Each Additional Day of Antibiotics Is Associated With Lower Gut Anaerobes in Neonatal Intensive Care Unit Patients.
anaerobes
antibiotic duration
gut microbiome
neonates
stewardship
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
10 06 2020
10 06 2020
Historique:
received:
30
04
2019
accepted:
22
07
2019
pubmed:
2
8
2019
medline:
7
1
2021
entrez:
2
8
2019
Statut:
ppublish
Résumé
Discontinuation of inappropriate antimicrobial therapy is an important target for stewardship intervention. The drug and duration-dependent effects of antibiotics on the developing neonatal gut microbiota needs to be precisely quantified. In this retrospective, cross-sectional study, we performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit patients within 7 days of discontinuation of therapy who received ampicillin and tobramycin (AT), ampicillin and cefotaxime (AC), or ampicillin, tobramycin, and metronidazole (ATM). We compared taxonomic composition within term and preterm infant groups between treatment regimens. We calculated adjusted effect estimates for antibiotic type and duration of therapy on the richness of obligate anaerobes and known butyrate-producers in all infants. A total of 72 infants were included in the study. Term infants received AT (20/28; 71%) or AC (8/28; 29%) with median durations of 3 and 3.5 days, respectively. Preterm infants received AT (32/44; 73%) or ATM (12/44; 27%) with median durations of 4 and 7 days, respectively. Compositional analyses of 67 stool swab samples demonstrated low diversity and dominance by potential pathogens. Within 1 week of discontinuation of therapy, each additional day of antibiotics was associated with lower richness of obligate anaerobes (adjusted risk ratio [aRR], 0.84; 95% confidence interval [CI], .73-.95) and butyrate-producers (aRR, 0.82; 95% CI, .67-.97). Each additional day of antibiotics was associated with lower richness of anaerobes and butyrate-producers within 1 week after therapy. A longitudinally sampled cohort with preexposure sampling is needed to validate our results.
Sections du résumé
BACKGROUND
Discontinuation of inappropriate antimicrobial therapy is an important target for stewardship intervention. The drug and duration-dependent effects of antibiotics on the developing neonatal gut microbiota needs to be precisely quantified.
METHODS
In this retrospective, cross-sectional study, we performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit patients within 7 days of discontinuation of therapy who received ampicillin and tobramycin (AT), ampicillin and cefotaxime (AC), or ampicillin, tobramycin, and metronidazole (ATM). We compared taxonomic composition within term and preterm infant groups between treatment regimens. We calculated adjusted effect estimates for antibiotic type and duration of therapy on the richness of obligate anaerobes and known butyrate-producers in all infants.
RESULTS
A total of 72 infants were included in the study. Term infants received AT (20/28; 71%) or AC (8/28; 29%) with median durations of 3 and 3.5 days, respectively. Preterm infants received AT (32/44; 73%) or ATM (12/44; 27%) with median durations of 4 and 7 days, respectively. Compositional analyses of 67 stool swab samples demonstrated low diversity and dominance by potential pathogens. Within 1 week of discontinuation of therapy, each additional day of antibiotics was associated with lower richness of obligate anaerobes (adjusted risk ratio [aRR], 0.84; 95% confidence interval [CI], .73-.95) and butyrate-producers (aRR, 0.82; 95% CI, .67-.97).
CONCLUSIONS
Each additional day of antibiotics was associated with lower richness of anaerobes and butyrate-producers within 1 week after therapy. A longitudinally sampled cohort with preexposure sampling is needed to validate our results.
Identifiants
pubmed: 31367771
pii: 5542351
doi: 10.1093/cid/ciz698
pmc: PMC7286368
doi:
Substances chimiques
Anti-Bacterial Agents
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2553-2560Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Pharmacotherapy. 2019 Mar;39(3):261-270
pubmed: 30506852
Science. 2016 Apr 29;352(6285):535-8
pubmed: 27126035
Nat Methods. 2016 Jul;13(7):581-3
pubmed: 27214047
Gut. 2019 Feb;68(2):218-225
pubmed: 29321166
Science. 2013 Aug 2;341(6145):569-73
pubmed: 23828891
ISME J. 2012 Mar;6(3):610-8
pubmed: 22134646
Semin Perinatol. 2012 Dec;36(6):431-6
pubmed: 23177802
Sci Transl Med. 2016 Jun 15;8(343):343ra82
pubmed: 27306664
Science. 2016 Apr 29;352(6285):539-44
pubmed: 27126036
Microbiome. 2017 Mar 9;5(1):31
pubmed: 28274256
JAMA Surg. 2019 Jul 1;154(7):590-598
pubmed: 31017647
Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12522-7
pubmed: 25114261
Pediatrics. 2015 May;135(5):826-33
pubmed: 25896845
ISME J. 2016 Mar;10(3):707-20
pubmed: 26359913
Anaerobe. 2016 Dec;42:119-122
pubmed: 27725229
Sci Transl Med. 2015 Sep 30;7(307):307ra152
pubmed: 26424567
Science. 2017 Aug 11;357(6351):570-575
pubmed: 28798125
Int J Obes (Lond). 2011 Apr;35(4):522-9
pubmed: 21386800
Microbiome. 2017 Jul 12;5(1):75
pubmed: 28701177
Immunity. 2019 May 21;50(5):1276-1288.e5
pubmed: 30902637
Cell Host Microbe. 2015 May 13;17(5):662-71
pubmed: 25865369
Cell Host Microbe. 2015 May 13;17(5):690-703
pubmed: 25974306
ISME J. 2012 Aug;6(8):1621-4
pubmed: 22402401
Nature. 2013 Dec 19;504(7480):451-5
pubmed: 24226773
Biol Blood Marrow Transplant. 2018 Dec;24(12):2418-2424
pubmed: 30055351
J Antimicrob Chemother. 2017 Jul 1;72(7):1858-1870
pubmed: 28369594
BMC Pediatr. 2012 Dec 21;12:196
pubmed: 23259701
FEMS Microbiol Ecol. 2012 Mar;79(3):763-72
pubmed: 22126419
PLoS One. 2016 Apr 25;11(4):e0152751
pubmed: 27111847
BMC Pediatr. 2014 Aug 27;14:212
pubmed: 25164768
J Antimicrob Chemother. 2018 Mar 1;73(3):569-580
pubmed: 29182785
Pediatrics. 2019 Mar;143(3):
pubmed: 30819968
Pediatr Infect Dis J. 2016 Jan;35(1):1-6
pubmed: 26368059