Penicillin allergy associated with risk of MRSA, C. diff, due to use of other antibiotics

Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile among patients with a documented penicillin allergy.


Penicillin allergy was associated with an increased risk of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile that was mediated by the increased use of alternatives to beta-lactam antibiotics, a study found.

To evaluate the relationship between penicillin allergy and MRSA and C. difficile, researchers conducted a population-based, matched-cohort study among general practices in the United Kingdom from 1995 to 2015. There were 301,399 adults without previous MRSA or C. difficile enrolled in the Health Improvement Network database, of whom 64,141 had a penicillin allergy and 237,258 were comparators matched on age, sex, and study entry time.

The study's primary outcome was risk of incident MRSA and C. difficile, while secondary outcomes were use of beta-lactam antibiotics and beta-lactam alternative antibiotics. Results were published June 27 by BMJ.

Among the cohort, 1,365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1,688 developed C. difficile (442 participants with penicillin allergy and 1,246 comparators) during a mean of 6.0 years of follow-up. Among patients with penicillin allergy, the adjusted hazard ratio was 1.69 (95% CI, 1.51 to 1.90) for MRSA and 1.26 (95% CI, 1.12 to 1.40) for C. difficile. The adjusted incidence rate ratios for antibiotic use in this group were 4.15 (95% CI, 4.12 to 4.17) for macrolides, 3.89 (95% CI, 3.66 to 4.12) for clindamycin, and 2.10 (95% CI, 2.08 to 2.13) for fluoroquinolones. Increased use of beta-lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of C. difficile, the authors noted.

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, the authors wrote.

“Use of the most narrow spectrum antibiotic that is effective for a given infection is a cornerstone of evidence based treatment for infection and is responsible antibiotic stewardship,” the researchers wrote. “Antibiotic stewardship committees enforce this aim in the hospital setting, with evaluations for penicillin allergy occasionally included in stewardship efforts. This analysis emphasises the importance of performing outpatient antibiotic stewardship and the role that penicillin allergy evaluations might play.”