Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial.
Administration, Oral
Aged
Antibiotic Prophylaxis
Colistin
/ administration & dosage
Colorectal Surgery
/ adverse effects
Double-Blind Method
Female
Humans
Incidence
Male
Middle Aged
Netherlands
/ epidemiology
Surgical Wound Infection
/ epidemiology
Therapeutic Equipoise
Tobramycin
/ administration & dosage
Colorectal surgery
Infection control
Preoperative oral antibiotic prophylaxis
Surgical site infection
Journal
Antimicrobial resistance and infection control
ISSN: 2047-2994
Titre abrégé: Antimicrob Resist Infect Control
Pays: England
ID NLM: 101585411
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
24
03
2020
accepted:
29
05
2020
entrez:
17
6
2020
pubmed:
17
6
2020
medline:
2
4
2021
Statut:
epublish
Résumé
Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46). Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17.
Sections du résumé
BACKGROUND
Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown.
METHODS
The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery.
RESULTS
The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23-2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12-3.46).
CONCLUSIONS
Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities.
TRIAL REGISTRATION
The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015-005736-17.
Identifiants
pubmed: 32539786
doi: 10.1186/s13756-020-00745-2
pii: 10.1186/s13756-020-00745-2
pmc: PMC7294517
doi:
Substances chimiques
Tobramycin
VZ8RRZ51VK
Colistin
Z67X93HJG1
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
84Références
Int Wound J. 2004 Dec;1(4):247-73
pubmed: 16722874
Cochrane Database Syst Rev. 2014 May 09;(5):CD001181
pubmed: 24817514
Ann Surg. 2018 Apr;267(4):734-742
pubmed: 28151800
Tech Coloproctol. 2011 Dec;15(4):385-95
pubmed: 21785981
Lancet Infect Dis. 2013 Apr;13(4):328-41
pubmed: 23352693
J Clin Microbiol. 2015 Aug;53(8):2709-12
pubmed: 25994164
J Gastrointest Surg. 2017 Feb;21(2):372-379
pubmed: 27896654
J Antimicrob Chemother. 2014 Mar;69(3):797-804
pubmed: 24144922
J Am Coll Surg. 2017 Oct;225(4):465-471
pubmed: 28690206
J Visc Surg. 2016 Apr;153(2):85-7
pubmed: 26526212
Int J Colorectal Dis. 2018 Dec;33(12):1781-1791
pubmed: 30238356
Am J Infect Control. 1992 Oct;20(5):271-4
pubmed: 1332552
Ann Surg. 2015 Aug;262(2):331-7
pubmed: 26083870
Intensive Care Med. 2013 Apr;39(4):653-60
pubmed: 23203301
N Engl J Med. 1987 Jul 16;317(3):141-5
pubmed: 3600702
Trials. 2018 Jan 19;19(1):51
pubmed: 29351789
Surg Infect (Larchmt). 2015 Dec;16(6):728-32
pubmed: 26230616
J Hosp Infect. 2017 May;96(1):1-15
pubmed: 28410761
J Hosp Infect. 2018 Dec;100(4):400-405
pubmed: 30125586
J Am Coll Surg. 2015 May;220(5):912-20
pubmed: 25907871
Arch Surg. 2005 Feb;140(2):174-82
pubmed: 15724000
Crit Care. 2015 Mar 25;19:113
pubmed: 25880968
J Hosp Infect. 2005 Jun;60(2):93-103
pubmed: 15866006
Dis Colon Rectum. 2017 Jul;60(7):729-737
pubmed: 28594723
Cochrane Database Syst Rev. 2011 Sep 07;(9):CD001544
pubmed: 21901677
J Hosp Infect. 2001 Aug;48(4):267-74
pubmed: 11461127
BJS Open. 2018 May 10;2(4):238-245
pubmed: 30079393
Langenbecks Arch Surg. 2011 Apr;396(4):453-9
pubmed: 21404004
Surgery. 2018 Mar;163(3):528-534
pubmed: 29198768
Ann Surg. 2004 May;239(5):599-605; discussion 605-7
pubmed: 15082963
Clin Infect Dis. 2019 Jun 18;69(1):93-99
pubmed: 30281072
Ann Surg. 1973 Oct;178(4):453-62
pubmed: 4743867
Colorectal Dis. 2017 Sep;19(9):832-839
pubmed: 28436176
PLoS Med. 2016 Oct 18;13(10):e1002150
pubmed: 27755545