Evelien A N Oostdijk1, Jozef Kesecioglu2, Marcus J Schultz3, Caroline E Visser4, Evert de Jonge5, Einar H R van Essen5, Alexandra T Bernards6, Ilse Purmer7, Roland Brimicombe8, Dennis Bergmans9, Frank van Tiel10, Frank H Bosch11, Ellen Mascini12, Arjanne van Griethuysen12, Alexander Bindels13, Arjan Jansz14, Fred A L van Steveninck15, Wil C van der Zwet16, Jan Willem Fijen17, Steven Thijsen18, Remko de Jong19, Joke Oudbier20, Adrienne Raben21, Eric van der Vorm22, Mirelle Koeman7, Philip Rothbarth23, Annemieke Rijkeboer24, Paul Gruteke25, Helga Hart-Sweet26, Paul Peerbooms27, Lex J Winsser28, Anne-Marie W van Elsacker-Niele29, Kees Demmendaal30, Afke Brandenburg29, Anne Marie G A de Smet31, Marc J M Bonten32. 1. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht2Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht. 2. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht. 3. Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam. 4. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam. 5. Department of Intensive Care Medicine, Leiden University Medical Center, Leiden. 6. Department of Medical Microbiology, Leiden University Medical Center, Leiden. 7. Department of Intensive Care, HagaZiekenhuis, The Hague. 8. Department of Medical Microbiology, HagaZiekenhuis, The Hague. 9. Department of Intensive Care, Maastricht University Medical Centre+, Maastricht. 10. Department of Medical Microbiology, Maastricht University Medical Centre+, Maastricht. 11. Department of Intensive Care, Rijnstate Hospital, Arnhem. 12. Laboratory for Medical Microbiology and Immunology, Rijnstate Hospital, Arnhem. 13. Department of Intensive Care Medicine, Catharina Hospital, Eindhoven. 14. Laboratory for Medical Microbiology, Laboratories for Pathology and Medical Microbiology, Catharina Hospital, Eindhoven. 15. Department of Intensive Care, Deventer Hospital, Deventer. 16. Department of Medical Microbiology, Deventer Hospital, Deventer. 17. Department of Intensive Care, Diakonessenhuis Utrecht, Utrecht. 18. Department of Medical Microbiology, Diakonessenhuis Utrecht, Utrecht. 19. Department of Intensive Care, BovenIJ Hospital, Amsterdam. 20. Department of Medical Microbiology, Zaans Medical Center, Zaandam. 21. Department of Intensive Care, Groene Hart Hospital, Gouda. 22. Department of Medical Microbiology, Groene Hart Hospital, Gouda. 23. Department of Medical Microbiology, Rijnland Hospital, Leiderdorp. 24. Department of Intensive Care, Flevo Hospital, Almere. 25. Department of Medical Microbiology, Flevo Hospital, Almere. 26. Department of Intensive Care, Sint Lucas Andreas Hospital, Amsterdam. 27. Department of Medical Microbiology, Sint Lucas Andreas Hospital, Amsterdam. 28. Department of Intensive Care, Antonius Hospital, Sneek. 29. Izore, Centre for Infectious Diseases Friesland, Leeuwarden. 30. Nij Smellinghe Hospital, Drachten. 31. Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen. 32. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht32Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Abstract
IMPORTANCE: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE: To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS:Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES: Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS: In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE: Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION: trialregister.nlIdentifier: NTR1780.
RCT Entities:
IMPORTANCE: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE: To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5881 and 6116 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS: Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES: Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS: In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.4% and 24.1% during SOD and SDD, respectively (adjusted odds ratio, 0.96 [95% CI, 0.88-1.06]; P = .42), and there were no statistically significant differences in other outcome parameters or between surgical and nonsurgical patients. Intensive care unit-acquired bacteremia occurred in 5.9% and 4.6% of the patients during SOD and SDD, respectively (odds ratio, 0.77 [95% CI, 0.65-0.91]; P = .002; number needed to treat, 77). CONCLUSIONS AND RELEVANCE: Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance and no differences in day-28 mortality. Compared with SOD, SDD was associated with lower rectal carriage of antibiotic-resistant gram-negative bacteria and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION: trialregister.nlIdentifier: NTR1780.
Authors: Celine S Gathier; Evelien A Oostdijk; Gabriel J E Rinkel; Sanne M Dorhout Mees; Mervyn D I Vergouwen; Anne Marie G A de Smet; Diederik van de Beek; W Peter Vandertop; Dagmar Verbaan; Ale Algra; Marc J M Bonten; Walter M van den Bergh Journal: Neurocrit Care Date: 2016-02 Impact factor: 3.210
Authors: Lieuwe D Bos; Cheryl Stips; Laura R Schouten; Lonneke A van Vught; Maryse A Wiewel; Luuk Wieske; Roosmarijn T van Hooijdonk; Marleen Straat; Friso M de Beer; Gerie J Glas; Caroline E Visser; Evert de Jonge; Nicole P Juffermans; Janneke Horn; Marcus J Schultz Journal: Intensive Care Med Date: 2017-05-11 Impact factor: 17.440