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Possible penicillin allergy link to risk of ‘superbug’ infections

Risk of infections could be modified by prescribing changes

Adrian O'Dowd

Thursday, 28 June 2018

Patients with penicillin allergy listed on their medical records could be at a higher risk of developing the drug resistant “superbug” infection methicillin-resistant Staphylococcus aureus (MRSA) and healthcare-associated infection C. difficile, suggests a study* published by The BMJ.

This risk appears to be mostly due to the use of more “broad spectrum” antibiotics as alternatives to penicillin, said researchers, which may be fuelling the development of drug resistant bacteria.

Penicillin allergy is the most commonly documented drug allergy, reported by about 10% of patients, but previous studies have shown that more than 90% of patients with listed penicillin allergies can be safely treated with penicillins.

Researchers at Massachusetts General Hospital in Boston, USA, set out to evaluate the public health consequences of a penicillin allergy label by examining the relation between penicillin allergy and development of MRSA and C. difficile (Clostridium difficile).

They used data from The Health Improvement Network (THIN) – an electronic general practice database of 11 million UK patients’ records.

From this, they identified 64,141 adults with a documented penicillin allergy and 237,258 matched adults of similar age and sex, with recent penicillin exposure but without a penicillin allergy.

None of the participants had any history of MRSA and C. difficile infection, and were followed up for an average of six years, during which time use of antibiotics and cases of doctor diagnosed MRSA and C. difficile were recorded.

Results showed that 1,345 participants developed MRSA and 1,688 developed C. difficile over the follow-up period.

After taking into account several known risk factors, the researchers found that a penicillin allergy label for a patient was associated with a 69% increased risk of MRSA and a 26% increased risk of C. difficile.

Once documented, a penicillin allergy was associated with increased use of alternative “broad spectrum” antibiotics, which act against a wider range of bacteria.

Analysis showed that among patients with a listed penicillin allergy, increased use of “broad spectrum” antibiotics accounted for more than half (55%) of the increased MRSA risk and more than one-third (35%) of the increased C. difficile risk.

This was an observational study, so no firm conclusions could be drawn about cause and effect, and the researchers could not rule out the possibility that other, unmeasured factors may have affected their results.

However, they pointed out that this was a large, representative sample and the findings remained consistent after further analyses to test the strength of the results.

They concluded: “Patients with a documented penicillin allergy have an increased risk of new MRSA and C. difficile that may be modifiable, to some degree, through changes in antibiotic prescribing.

“As infections with resistant organisms increase, systematic efforts to confirm or rule out the presence of true penicillin allergy may be an important public health strategy to reduce the incidence of MRSA and C. difficile.”


*Blumenthal, K; Zhang, Y; Li, Y; Walensky, R; and Choi, H. Risk of methicillin-resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population-based matched cohort study. BMJ 2018;361:k2400. DOI:10.1136/bmj.k2400

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