Antibiotics are the Most Common Drugs to Induce Anaphylaxis

A study revealed antibiotics, particularly ceftriaxone, were the most common drugs to lead to anaphylaxis in children.1

“Non-steroidal anti-inflammatory drugs, particularly ibuprofen, constituted the second most frequently implicated drug group,” wrote investigators, led by Azize Pınar Metbulut, from the pediatric immunology and allergy department at Ankara Bilkent City Hospital in Turkey.

Anaphylaxis, a life-threatening reaction, can lead to symptoms of flushing, pruritus, hives, angioedema, shortness of breath, wheezing, nausea, vomiting, diarrhea, hypotension, oxygen desaturation, and cardiovascular collapse.2 Children and adults have different anaphylaxis presentations regarding symptoms and severity.

A systematic review reported a worldwide prevalence of anaphylaxis in the pediatric population ranging from 0.04% to 1.8%. Moreover, another study showed that 1 in 7 children with anaphylaxis experience a biphasic reaction after receiving an intramuscular injection of epinephrine.3

Another study showed in drug-induced anaphylaxis, skin manifestations were more common in children than in adults.2 With other symptoms, cyanosis was more present in children < 5 years, neurological symptoms were more present in school-age children, and hypotension was more present in adolescents. The frequency of gastrointestinal symptoms did not appear different between adults and children, nor was it confirmed whether cardiovascular symptoms, respiratory symptoms, and shock were less frequent in children than adults.

An Australian study on pediatric anaphylaxis found that nearly 50% of the diagnoses are missed.2

Going off previous studies, Metbulut and colleagues sought to determine demographic characteristics, risk factors, clinical presentations, causative agents, and management approaches regarding drug-related anaphylaxis in the pediatric population.1 They conducted a multicenter retrospective study with patients aged 1 month - 18 years (IQR 56.5–161.5 months; mean age: 107 months; 48.1% females) who met the standardized criteria for anaphylaxis and had a likely diagnosis of drug-induced anaphylaxis. Patients were admitted to 11 participating centers in Pediatric Allergy and Immunology outpatient clinics between January 2017 and December 2022.

The team identified 293 anaphylactic episodes among 265 patients, which occurred due to parenteral (59.7%) and peroral (40.3%) drug administration. Anaphylaxis was more common in the hospital setting (62.1%; n = 182) than in home environments (34.1%; n = 100).

The study found that the top suspected drugs related to anaphylaxis were antibiotics (56.7%), followed by non-steroidal anti-inflammatory drugs (NSAIDs) (25.7%) and chemotherapeutics (3.4%). The cephalosporin group, especially ceftriaxone, was the leading culprit of drug-related anaphylaxis among antibiotics. The most common NSAID that can lead to anaphylaxis is ibuprofen.

In total, 54.9% (n = 161) had moderate anaphylaxis and 39.6% (n = 116) had severe anaphylaxis. Among the 265 patients with anaphylaxis, only 5 experienced a biphasic reaction and 72% received adrenaline treatments. No patients died.

Clinicians performed 64 diagnostic tests, such as skin prick, intradermal, and drug provocation tests, between 1 month to 10 years after the index reaction to confirm drug-induced anaphylaxis. Positive results were discovered in 23.4% (n = 15) of participants on the skin prick test, 17.2% (n = 11) on the intradermal test and 20.3% (n = 12) on the drug provocation tests. Overall, 39 patients had confirmed drug-related anaphylaxis, and 4 patients underwent suspected drug desensitization protocols.

“We propose pediatric patients who experience drug-induced anaphylaxis should undergo evaluation at specialized centers, to ensure accurate diagnosis, to prevent recurrence and identify safe alternative treatments,” investigators wrote.

References

1. Metbulut AP, Haci İA, Can D, Bekiş Bozkurt H, Cavkaytar Ö, Arga M, Özçeker D, Kavas Yildiz Y, Vezir E, Arikoğlu T, Kuyucu S, Azkur D, Güvenir H, Kendirci N, Orhan F, Usta Güç B, Bahçeci S, Dibek Misirlioğlu E. Evaluation of drug-related anaphylaxis in children: multi-center study. Eur J Pediatr. 2025 Mar 7;184(3):230. doi: 10.1007/s00431-025-06068-x. PMID: 40053151.

2. Bianchi A, Valluzzi R, Crisafulli G, Bottau P, Caimmi S, Franceschini F, Liotti L, Mori F, Riscassi S, Saretta F, Scavone S, Caffarelli C. Drug-Induced Anaphylaxis in Children. Biomedicines. 2024 Feb 27;12(3):527. doi: 10.3390/biomedicines12030527. PMID: 38540140; PMCID: PMC10967707.

3. Derman, C. Biphasic Anaphylaxis in Children: Study Finds 1 in 7 Cases Occur After Epinephrine. HCPLive. February 12, 2025. https://www.hcplive.com/view/biphasic-anaphylaxis-in-children-study-finds-1-in-7-cases-occur-after-epinephrine. Accessed March 17, 2025.