Residual effect of community antimicrobial exposure on risk of hospital onset healthcare associated Clostridioides difficile infection: a case-control study using national linked data

Background: Associations between antimicrobial exposure in the community and community-associated Clostridioides difficile infection (CA-CDI) are well documented but associations with healthcare-associated CDI (HA-CDI) are less clear. This study estimates the association between antimicrobial prescribing in the community and HA-CDI. Methods: A matched case–control study was conducted by linking three national patient level datasets covering CDI cases, community prescriptions and hospitalizations. All validated cases of HA-CDI (August 2010 to July 2013) were extracted and up to three hospital-based controls were matched to each case on the basis of gender, age, hospital and date of admission. Conditional logistic regression was applied to estimate the association between antimicrobial prescribing in the community and HA-CDI. A sensitivity analysis was conducted to consider the impact of unmeasured hospital antimicrobial prescribing. Results: Nine-hundred and thirty unique cases of HA-CDI with onset in hospital and no hospital discharge in the 12 weeks prior to index admission were linked with 1810 matched controls. Individuals with prior prescription of any antimicrobial in the community had an odds ratio (OR) = 1.41 (95% confidence interval (CI) 1.13–1.75) for HA-CDI compared with those without. Individuals exposed to high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR = 1.86 (95% CI: 1.33–2.59). After accounting for the likely impact of unmeasured hospital prescribing, the community exposure, particulary to high-risk antimicrobials, was still associated with elevated HA-CDI risk. Conclusions: Community antimicrobial exposure is an independent risk factor for HA-CDI and should be considered as part of the risk assessment of patients developing diarrhoea in hospital.