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

Objective: To evaluate the relation between penicillin allergy and development of meticillin resistant Staphylococcus aureus (MRSA) and C difficile.

Design: Population based matched cohort study.

Setting: United Kingdom general practice (1995-2015).

Participants: 301 399 adults without previous MRSA or C difficile 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.

Main outcome measures: The primary outcome was risk of incident MRSA and C difficile. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics.

Results: 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 C difficile (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 C difficile 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 C difficile.

Conclusions: Documented penicillin allergy was associated with an increased risk of MRSA and C difficile 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 C difficile among patients with a penicillin allergy label.