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Your Good Health: Tough To Tell When Penicillin Is Causing Allergic Reaction

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Navigating Cephalosporin Prescribing In Patients Allergic To Penicillin

March 03, 2025

5 min read

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I routinely see prescribers avoid prescribing cephalosporin antibiotics for patients with a penicillin allergy.

One of the drivers of this is that our electronic health record systems often warn prescribers that there is a risk for cross-reactivity. Where does this warning come from, and how much risk is there of using cephalosporins in patients with a penicillin allergy?

Penicillin allergies are the most common drug allergy that patients report. Studies done within EHR systems have shown an incidence of 6% to 25%, depending upon the geographical region and patient population. Many penicillin allergies are self-reported and often not accurate. Multiple studies have shown more than 95% of patients reporting a penicillin allergy ultimately can tolerate penicillin antibiotics.

Most penicillin allergies occur during childhood, and unfortunately, these patients often carry this allergy label with them for decades. It is common for true IgE-mediated hypersensitivity to penicillin to wane over time, with approximately 80% of patients becoming tolerant to penicillin over 10 years. It is also common for patients to be labeled as penicillin allergic unnecessarily because of common side effects such as gastrointestinal intolerance, headaches, concomitant viral rashes and other benign symptoms. Although penicillin allergy testing is available, only a small fraction of patients with a penicillin allergy undergoes confirmatory testing.

A myth is born

Cephalosporin allergies are not uncommon, with approximately 2% of patients reporting an allergy. Cephalosporin allergies have largely been attributed to an antigenic response to the R1 or R2 side chains rather than the core beta-lactam portion of the molecule. Aminopenicillins such as ampicillin and amoxicillin do share a common R1 side chain with the first-generation oral cephalosporins cefuroxime and cephalexin, so patients with a confirmed allergy to those may have a higher risk of cross-reactivity. However, cefazolin, which is used widely in hospitalized patients and for surgical prophylaxis, has a unique R1 side chain and is not like penicillin, so the risk of cross-reactivity is extremely low. This is important because the use of alternative perioperative antibiotics for surgical prophylaxis has been shown to result in higher rates of surgical site infection.

The avoidance of cephalosporins in patients with a penicillin allergy dates to the 1960s and concerns of increased reactions. In the 1970s, there were anecdotal reports of increased reactions when using cephalosporins in patients with penicillin allergy, but these were small selective case series. In the mid- and late 1970s, other papers also suggested avoiding cephalosporins in patients with a penicillin allergy because some patients appeared to have an increased incidence of allergic reactions to cephalosporins, despite any clear evidence that these allergies were due to cross-reactivity vs. A new independently acquired allergy. These papers stated patients with a penicillin allergy could also have an increased rate of reactivity to immunologically unrelated drugs. From this, the practice of avoiding cephalosporins in patients with a penicillin allergy became common.

The myth that 10% of patients with a penicillin allergy will have cross-reactivity to cephalosporins was also born despite the lack of supporting data.

Removing EHR warnings

As previously stated, the EHR warning when prescribing a cephalosporin in a patient with a penicillin allergy can prompt prescribers to use a non-beta-lactam antibiotic. What happens to prescribing practices if this warning is removed?

A retrospective study by Macy and colleagues examined the removal of the warning. Their results showed that removal was associated with a change in dispensing or administration of a cephalosporin antibiotic. This study was carried out in the Kaiser Permanente Southern California and Northern California health systems. The Kaiser Southern California site was the intervention site, whereas the Northern California site was the comparison site that did not remove the warning.

There were more than 10 million antibiotic courses in the analysis, with over half occurring after removal of the alert. Most of the courses of antibiotics were oral, with 18% being parenteral courses. The researchers found that cephalosporin use increased from 17.9% to 27% among patients with a penicillin allergy after removal of the alert. The administration or dispensing of cephalosporins increased by 47% among patients with penicillin allergy at the intervention site compared with those in other groups. Additionally, use of other antibiotics decreased: clindamycin from 13.7% to 11.4%, and fluoroquinolones from 12.8% to 10.5%. First-generation cephalosporins were used the most (71.7%), followed by third-generation agents (22.3%). Importantly, there was not a significant difference in antibiotic-associated adverse reactions or serious cephalosporin-associated morbidities before or after removal of the warnings.

When evaluating whether to start a cephalosporin in a patient with a penicillin allergy, the following approach is suggested by the current drug allergy guidelines. Stratifying patients based on anaphylactic vs. Nonanaphylactic histories as well as verified vs. Nonverified or unconfirmed penicillin allergies is recommended. Patients with a history of an unverified nonanaphylactic penicillin allergy may be administered any cephalosporin without allergy testing or additional precautions. In the rare circumstance of a patient with a history of anaphylaxis to penicillin, a non-cross-reactive cephalosporin, such as cefazolin, can be administered routinely without prior testing. Several charts have been published that can help practitioners choose antibiotics based on similarities of their side chains to minimize the risks of cross-reactivity.

Safe for most patients

Many clinicians will cite the risk of litigation as a reason to avoid prescribing cephalosporins in patients with a penicillin allergy. In 2018, a systematic review evaluated the medical malpractice and negligence cases when a cephalosporin or a carbapenem was prescribed for a patient with a penicillin allergy. The authors concluded that, although there was an increase in cases over the past 2 decades, overall, there was little legal risk when prescribing these agents to patients with a penicillin allergy.

