Boston—When patients report that they are allergic to penicillin, they often are prescribed broad-spectrum antibiotics as an alternative.

Now, a new study warns of a dangerous unintended consequence: a significantly increased risk for methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile

The findings, published in The BMJ, were based on analysis of more than 11 million outpatient records in Britain. The study, led by Massachusetts General Hospital researchers, attributes much of the increased risk to broad-spectrum antibiotics, which are known to contribute to the growth of antibiotic-resistant pathogens.

“We know that more than 95 percent of patients with an indication of a penicillin allergy in their medical record are found not to be truly allergic, if tested by an allergist,” pointed out lead author Kimberly Blumenthal, MD, MSc. “Our study identifies appropriate penicillin allergy evaluation—which is still done in less than 1 percent of patients with recorded penicillin allergy—as an essential contributor to the globally important outcomes of antibiotic stewardship, reducing antibiotic resistance and health-care-associated infections.”

Data for the study came from The Health Improvement Network (THIN), a database of outpatient primary care medical records from 11.1 million patients in the UK. Patients with newly documented penicillin allergy were identified from records between 1995 and 2015 and were compared to five other Britons, matched for age, sex, and time of study entry, who received penicillin prescriptions. At the same time, diagnoses of MRSA or C difficile were tracked.

Results indicated that patients who said they had a penicillin allergy, as documented in the records, had a 69% greater chance of being diagnosed with MRSA and a 26% greater risk of getting a C difficile diagnosis than patients in the comparison group.

Specifically, among 64,141 adults reporting penicillin allergy and 237,258 matched individuals, 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 an average 6 years of follow-up, the study revealed.

For patients with the reported penicillin allergy, the adjusted hazard ratio was 1.69 (95% confidence interval 1.51 to 1.90) for MRSA and 1.26 for C difficile  (1.12 to 1.40), the article notes.

Study authors suggest that 55% of the increased MRSA risk and 35% of the increased C difficile risk could be attributed to antibiotics prescribed as alternatives to beta-lactams. The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% CI 4.12-4.17) for macrolides, 3.89 (3.66 -4.12) for clindamycin, and 2.10 (2.08-2.13) for fluoroquinolones, the study reports.

“Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of beta-lactam alternative antibiotics,” the researchers conclude. “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.”

“Both MRSA and C difficile infections are increasing public health burdens, are challenging to treat, and cause the deaths of thousands of patients every year,” added Blumenthal, an assistant professor of Medicine at Harvard Medical School. “We now can see a causal path from patients being labeled as having a penicillin allergy, to their being prescribed beta-lactam alternative antibiotics, to greater incidence of these dangerous and costly infections. MRSA and C difficile each cost our health care system more than $1 billion in direct costs annually, so the modest cost of penicillin allergy evaluation—around $220 per patient—seems greatly worthwhile.”

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