The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial - Université de Versailles Saint-Quentin-en-Yvelines Access content directly
Journal Articles The Lancet Infectious Diseases Year : 2018

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial

Pleun Joppe van Duijn
  • Function : Author
Walter Verbrugghe
  • Function : Author
Philippe Germaine Jorens
  • Function : Author
Fabian Spöhr
  • Function : Author
Dirk Schedler
  • Function : Author
Maria Deja
  • Function : Author
Andreas Rothbart
  • Function : Author
Jean-Claude Nguyen Van
  • Function : Author
Benoit Misset
  • Function : Author
Matjaz Jereb
  • Function : Author
Katja Seme
  • Function : Author
Franc Šifrer
  • Function : Author
Viktorija Tomiç
  • Function : Author
Francisco Estevez
  • Function : Author
Jandira Carneiro
  • Function : Author
Stephan Harbarth
  • Function : Author
Marc Bonten
  • Function : Author
Herman Goossens
  • Function : Author
Surbhi Malhotra-Kumar
  • Function : Author
Christine Lammens
  • Function : Author
Jordi Vila
  • Function : Author
Ignaci Roca
  • Function : Author

Abstract

Background Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). Methods In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin–tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum β-lactamase production or piperacillin–tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin– tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. Findings Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837–1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. Interpretation Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU.

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hal-04533970 , version 1 (05-04-2024)

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Pleun Joppe van Duijn, Walter Verbrugghe, Philippe Germaine Jorens, Fabian Spöhr, Dirk Schedler, et al.. The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial. The Lancet Infectious Diseases, 2018, 18 (4), pp.401-409. ⟨10.1016/S1473-3099(18)30056-2⟩. ⟨hal-04533970⟩
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