Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Colonization resistance; Critical care; Microbiome; Mortality; Nosocomial infection; Vancomycin-resistant Enterococcus.

Fig. 1.. Rectal carriage of specific bacteria at ICU admission was associated with subsequent infections with the same bacteria.

Rectal carriage status for each organism was classified as present versus absent at ICU admission based on selective culture for vancomycin-resistant Enterococcus (VRE) and 16S sequencing for all other organisms. Domination by Enterococcus was classified categorically based on a cut-off of ≥30% 16S reads as per Taur et. al. Patients were then followed for culture-proven infections with these same organisms. These six organisms represent the most common culture-proven infections within the cohort. In the top part of the figure, blue bars = yes/present and green bars = no/absent. In the bottom part of the figure, the same relationships are shown after adjusting for colonization with VRE, SAPS3 score, the presence of sepsis, heart failure, elevated heart rate, and low serum albumin levels (see Table 1 for co-variable definitions). Blue indicates statistical significance whereas green does not.

Fig. 2.. Patients who were discordant for Enterococcus domination and VRE had increased risk for death or infection regardless of which test was positive.

Enterococcus domination (≥30% reads) was assessed by 16S sequencing while VRE status was assessed using culture on selective media. All patients were followed for 30 days for survival or all-cause culture-proven infections. In general, results for Enterococcus domination and VRE in culture were highly concordant. Log-rank test for equality of the survivor functions across the 4 groups. ICU: intensive care unit; VRE: vancomycin-resistant Enterococcus.