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Critical Care
Published in: Critical Care 1/2020

Open Access 01-12-2020 | Septicemia | Research

The effect of short-course antibiotics on the resistance profile of colonizing gut bacteria in the ICU: a prospective cohort study

Authors: Christian Munck, Ravi U. Sheth, Edward Cuaresma, Jessica Weidler, Stephania L. Stump, Philip Zachariah, David H. Chong, Anne-Catrin Uhlemann, Julian A. Abrams, Harris H. Wang, Daniel E. Freedberg

Published in: Critical Care | Issue 1/2020

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Abstract

Background

The need for early antibiotics in the intensive care unit (ICU) is often balanced against the goal of antibiotic stewardship. Long-course antibiotics increase the burden of antimicrobial resistance within colonizing gut bacteria, but the dynamics of this process are not fully understood. We sought to determine how short-course antibiotics affect the antimicrobial resistance phenotype and genotype of colonizing gut bacteria in the ICU by performing a prospective cohort study with assessments of resistance at ICU admission and exactly 72 h later.

Methods

Deep rectal swabs were performed on 48 adults at the time of ICU admission and exactly 72 h later, including patients who did and did not receive antibiotics. To determine resistance phenotype, rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, Gram-negative bacterial isolates were cultured against relevant antibiotics. To determine resistance genotype, quantitative PCR (qPCR) was performed from rectal swabs for 87 established resistance genes. Within-individual changes in antimicrobial resistance were calculated based on culture and qPCR results and correlated with exposure to relevant antibiotics (e.g., did β-lactam antibiotic exposure associate with a detectable change in β-lactam resistance over this 72-h period?).

Results

Of 48 ICU patients, 41 (85%) received antibiotics. Overall, there was no increase in the antimicrobial resistance profile of colonizing gut bacteria during the 72-h study period. There was also no increase in antimicrobial resistance after stratification by receipt of antibiotics (i.e., no detectable increase in β-lactam, vancomycin, or macrolide resistance regardless of whether patients received those same antibiotics). This was true for both culture and PCR. Antimicrobial resistance pattern at ICU admission strongly predicted resistance pattern after 72 h.

