Risk of meticillin resistant <i>Staphylococcus aureus</i> and <i>Clostridium difficile</i> in patients with a documented penicillin allergy: population based matched cohort study

Abstract

<h3>Abstract</h3> <h3>Objective</h3> To evaluate the relation between penicillin allergy and development of meticillin resistant <i>Staphylococcus aureus</i> (MRSA) and <i>C difficile</i>. <h3>Design</h3> Population based matched cohort study. <h3>Setting</h3> United Kingdom general practice (1995-2015). <h3>Participants</h3> 301 399 adults without previous MRSA or <i>C difficile</i> enrolled in the Health Improvement Network database: 64 141 had a penicillin allergy and 237 258 comparators matched on age, sex, and study entry time. <h3>Main outcome measures</h3> The primary outcome was risk of incident MRSA and <i>C difficile</i>. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics. <h3>Results</h3> Among 64 141 adults with penicillin allergy and 237 258 matched comparators, 1365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1688 developed <i>C difficile</i> (442 participants with penicillin allergy and 1246 comparators) during a mean 6.0 years of follow-up. Among patients with penicillin allergy the adjusted hazard ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for <i>C difficile</i> was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% confidence interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and 2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of β lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of<i> C difficile</i>. <h3>Conclusions</h3> Documented penicillin allergy was associated with an increased risk of MRSA and <i>C difficile</i> that was mediated by the increased use of β lactam alternative antibiotics. Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of MRSA and <i>C difficile</i> among patients with a penicillin allergy label.