In clinical practice, it is essential to evaluate each patient's allergy history. Penicillin allergies have been associated with increased health care costs, increased risks for drug-resistant infections, longer hospital stays and Clostridium difficile infections. Patient-reported allergies can be unreliable, so a thorough history should be obtained before prescribing. Allergic reactions with penicillin and cephalosporins can cause a range of allergic reactions. Although many allergic reactions are often overstated, it is important to differentiate mild to moderate reactions from more serious reactions. Penicillin allergy testing or referral to allergy professionals is important to identify which patients have true allergies and which do not. However, most patients with a penicillin allergy can safely be prescribed a cephalosporin.

References: For more information:

Jeff Brock, PharmD, MBA, BCIDP, is a HealioInfectious Disease News Editorial Board Member and infectious disease pharmacy specialist at MercyOne Medical Center in Des Moines, Iowa. He can be reached at jeff.Brock@mercyoneiowa.Org.

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Penicillin Allergy Consultation Via Telehealth Has 'poor Return Rate' In Pregnant Women

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Women's Allergy/Asthma Health

March 06, 2025

3 min read

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Key takeaways:

Out of 189 pregnant women, 22.7% opted for a telehealth vs. In-person penicillin allergy consultation.

Among those who chose the telehealth option, penicillin allergy was delabeled for 46.5% of patients.

SAN DIEGO — Nearly half of pregnant women who completed a telehealth penicillin allergy consultation did not go on to complete in-person allergy testing, according to a poster presented here.

The findings, presented at the 2025 American Academy of Allergy, Asthma and Immunology/World Allergy Organization Joint Congress, indicate a need for further research to examine the "poor return rate for further testing," researchers concluded.

Assessing consultation uptake

"Pregnant patients benefit hugely from having their penicillin allergy evaluated and often removed from their medical record," Margaret M. Kuder, MD, MPH, staff physician in allergy and clinical immunology at Cleveland Clinic, told Healio. "New [electronic medical record] technology makes this more accessible."

Researchers assessed 213 pregnant women with a scheduled penicillin allergy consultation between August 2023 and February 2024 to determine how presenting the patient with both a self-scheduling and telehealth option impacts consultation uptake.

"We anticipated that many people would utilize self-scheduling and telehealth," Kuder said.

Notably, researchers also explored how antibiotic use during labor and delivery differed between patients with a delabeled antibiotic allergy vs. Patients where this type of allergy was not delabeled.

Self-scheduling, telehealth outcomes

Within the study population, 189 patients (age, 31.63 years; 87% white) fulfilled the penicillin allergy consultation with an allergy provider, whereas the remaining 24 patients (age, 31.16 years; 87.5% white) did not fulfill the consultation.

When examining the use of self-scheduling among those who fulfilled the consultation, researchers found that a larger proportion of these patients did self-schedule their appointment rather than not use this option (n = 127; 67% vs. N = 62; 33%).

For telehealth usage, more patients who fulfilled their consultation opted for the initial in-person option vs. The initial telehealth option (n = 146; 77.3% vs. N = 43; 22.7%), according to the poster.

In the initial in-person consultation group, most patients (92%; n = 134) completed allergy testing (skin testing and/or an oral challenge), leaving only 8% (n = 12) of patients that did not complete testing. In contrast, researchers reported that 53.5% (n = 23) of the initial telehealth consultation group attended allergy testing whereas the remaining 46.5% (n = 20) of these patients did not come back. Kuder told Healio this finding was surprising.

"We need to investigate this further and figure out if there is some sort of disconnect in scheduling or communication preventing the completion of the drug allergy evaluation," Kuder said.

Among those who chose the initial telehealth consultation option, penicillin allergy was delabeled for 46.5% (n = 20) of patients, whereas this allergy was not delabeled for 53.5% (n = 23) of patients, according to the poster.

"Over half of the individuals who completed an initial telehealth evaluation did not have their penicillin allergy delabeled, many of these because they did not return for testing," Kuder said. "Some of [the not delabeled instances] were due to never returning for the in-person visit, and some were because they only did skin testing — not oral challenge— or one person had positive testing."

Labor and delivery data

Researchers additionally examined data for 185 patients for whom they had access to labor and delivery information and identified more patients with a delabeled vs. Not delabeled antibiotic allergy (110 patients vs. 75 patients).

"Most pregnant patients in our study who completed testing had negative results and had their penicillin allergy removed from the chart," Kuder told Healio.

According to the poster, a greater proportion of patients in the delabeled group used vs. Did not use an antibiotic during labor and delivery (68% vs. 32%). This pattern differed in the group of patients not delabeled for antibiotic allergy, as slightly fewer patients did vs. Did not use an antibiotic during this time (48% vs. 52%).

The most used antibiotic in both groups was cefazolin (n = 40 delabeled; n = 20 not delabeled). The poster further noted that penicillin G was the second most used antibiotic by patients in the delabeled group (n = 31), followed by non-beta lactam antibiotic (n = 3) and "other beta lactam" (n = 1).

In the not delabeled group, non-beta lactam antibiotic was the second most used antibiotic (n = 15), followed by penicillin G (n = 1). Researchers observed no use of "other beta lactam" in this group.

Moreover, researchers observed a significantly higher proportion of patients not delabled with a sub-optimal antibiotic used vs. Those with a delabled antibiotic allergy (21.3% vs. 2.7%; P < .001).

"[Delabeled] patients were more likely to receive a first-line antibiotic during the labor and delivery period," Kuder told Healio. "Future research will hopefully allow telehealth to be a more effective option as an initial evaluation for patients. Any pregnant patient with a listed penicillin allergy would benefit from an allergy evaluation."

For more information:

Margaret M. Kuder, MD, MPH, can be reached at kuderm@ccf.Org.

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