Effects of Sex and Gender in Immediate β-Lactam Antibiotic Allergy: A Systematic Review and Meta-Analysis

Background: β-Lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of β-lactam antibiotics.

Objective: This systematic review and meta-analysis aimed to identify sex- and gender-based differences in the prevalence of immediate β-lactam allergy.

Methods: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013 and 2023. Patients with a documented β-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in β-lactam allergy with meta-analysis.

Results: We included 69 primary studies assessing 53,989 participants from outpatient and inpatient cohorts. A total of 7,558 patients had a confirmed β-lactam allergy. There was no difference in the prevalence of positive β-lactam allergy test between males and females. Subgroup analysis of studies that performed oral challenges showed a higher risk of β-lactam allergy in females compared with males (relative risk = 1.40; 95% CI, 1.18-1.66; P < .001; I² = 77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in β-lactam allergy studies.

Conclusions: Our findings suggest both sex-based and gender-based differences in the prevalence of immediate β-lactam allergy. Biological factors such as sex hormones and gender-based behaviors including increased health care use may contribute to higher rates of β-lactam allergy diagnosis in females.