van Duijn PJ, et al. - Researchers here investigated if 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). It was noted that among patients admitted to the ICU, no reduction in the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria was there with antibiotic cycling.

Methods

• Researchers undertook a cluster-randomised crossover study.
• ICUs were assigned 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).
• They performed computer-based randomisation of intervention and rotated antibiotic sequence centrally.
• For 9 months, cycling or mixing was applied; then, following a washout period, the alternative strategy was implemented.
• In this work, they 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.
• Collection of data for all admissions was performed during the study.
• Average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders was assessed as the primary endpoint. 

Results

• Random assignment of 8 ICUs (from Belgium, France, Germany, Portugal, and Slovenia) was performed from June 27, 2011, to Feb 16, 2014.
• In total, 4,069 and 4,707 patients were admitted during the cycling periods and the mixing periods, respectively.
• Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys; the main analysis included these patients.
• Mean prevalence of the composite primary endpoint was 23% (168/745) and 22% (184/853) during cycling and during mixing (p=0·64), respectively, yielding an adjusted incidence rate ratio during mixing of 1.039 (95% CI 0.837–1.291; p=0.73).
• No difference in all-cause in-ICU mortality between intervention periods was noted.