Increase attributable to use of alternative antibiotics

Patients with general practitioner-reported penicillin allergies had an increased risk for developing methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile (C. difficile) infections mediated by increased use of beta-lactam alternative antibiotics, researchers reported here.

Findings from the newly reported study suggest that addressing patient over-reporting of penicillin allergies could prove to be an effective strategy for reducing MRSA and C. difficile incidence, researchers say.

Kimberly Blumenthal, MD, of Massachusetts General Hospital in Boston, reported the study findings during a presentation at a joint meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the World Allergy Organization (WAO).

Blumenthal and colleagues used mediation analysis to estimate the impact of a new penicillin allergy documentation by a general physician on the use of alternative antibiotics and risk of MRSA and C. difficile over 6 years of patient follow-up.

“We found that over a quarter to half of the risk of new infection was attributable to the alternative antibiotics,” Blumenthal told MedPage Today, adding that the study is the first to show a link between new-onset use of antibiotics and a first documentation of MRSA or C. difficile.

Since the patients did not undergo formal testing to confirm their penicillin allergy, many may have needlessly been taking the alternative antibiotics, she said.

Asked for his perspective, David Lang, MD, chairman of the Department of Allergy and Clinical Immunology and director of the Allergy/Immunology Fellowship Training Program at the Cleveland Clinic, who was not involved with the study, told MedPage Today that there is growing evidence that patient over-reporting of penicillin allergy has very real clinical consequences.

While approximately one in 10 people self-report having a penicillin allergy, studies suggest that only perhaps one in 20 actually have a clinically confirmable intolerance to the drug, he said. “As many as 19 in 20 people avoiding penicillin are doing so needlessly. These people are given alternative antibiotics that are more costly, have more side effects, and predispose them to untoward outcomes.”

Lang said the newly reported research provides further evidence that a label of penicillin allergy is not clinically benign: “A large focus of the antibiotic stewardship initiative is to limit the use of these broad-spectrum antibiotics when we can. It is clear that the low-hanging fruit of antibiotic stewardship is de-labeling these people who believe they have penicillin allergy, but don’t.”

For the study, Blumenthal and colleagues used a general practice database in the United Kingdom with patient data spanning 1995 through 2015, and studied a matched cohort of adults without prior MRSA or C. difficile.

Patients with incident penicillin allergy, as reported in their medical records, were matched with up to five penicillin users without allergy by age, sex, and index date.

The researchers calculated relative risks (RRs) for the association of penicillin allergy with incident MRSA and C. difficile, adjusting for potential confounders, and also examined beta-lactam alternative antibiotic use to determine whether it was a mediator for MRSA/C. difficile incidence.

Over a mean follow-up of 6 years, among 64,141 penicillin allergy patients and 237,258 matched comparators, 1,345 developed MRSA and 1,688 developed C. difficile.

Among the main study findings:

• The adjusted RRs among penicillin allergy patients were 1.62 (95% CI, 1.42-1.85) for MRSA and 1.27 (95% CI, 1.13-1.43) for C. difficile
• The adjusted RRs for antibiotic use among penicillin allergy patients were 4.08 (95% CI, 4.05-4.10) for macrolides, 3.73 (95% CI, 3.51-3.97) for clindamycin, and 2.13 (95% CI, 2.10- 2.16) for fluoroquinolones
• Increased beta-lactam alternative antibiotic use accounted for 53% of the increased MRSA risk and 25% of the increased C. difficile risk

“The message from this research and other research to general practitioners, medical specialists, and surgeons is that when they see a patient with a label of penicillin allergy, send them to us to confirm or disprove this label,” Lang said. “Nine out of 10 — or even 19 of 20 — times we will be able to reduce the patient’s risk for bad outcomes by removing this label.”