Women should consider penicillin allergy evaluation before or during pregnancy, expert says

Key takeaways:

• Penicillin allergy delabeling is recommended for low-risk pregnant patients.
• Breastfeeding is not an absolute contraindication to drug allergy evaluation. 
• More data are needed for non-penicillin antibiotic allergy evaluation.

BOSTON — The lack of data evaluating the clinical manifestations of adverse drug reactions before and during pregnancy shows need for more research in this area for this patient population, according to Ruchi Shah, MD, FACAAI, FAAAAI.

“The true incidence of adverse drug reactions during pregnancy is unknown, but some studies estimate the incidence to be around 10%,” Shah, staff physician at Cleveland Clinic and assistant professor of medicine at Cleveland Clinic Lerner College of Medicine, said during her presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting. “Pharmacokinetics of drugs can be altered during pregnancy due to changes in absorption, increased volume of distribution, increased metabolic rate and changes in renal excretion.”

She also noted that eight in 10 medications prescribed during pregnancy are antibiotics — a class of medications which can be a commonly implicated allergy in pregnancy.

‘Unique population’

Pregnant patients are a unique population and it is important to consider the different indications for antibiotic use during pregnancy, according to Shah.

“During pregnancy, even asymptomatic bacteruria is treated, typically with beta lactam antibiotics,” she said. “Syphilis is also an important consideration [for antibiotic use] and typically the best treatment is penicillin. During the labor and delivery process, nearly one in three pregnancies are also complicated by group B strep [GBS] which needs to be treated with antibiotics — penicillin typically — and one in three pregnancies are affected by a cesarean section for which [antibiotic] prophylaxis is necessary, usually with cefazolin.”

Other common indications for antibiotic use during pregnancy include chorioamnionitis and endometritis, which can occur during the labor and delivery timeframe.

“In the postpartum timeframe, considerations for mastitis and cesarean section complications also need to be considered,” Shah said.

She then cited a 2021 systematic review by Carra and colleagues that showed antibiotics, latex and anesthetic agents as common triggers of anaphylaxis during pregnancy.

“The most common antibiotic triggers included surgical site infection prophylaxis before cesarean section and GBS prophylaxis during labor,” Shah said. “Other reported agents included oxytocin, intravenous iron, laminaria and misoprostol.”

Anaphylaxis during pregnancy has also been seen but more data is needed, she noted.

Areas of unmet need

An area of unmet need that calls for more research is nonpenicillin drug allergy during pregnancy, according to Shah.

“There is a lack of published non-penicillin drug allergy evaluation protocols,” she said. “It’s very important to note that when patients come in for drug allergy evaluations that is not for penicillin and is not relevant during that time frame, sometimes delabeling during pregnancy might not be the best option.”

Avoiding evaluation in high-risk scenarios is important, Shah continued.

“Depending on what the medication is, their history with the medication and what the patient’s comorbidities are, it may not be the best time to do drug allergy evaluation because we don’t have as much literature for medications that are not penicillin,” she said.

Shah recommended to always ensure that all medications being considered for evaluation are safe for use during pregnancy.

Drug allergy evaluation during breastfeeding can be considered, according to Shah.

“It is important to ensure that the medication that’s in question is safe in breastfeeding and doesn’t interfere with milk supply,” Shah continued, adding that the NIH drugs and lactation database LactMed is a good resource for drug safety in lactation, and that ultimately, shared decision-making with the patient and allergist is important before proceeding with any testing.

Key considerations

There are negative consequences associated with a penicillin allergy label, according to Shah.

“Antimicrobial stewardship is a really important consideration,” she said. “We know that with having a penicillin allergy that there is an increased rate in use of broad-spectrum antibiotics, which can lead to resistant organisms. There’s also an association with increased morbidity and mortality, higher rates of hospital readmissions and surgical site infections. All of this combined can also lead to higher health care costs.”

Shah additionally noted that although 8% to 10% of pregnant patients report a penicillin allergy, more than 90% can safely tolerate penicillin when they come into the allergy clinic for evaluation.

“For patients that have a low-risk history for penicillin allergy, this may be a really nice population to consider doing further evaluation and testing in pregnancy,” she said.

Shah cited several studies that showed the efficacy of penicillin allergy delabeling using skin testing and oral challenges in pregnant patients. She also reviewed a few studies looking at direct ingestion challenges in pregnancy (evaluation without performing skin testing first).

“Overall, it looks like this may be an area where we need more literature but looks promising,” she said. “An additional important factor to consider in drug allergy testing and delabeling is whether obstetrician colleagues feel comfortable recommending drug allergy testing to their patients. The American College of Obstetricians and Gynecologists have their own practice parameters. What they have concluded is that penicillin allergy testing can be safe during pregnancy and can be beneficial for women who report a low-risk penicillin allergy. This shows that obstetricians are ready and willing to recommend penicillin allergy testing.”

Novel protocols

Shah then went on to describe novel protocols for drug allergy testing.

“At the Cleveland Clinic, we in the last year or so have developed a new consult order in our [electronic medical record],” she said. “Essentially there’s an order that’s called penicillin allergy consult that can be placed by any provider in the Cleveland Clinic system for anyone that has a penicillin allergy.”

She explained that patients can self-schedule through MyChart for an in-person or virtual visit. If a pregnant patient is seen virtually, an allergist will help schedule them for an in-person evaluation during their third trimester. The patient then undergoes a penicillin allergy evaluation through skin prick and intradermal testing with penicillin G, Pre-Pen [benzylpenicilloyl polylysine, ALK-Abelló] and ampicillin, and if negative, will proceed to a two-step oral challenge with amoxicillin.

Another approach, utilized by Massachusetts General Hospital, includes an e-consult to triage patients using history documented by an OB nurse. The patient is then scheduled to see an allergist when they are more than 30 weeks pregnant. Their method of testing is skin testing with penicillin, Pre-Pen and amoxicillin. If skin testing is negative, the patient proceeds to a one step oral challenge with amoxicillin.

Review of the Massachusetts General Hospital approach has shown that “patients who underwent allergy immunology evaluation had reduced rates of using peripartum vancomycin, clindamycin and gentamicin and increased rates of appropriately using penicillin and also increased use of appropriate first line antibiotic prophylaxis for GBS and [cesarean sections],” Shah said. “Performing drug allergy evaluations in pregnant patients in the third trimester is considered safe and feasible, depending on the patient’s history. We need more data for first and second trimester evaluation, for direct oral challenges, and evaluation of nonpenicillin antibiotic allergy evaluation in pregnancy, but risk stratification and shared decision-making are key.”

References:

• Blumenthal KG, et al. JAMA. 2020;doi:10.1001/jama.2019.19809.
• Carra S, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2021.07.046.
• Desai SH, et al. Perm J. 2017;doi:10.7812/TPP/16-080.
• Mak R, et al. J Allergy Clin Immunol Pract. 2022;doi:10.1016/j.jaip.2022.03.025.
• Wolfson AR, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2020.10.063.