Analysis of outpatient records of large number of British patients reveals that those believed to be allergic to penicillin have significantly increased risks of contracting the dangerous infections MRSA (methicillin-resistant Staphylococcus aureus) and Clostridium difficile (C. difficile). The study led by Massachusetts General Hospital (MGH) investigators finds that much of that increased risk can be attributed to the use of broad-spectrum alternative antibiotics, which are known on contribute to the growth of antibiotic-resistant pathogens.

Methicillin-resistant Staphylococcus aureus (MRSA)  Image/NIAID
Methicillin-resistant Staphylococcus aureus (MRSA)

“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,” says Kimberly Blumenthal, MD, MSc, of the MGH Division of Rheumatology, Allergy and Immunology and the Medical Practice Evaluation Center, lead and corresponding author of the report in the June 30 issue of The BMJ. “Our study identifies appropriate penicillin allergy evaluations – 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.

To examine the relationship between a newly recorded penicillin allergy and the risk of subsequent MRSA or C. difficile, the researchers analyzed data from The Health Improvement Network (THIN), a database of outpatient primary care medical records from 11.1 million patients in the U.K. From deidentified data covering the years between 1995 and 2015, the investigators first identified patients with a newly documented penicillin allergy. They then developed a comparison group comprised of up to five individuals for each patient in the penicillin allergy group – matched for age, sex and time of study entry – who also received a penicillin prescription during the study period. They then searched the medical records of both groups for any initial documented diagnoses of MRSA or C. difficile.

The results revealed that patients whose medical records indicated they had a penicillin allergy had a 69 percent greater risk of contracting MRSA than did patients in the comparison group and a 26 percent greater risk of a C. difficile diagnosis during the study period. Both of those risks persisted after controlling for other known risk factors for either infection. More than half the increased MRSA risk and 35 percent of the increased C. difficile risk could be attributed to the antibiotic alternatives to beta-lactams – the antibiotic class that includes penicillin – prescribed to patients believed to be allergic. It is well known that these broad-spectrum antibiotics, which act against many families of bacteria, can both increase the incidence of antibiotic resistance and raise the risk of more virulent infections like C. difficileby killing off beneficial bacteria that populate the gastrointestinal tract.

“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,” says 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.”