Antibiotic cycling did not reduce the prevalence of antibiotic-resistant Gram-negative bacteria among patients in European intensive care units (ICUs), according to findings published in the Lancet Infectious Diseases.
Eight ICUs from Belgium, France, Germany, Portugal, and Slovenia were enrolled in a cluster-randomized crossover study (Clinicaltrial.gov: NCT01293071) from June 2011 to February 2014. Each ICU was randomly assigned to an antibiotic cycling regimen (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems as preferred treatment for 6-week periods), or a mixing regimen (changing preference after every consecutively treated patient). Cycling or mixing regimens were in place for 9 months, followed by a washout period and implementation of an alternative strategy. The primary end point was average, unit-wide, monthly point prevalence of antibiotic-resistant Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders.
Numbers of patients present during monthly, point-prevalence surveys in the cycling and mixing trials were 745 and 853, respectively. Mean prevalence of patients with antibiotic-resistant infection was 23% during cycling and 22% during mixing (P =.64), resulting in an adjusted incidence rate ratio during mixing of 1.039 (95% CI, 0.837-1.291; P =.73). No differences in all-cause ICU mortality were observed between intervention periods.
Results from this study provide no evidence for recommendations of one strategy over the other or for either to be recommended to ICUs. Investigators note that the study was underpowered for subgroup analysis of individual resistance and species subtypes, and these factors need to be taken into account when interpreting the results. “Controlling the emergence of antibiotic-resistant Gram-negative bacteria in ICUs is important, but universally useful and successful strategies remain to be identified,” concluded the researchers.
van Duijn PJ, Verbrugghe W, Jorens PG, et al. SATURN consortium. The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial [published online January 24, 2018]. Lancet Infect Dis. doi: 10.1016/S1473-3099(18)30056-2