<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients

ABSTRACT The Enterobacterales order of Gram-negative bacteria includes the common nosocomial pathogens Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, and Enterobacter species. Intestinal domination by some colonizing bacterial taxa is associated with subsequent infection, but 16S rRNA...

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Autores principales:	Krishna Rao, Anna Seekatz, Christine Bassis, Yuang Sun, Emily Mantlo, Michael A. Bachman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Enterobacterales infection prevention microbiome prognostic indicators Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5a5055bf1b2c4167a34f76cb633f4abd
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spelling	oai:doaj.org-article:5a5055bf1b2c4167a34f76cb633f4abd2021-11-15T15:30:51Z<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients10.1128/mSphere.00450-202379-5042https://doaj.org/article/5a5055bf1b2c4167a34f76cb633f4abd2020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00450-20https://doaj.org/toc/2379-5042ABSTRACT The Enterobacterales order of Gram-negative bacteria includes the common nosocomial pathogens Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, and Enterobacter species. Intestinal domination by some colonizing bacterial taxa is associated with subsequent infection, but 16S rRNA gene sequencing is too costly and slow to be used in a clinical setting. The objectives of this study were to develop a PCR-based assay that can measure Enterobacterales density, validate it against 16S rRNA gene sequencing, and measure the association between Enterobacterales dominance and subsequent infection. Two quantitative PCR (qPCR) assays that were developed to quantify the absolute and relative abundance of Enterobacterales had good correlation with 16S rRNA sequence analysis (P < 0.0001). Using both PCR assays and 16S sequencing, a matched case-control study was performed comparing rectal swabs from hospitalized patients who later developed bloodstream, urinary tract, or respiratory Enterobacterales infections (n = 95) to swabs from patients who remained uninfected (n = 189). Enterobacterales abundance measured by sequencing was high in both cases and controls (means, 31.1% and 27.5%, respectively; P = 0.322). We observed an increased risk of infection that depended on both the absolute and relative abundance of Enterobacterales as measured by qPCR assay A (P = 0.012). After adjustment for albumin levels, central venous catheter presence, and use of cephalosporins at the time of swab collection, this association still approached significance (P = 0.061). These results demonstrate that using qPCR to measure intestinal colonization dominance is feasible, indicate that hospitalized patients have high levels of Enterobacterales colonization, and suggest that both relative and absolute abundance may be associated with subsequent infection. IMPORTANCE Increasing antibiotic resistance has resulted in infections that are life-threatening and difficult to treat. Interventions that prevent these infections, particularly without using antibiotics, could save lives. Intestinal colonization by pathogens, including vancomycin-resistant Enterococcus and carbapenem-resistant Enterobacteriaceae (part of the order Enterobacterales) is associated with subsequent infection, and increased colonization density is associated with increased infection risk. Therefore, colonization offers a window of opportunity for infection prevention if (i) there are rapid and inexpensive assays to detect colonization, (ii) there are safe and effective interventions, and (iii) the risk of infection outweighs the risk of the treatment. Fecal transplants are proof of principle that manipulating the microbiome can reduce such colonization and prevent infections. This study demonstrates the feasibility of implementing rapid and inexpensive assays to quantify colonization and measures the strength of association between Enterobacterales dominance and subsequent infection. The approach described here could be a valuable tool in the prevention of antibiotic-resistant infections.Krishna RaoAnna SeekatzChristine BassisYuang SunEmily MantloMichael A. BachmanAmerican Society for MicrobiologyarticleEnterobacteralesinfection preventionmicrobiomeprognostic indicatorsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterobacterales infection prevention microbiome prognostic indicators Microbiology QR1-502
spellingShingle	Enterobacterales infection prevention microbiome prognostic indicators Microbiology QR1-502 Krishna Rao Anna Seekatz Christine Bassis Yuang Sun Emily Mantlo Michael A. Bachman <italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients
description	ABSTRACT The Enterobacterales order of Gram-negative bacteria includes the common nosocomial pathogens Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, and Enterobacter species. Intestinal domination by some colonizing bacterial taxa is associated with subsequent infection, but 16S rRNA gene sequencing is too costly and slow to be used in a clinical setting. The objectives of this study were to develop a PCR-based assay that can measure Enterobacterales density, validate it against 16S rRNA gene sequencing, and measure the association between Enterobacterales dominance and subsequent infection. Two quantitative PCR (qPCR) assays that were developed to quantify the absolute and relative abundance of Enterobacterales had good correlation with 16S rRNA sequence analysis (P < 0.0001). Using both PCR assays and 16S sequencing, a matched case-control study was performed comparing rectal swabs from hospitalized patients who later developed bloodstream, urinary tract, or respiratory Enterobacterales infections (n = 95) to swabs from patients who remained uninfected (n = 189). Enterobacterales abundance measured by sequencing was high in both cases and controls (means, 31.1% and 27.5%, respectively; P = 0.322). We observed an increased risk of infection that depended on both the absolute and relative abundance of Enterobacterales as measured by qPCR assay A (P = 0.012). After adjustment for albumin levels, central venous catheter presence, and use of cephalosporins at the time of swab collection, this association still approached significance (P = 0.061). These results demonstrate that using qPCR to measure intestinal colonization dominance is feasible, indicate that hospitalized patients have high levels of Enterobacterales colonization, and suggest that both relative and absolute abundance may be associated with subsequent infection. IMPORTANCE Increasing antibiotic resistance has resulted in infections that are life-threatening and difficult to treat. Interventions that prevent these infections, particularly without using antibiotics, could save lives. Intestinal colonization by pathogens, including vancomycin-resistant Enterococcus and carbapenem-resistant Enterobacteriaceae (part of the order Enterobacterales) is associated with subsequent infection, and increased colonization density is associated with increased infection risk. Therefore, colonization offers a window of opportunity for infection prevention if (i) there are rapid and inexpensive assays to detect colonization, (ii) there are safe and effective interventions, and (iii) the risk of infection outweighs the risk of the treatment. Fecal transplants are proof of principle that manipulating the microbiome can reduce such colonization and prevent infections. This study demonstrates the feasibility of implementing rapid and inexpensive assays to quantify colonization and measures the strength of association between Enterobacterales dominance and subsequent infection. The approach described here could be a valuable tool in the prevention of antibiotic-resistant infections.
format	article
author	Krishna Rao Anna Seekatz Christine Bassis Yuang Sun Emily Mantlo Michael A. Bachman
author_facet	Krishna Rao Anna Seekatz Christine Bassis Yuang Sun Emily Mantlo Michael A. Bachman
author_sort	Krishna Rao
title	<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients
title_short	<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients
title_full	<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients
title_fullStr	<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients
title_full_unstemmed	<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients
title_sort	<italic toggle="yes">enterobacterales</italic> infection after intestinal dominance in hospitalized patients
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/5a5055bf1b2c4167a34f76cb633f4abd
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<italic toggle="yes">Enterobacterales</italic> Infection after Intestinal Dominance in Hospitalized Patients

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