care unit-acquired infections and colonization of the respiratory tract. Clin Infect Dis 66(4):497–503CrossRefPubMedGoogle Scholar
- 28.Centers for disease control and prevention, methicillin-resistant Staphylococcus aureus infections: ELC prevention collaboratives, accessed on-line at https://www.cdc.gov/HAI/pdfs/toolkits/MRSA_toolkit_white_020910_v2.pdf on 22 Dec 2017
- 34.Byndloss MX, Olsan EE, Rivera-Chavez F, Tiffany CR, Cevallos SA, Lokken KL, Torres TP, Byndloss AJ, Faber F, Gao Y, Litvak Y, Lopez CA, Xu G, Napoli E, Giulivi C, Tsolis RM, Revzin A, Lebrilla CB, Baumler AJ (2017) Microbiota-activated PPAR-gamma signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 357:570–575CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Zaborin A, Smith D, Garfield K, Quensen J, Shakhsheer B, Kade M, Tirrell M, Tiedje J, Gilbert JA, Zaborina O, Alverdy JC (2014) Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness. MBio 5:e01361CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin SK, Emerging Infections Program Healthcare-Associated I, Antimicrobial Use Prevalence Survey T (2014) Multistate point-prevalence survey of health care-associated infections. N Engl J Med 370:1198–1208CrossRefPubMedPubMedCentralGoogle Scholar