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. 2022 Oct 3;26(1):300.
doi: 10.1186/s13054-022-04164-0.

Oropharyngeal and intestinal concentrations of opportunistic pathogens are independently associated with death of SARS-CoV-2 critically ill adults

Juliette Patrier  1 , Khanh Villageois-Tran  2   3 , Piotr Szychowiak  1   3 , Stéphane Ruckly  3   4 , Rémi Gschwind  3 , Paul-Henri Wicky  1 , Signara Gueye  5 , Laurence Armand-Lefevre  3   5 , Mehdi Marzouk  1 , Romain Sonneville  1   3   4 , Lila Bouadma  1   3   4 , Marie Petitjean  3 , Fariza Lamara  1   4 , Etienne de Montmollin  1   3   4 , Jean-Francois Timsit  6   7   8 , Etienne Ruppé  3   5 ; French COVID Cohort Study Group
Collaborators, Affiliations

Oropharyngeal and intestinal concentrations of opportunistic pathogens are independently associated with death of SARS-CoV-2 critically ill adults

Juliette Patrier et al. Crit Care. .

Abstract

Background: The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to the intensive care unit (ICU). The dominance by opportunistic pathogens (such as Enterococcus) has been associated with death. However, whether this association remains all throughout the hospitalization are lacking.

Methods: We performed a single-center observational prospective cohort study in critically ill patients admitted with severe SARS-CoV-2 infection. Oropharyngeal and rectal swabs were collected at admission and then twice weekly until discharge or death. Quantitative cultures for opportunistic pathogens were performed on oropharyngeal and rectal swabs. The composition of the intestinal microbiota was assessed by 16S rDNA sequencing. Oropharyngeal and intestinal concentrations of opportunistic pathogens, intestinal richness and diversity were entered into a multivariable Cox model as time-dependent covariates. The primary outcome was death at day 90.

Results: From March to September 2020, 95 patients (765 samples) were included. The Simplified Acute Physiology Score 2 (SAPS 2) at admission was 33 [24; 50] and a Sequential Organ Failure Assessment score (SOFA score) at 6 [4; 8]. Day 90 all-cause mortality was 44.2% (42/95). We observed that the oropharyngeal and rectal concentrations of Enterococcus spp., Staphylococcus aureus and Candida spp. were associated with a higher risk of death. This association remained significant after adjustment for prognostic covariates (age, chronic disease, daily antimicrobial agent use and daily SOFA score). A one-log increase in Enterococcus spp., S. aureus and Candida spp. in oropharyngeal or rectal swabs was associated with a 17% or greater increase in the risk of death.

Conclusion: We found that elevated oropharyngeal/intestinal Enterococcus spp. S. aureus and Candida spp. concentrations, assessed by culture, are associated with mortality, independent of age, organ failure, and antibiotic therapy, opening prospects for simple and inexpensive microbiota-based markers for the prognosis of critically ill SARS-CoV-2 patients.

Keywords: Biomarker; COVID-19; Candida; Enterococcus; Microbiota; Resuscitation; Staphylococcus aureus.

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Conflict of interest statement

ER received research grants from bioMérieux, consulting fees from Illumina and speaker fees from Eumedica. Unrelated to the research presented: JFT participated to advisory board for Pfizer, Gilead, Merck, Medimune, BD, Paratek. JFT received fees for lectures for Gilead, Pfizer, Merck, BD. JFT received research grants from Thermofischer, Merck, Pfizer. The other authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Boxplot representation of the oropharyngeal (blue) and rectal (red) concentrations of Enterococcus spp. according to the sampling time range. Bars indicate the percentage of positive sample and number in red indicates median (IQR) values of positive samples
Fig. 2
Fig. 2
Boxplot representation of the oropharyngeal (blue) and rectal (red) concentrations of S. aureus according to the sampling time range. Bars indicate the percentage of positive sample and number in red indicates median (IQR) values of positive samples
Fig. 3
Fig. 3
Boxplot representation of the oropharyngeal (blue) and rectal (red) concentrations of Candida sp. according to the sampling time range. Bars indicate the percentage of positive sample and number in red indicates median (IQR) values of positive samples
See this image and copyright information in PMC

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