Fact checked byKristen Dowd

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October 25, 2024
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Incorrect penicillin allergy labels drive ‘treatment delays’ for patients with syphilis

Fact checked byKristen Dowd
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Key takeaways:

  • All patients in the study were delabeled.
  • One pregnant patient’s pregnancy was complicated by congenital syphilis.
  • Five patients achieved clearance.

BOSTON — Low-risk patients with syphilis and a penicillin allergy label should be delabeled to avoid treatment failure, according to a poster presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

“In talking to patients who were being sent to us for penicillin allergy testing in the context of having syphilis, we noticed that it seemed like many of them had undergone a long road of failed treatments and more intensive treatment procedures before being sent to the allergy clinic,” Cosby A. Stone Jr., MD, MPH, assistant professor of medicine in the division of allergy, pulmonology and critical care medicine at Vanderbilt University Medical Center and VUMC Drug Allergy Research, told Healio.

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“We performed [institutional review board]-approved chart reviews to study that question more directly and gather those stories together into a case series that we could try to learn from, especially since syphilis is on the rise and up to 15% of adults in the United States will report a penicillin allergy that hasn’t been tested,” he continued.

Stone further explained that patients with syphilis need treatment as soon as possible so they do not have a bad outcome from being infected, so they are less likely to pass syphilis along to a partner and, in the case of pregnancy, so they do not pass it on to a baby.

“We want syphilis patients to get effective treatment as soon as possible to prevent them from having any of the irreversible consequences of a syphilis infection, such as neurological damage or heart damage,” he said.

The study consisted of a retrospective review of patients labeled with a penicillin allergy and a confirmed diagnosis of syphilis who were referred to VUMC Drug Allergy Research between January 2014 and January 2024 for assessment and delabeling. Data were collected on patient demographics, syphilis stage, penicillin allergy testing results, use of second-line treatment, health care utilization, penicillin use after delabeling and clearance of syphilis.

Among the 12 patients included in the study (83.3% male; median age, 39 years), nine were treated with doxycycline prior to evaluation, including patients with multiple treatments, with five successful and seven failed treatments.

One patient was treated with ceftriaxone with a failed result. Penicillin desensitization was experienced by three patients in the ICU. A pregnant female patient with penicillin desensitization had her pregnancy complicated by congenital syphilis.

Among the 12 patients, all were delabeled of their penicillin allergy. Subsequent penicillin treatment was documented in nine of them, whereas three did not follow up. The nine patients who took penicillin resulted in five achieving clearance, three who failed clearance and one who had an unknown clearance outcome.

“The main thing that we noticed was that more than half of our patients had failed other antibiotic treatments such as doxycycline before the penicillin allergy testing was even thought of,” Stone said. “A failed treatment in my mind equates to a delay in the amount of time between diagnosis and finally getting an effective treatment and clearance of syphilis, during which other bad things can happen.”

Stone noted that when penicillin treatment was considered, patients had to be hospitalized for desensitization, which does not need to happen if an allergy test is performed.

“In fact, out of 12 syphilis patients that we tested who thought they might have a penicillin allergy, none of them actually had a penicillin allergy,” he said. “That’s what drives our findings and our conclusion that if the patients had been sent for testing sooner, it could have led to avoidance of treatment delays, treatment failures and increased treatment costs. The results remind us of the implications of an untested penicillin allergy when penicillin treatments are the first-line drug.”

Having to use a less effective drug increases the likeliness of a worse outcome, according to Stone.

“One complication that haunts me is that one of our patients had experienced transmission of syphilis to her unborn child and had also failed treatments with second-line drugs,” he said. “When we tested her, she was able to get treated with penicillin successfully, clear her syphilis infection and thereby avoided that outcome for her next pregnancy.”

Stone recommends that doctors should immediately test a penicillin allergy when a syphilis diagnosis is found in someone who reports an allergy. He suggests using a validated penicillin allergy risk assessments, such as PEN-FAST or the Vanderbilt system, and testing the allergy with a single dose amoxicillin challenge at the point of care for low-risk patients.

“We want all patients to be getting first-line antibiotics when they need them, as long as it’s really safe to use those drugs,” he said. “An untested penicillin allergy is a barrier to using first-line treatments for syphilis, because it introduces doubt about whether you can take the right drug at the time you really need it, and most of the time, you probably can if you would just get tested.”

Antibiotic allergies pose a big policy problem for STD treatment, Stone explained.

“Our observations from the study are that patients who report penicillin allergies seem to have to go through a much longer, more expensive, more tumultuous path to get to an effective treatment and cure of syphilis,” he said. “The second-line drugs for syphilis don’t seem to work as well as penicillin. That’s probably why they are second-line. With syphilis cases on the rise right now, we want to bring those cases back down again by using as many first-line treatments as possible.”

Stone urges state public health officials and the CDC to proactively think about how to tackle penicillin allergies.

“Whatever we can do as public health workers and members of the health care team to prevent bad treatment outcomes is something that has very high value in my book,” Stone said.

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