Penicillin Allergy Testing Could Reduce C. diff, MRSA Risks


Researchers found that patients with a documented penicillin allergy were at increased risk of developing MRSA (60%) and C. difficile (20%), in part due to alternative antibiotic use. However, when tested by an allergist, 95% were not actually allergic to penicillin.

Kimberly Blumenthal, MD

Kimberly Blumenthal, MD

Patients with a penicillin allergy are at an increased risk for developing Clostridium difficile (C. difficile) or methicillin resistant Staphylococcus aureus (MRSA) infections, according to recent findings. However, the infections were mediated by antibiotics.

Researchers from Boston used data from more than 300,000 patients enrolled in the United Kingdom’s Health Improvement Network database in order to determine MRSA and C. difficile rates, and how they were treated. There were 64,141 patients with a penicillin allergy matched to 237,258 patients based on age, sex, and study entry time, which was between 1995 and 2015.

The study authors noted that those with a penicillin allergy may not be allergic, per se: “After evaluation by an allergist, about 95% of patients with reported penicillin allergies were found to be penicillin tolerant.” They added that a majority of those with hypersensitivities to penicillin are likely no longer allergic after 10 years, and they avoid penicillin unnecessarily.

During a mean 6 years of follow-up, there were 1365 patients who developed MRSA (442 with a penicillin allergy and 923 without) and 1688 patients who developed C. difficile infection (442 with a penicillin allergy and 1246 without).

Based on this data, the researchers determined that patients with a penicillin allergy had more than a 60% increased risk of developing MRSA and a 20% increased risk of developing C. difficile infection.

“What was most interesting was being able to assess whether the increased risk observed was attributed to the observed use of outpatient alternative prescription antibiotics,” study author Kimberly Blumenthal, MD, MSc told MD Magazine.

The investigators also set out to understand how to mediate these infections in patients with a penicillin allergy. C. difficile and MRSA cases were treated with β lactam alternative antibiotic classes, which were generally successful.

“Using a mediation analysis, which is a type of causal inference analysis, we found that the 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, with fluoroquinolones alone responsible for 24% of the heightened MRSA risk and 16% of the heightened C. difficile risk,” Dr. Blumenthal continued.

Proper penicillin allergy evaluations are only done in less than 1% of patients with a recorded penicillin allergy, the researchers said, and that itself can impact global outcomes of antibiotic stewardship. Such tests may cost about $220 per patient, which seems “greatly worthwhile” in attempting to outsmart the annual cost of MRSA and C. difficile—about $1 billion in direct costs, according to the study authors.

“Physicians should consider allergy testing for patients with a penicillin allergy label, particularly those who receive beta-lactam alternative antibiotics such as the fluoroquinolones,” Dr. Blumenthal concluded.

The paper, “Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study,” was published in the BMJ.

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