Effects of Antibiotic Cycling Policy on Incidence of Healthcare-Associated MRSA and Clostridioides difficile Infection in Secondary Healthcare Settings

Geraldine Mary Conlon-Bingham; Mamoon Aldeyab; Michael Scott; Mary Patricia Kearney; David Farren; Fiona Gilmore; James McElnay


Emerging Infectious Diseases. 2019;25(1):52-62. 

In This Article

Abstract and Introduction


This quasi-experimental study investigated the effect of an antibiotic cycling policy based on time-series analysis of epidemiologic data, which identified antimicrobial drugs and time periods for restriction. Cyclical restrictions of amoxicillin/clavulanic acid, piperacillin/tazobactam, and clarithromycin were undertaken over a 2-year period in the intervention hospital. We used segmented regression analysis to compare the effect on the incidence of healthcare-associated Clostridioides difficile infection (HA-CDI), healthcare-associated methicillin-resistant Staphylococcus aureus(HA-MRSA), and new extended-spectrum β-lactamase (ESBL) isolates and on changes in resistance patterns of the HA-MRSA and ESBL organisms between the intervention and control hospitals. HA-CDI incidence did not change. HA-MRSA incidence increased significantly in the intervention hospital. The resistance of new ESBL isolates to amoxicillin/clavulanic acid and piperacillin/tazobactam decreased significantly in the intervention hospital; however, resistance to piperacillin/tazobactam increased after a return to the standard policy. The results question the value of antibiotic cycling to antibiotic stewardship.


Restrictive antimicrobial prescribing guidelines have successfully reduced the incidence of Clostridioides difficile infection (CDI; formerly Clostridium difficile) and methicillin-resistant Staphylococcus aureus (MRSA).[1–6] However, these guidelines have been suggested to create an environment of antimicrobial homogeneity that may enhance the development and spread of antimicrobial resistance.[7,8] Antibiotic cycling has been proposed as an effective strategy to increase antimicrobial heterogeneity and decrease the development of antimicrobial resistance.[8,9] This method of increasing antimicrobial heterogeneity has had mixed effects on antimicrobial resistance; however, investigations have been conducted mainly in intensive care units (ICUs) and in patients with specific infections (neutropenic sepsis, ventilator-associated pneumonia), and cycling periods have been arbitrarily defined, ranging from 1 week to 6 months.[10–22] In a meta-analysis of studies investigating antibiotic cycling, the optimal cycling period was identified as 30 days.[23] When the cycling period is too long, the effect becomes equivalent to continuous use of a single agent, increasing antimicrobial homogeneity.

We aimed to evaluate the effect of an antibiotic cycling policy, derived using time-series analysis of retrospective epidemiologic data, on the incidence of healthcare-associated MRSA (HA-MRSA) and healthcare-associated CDI (HA-CDI). A secondary aim was to evaluate the effect of this policy on the incidence of infections caused by extended-spectrum β-lactamase (ESBL)–producing organisms.