Conclusions

Short-course ICU antibiotics made little detectable difference in the antimicrobial resistance pattern of colonizing gut bacteria over 72 h in the ICU. This provides an improved understanding of the dynamics of antimicrobial resistance in the ICU and some reassurance that short-course antibiotics may not adversely impact the stewardship goal of reducing antimicrobial resistance.
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Literature
1.
Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54(11):4851–63.CrossRefPubMed
2.
Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Kumar A, Simon D, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136(5):1237–48.CrossRef
3.
Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, Perez XL, Sirvent JM, Edusepsis Study G. Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med. 2009;180(9):861–6.CrossRef
4.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486–552.CrossRef
5.
Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, Lemeshow S, Osborn T, Terry KM, Levy MM. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235–44.CrossRefPubMed
6.
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–3.CrossRefPubMed
7.
Filius PM, Gyssens IC, Kershof IM, Roovers PJ, Ott A, Vulto AG, Verbrugh HA, Endtz HP. Colonization and resistance dynamics of gram-negative bacteria in patients during and after hospitalization. Antimicrob Agents Chemother. 2005;49(7):2879–86.CrossRefPubMed
8.
Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4554–61.CrossRef
9.
Livanos AE, Snider EJ, Whittier S, Chong DH, Wang TC, Abrams JA, Freedberg DE. Rapid gastrointestinal loss of clostridial clusters IV and XIVa in the ICU associates with an expansion of gut pathogens. PLoS One. 2018;13(8):e0200322.CrossRefPubMed
10.
Terry MA, Freedberg DE, Morris MC. An alternative consent process for minimal risk research in the ICU. Crit Care Med. 2017;45(9):1450–6.CrossRefPubMed
11.
Budding AE, Grasman ME, Eck A, Bogaards JA, Vandenbroucke-Grauls CM, van Bodegraven AA, Savelkoul PH. Rectal swabs for analysis of the intestinal microbiota. PLoS One. 2014;9(7):e101344.CrossRefPubMed
12.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.CrossRefPubMed
13.
Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176(11):1639–48.CrossRef
14.
15.
16.
Rocha DJ, Santos CS, Pacheco LG. Bacterial reference genes for gene expression studies by RT-qPCR: survey and analysis. Antonie Van Leeuwenhoek. 2015;108(3):685–93.CrossRef
17.
Freedberg DE, Salmasian H, Cohen B, Abrams JA, Larson EL. Receipt of antibiotics in hospitalized patients and risk for clostridium difficile infection in subsequent patients who occupy the same bed. JAMA Intern Med. 2016;176(12):1801–8.CrossRefPubMed
18.
Whiles BB, Deis AS, Simpson SQ. Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med. 2017;45(4):623–9.CrossRefPubMed
19.
Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017;196(7):856–63.CrossRefPubMed
20.
Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, Huskins WC, Paterson DL, Fishman NO, Carpenter CF, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159–77.CrossRef
21.
Good BH, McDonald MJ, Barrick JE, Lenski RE, Desai MM. The dynamics of molecular evolution over 60,000 generations. Nature. 2017;551(7678):45–50.CrossRefPubMed
22.
Tenaillon O, Barrick JE, Ribeck N, Deatherage DE, Blanchard JL, Dasgupta A, Wu GC, Wielgoss S, Cruveiller S, Medigue C, et al. Tempo and mode of genome evolution in a 50,000-generation experiment. Nature. 2016;536(7615):165–70.CrossRefPubMed
23.
Lescat M, Launay A, Ghalayini M, Magnan M, Glodt J, Pintard C, Dion S, Denamur E, Tenaillon O. Using long-term experimental evolution to uncover the patterns and determinants of molecular evolution of an Escherichia coli natural isolate in the streptomycin-treated mouse gut. Mol Ecol. 2017;26(7):1802–17.CrossRef
24.
Alverdy JC, Krezalek MA. Collapse of the microbiome, emergence of the pathobiome, and the immunopathology of sepsis. Crit Care Med. 2017;45(2):337–47.CrossRefPubMed
25.
Perez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, et al. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut. 2013;62(11):1591–601.CrossRef
26.
Dubin KA, Mathur D, McKenney PT, Taylor BP, Littmann ER, Peled JU, van den brink MRM, Taur Y, Pamer EG, Xavier JB: Diversification and evolution of vancomycin-resistant Enterococcus faecium during intestinal domination. Infect Immun. 2019;87(7):e00102–19.
27.
Porse A, Gumpert H, Kubicek-Sutherland JZ, Karami N, Adlerberth I, Wold AE, Andersson DI, Sommer MOA. Genome dynamics of Escherichia coli during antibiotic treatment: transfer, loss, and persistence of genetic elements in situ of the infant gut. Front Cell Infect Microbiol. 2017;7:126.CrossRefPubMed
28.
Karami N, Martner A, Enne VI, Swerkersson S, Adlerberth I, Wold AE. Transfer of an ampicillin resistance gene between two Escherichia coli strains in the bowel microbiota of an infant treated with antibiotics. J Antimicrob Chemother. 2007;60(5):1142–5.CrossRef
29.
Gumpert H, Kubicek-Sutherland JZ, Porse A, Karami N, Munck C, Linkevicius M, Adlerberth I, Wold AE, Andersson DI, Sommer MOA. Transfer and persistence of a multi-drug resistance plasmid in situ of the infant gut microbiota in the absence of antibiotic treatment. Front Microbiol. 2017;8:1852.CrossRefPubMed
30.
Urtasun RC, Rabin HR, Partington J. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously. Surgery. 1983;93(1 Pt 2):145–8.
31.
Tulstrup MV, Christensen EG, Carvalho V, Linninge C, Ahrne S, Hojberg O, Licht TR, Bahl MI. Antibiotic treatment affects intestinal permeability and gut microbial composition in wistar rats dependent on antibiotic class. PLoS One. 2015;10(12):e0144854.CrossRefPubMed
32.
Willmann M, Vehreschild M, Biehl LM, Vogel W, Dorfel D, Hamprecht A, Seifert H, Autenrieth IB, Peter S. Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study. BMC Biol. 2019;17(1):76.CrossRefPubMed
33.
Ferreiro A, Crook N, Gasparrini AJ, Dantas G. Multiscale evolutionary dynamics of host-associated microbiomes. Cell. 2018;172(6):1216–27.CrossRefPubMed
34.
Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi de Carvalho F, Paiva JA, Cakar N, Ma X, Eggimann P, et al. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT international cohort study. Intensive Care Med. 2012;38(12):1930–45.CrossRef
35.
Raymond F, Boissinot M, Ouameur AA, Deraspe M, Plante PL, Kpanou SR, Berube E, Huletsky A, Roy PH, Ouellette M, et al. Culture-enriched human gut microbiomes reveal core and accessory resistance genes. Microbiome. 2019;7(1):56.CrossRefPubMed
36.
Walker GT, Quan J, Higgins SG, Toraskar N, Chang W, Saeed A, Sapiro V, Pitzer K, Whitfield N, Lopansri BK, et al. Predicting antibiotic resistance in gram-negative bacilli from resistance genes. Antimicrob Agents Chemother. 2019;63(4):e02462–18.
Metadata
Title
The effect of short-course antibiotics on the resistance profile of colonizing gut bacteria in the ICU: a prospective cohort study
Authors
Christian Munck
Ravi U. Sheth
Edward Cuaresma
Jessica Weidler
Stephania L. Stump
Philip Zachariah
David H. Chong
Anne-Catrin Uhlemann
Julian A. Abrams
Harris H. Wang
Daniel E. Freedberg
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-03061-8

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