Objective: Nitroimidazoles, particularly metronidazole and ornidazole, are widely used in the treatment of anaerobic and protozoal infections. Although generally well tolerated, hypersensitivity reactions (HSRs) to nitroimidazoles have been increasingly recognized and may significantly limit antimicrobial options. The diagnosis of HSRs is often challenging due to overlapping clinical presentations, concomitant drug exposures, and the limited sensitivity of available diagnostic tests. This study aimed to characterize the clinical features, diagnostic methods, and causality assessment outcomes in patients evaluated for suspected nitroimidazole hypersensitivity.

Materials and Methods: Among 1,570 patients tested for drug allergy between January 2019 and October 2025, 30 for whom diagnostic testing with nitroimidazoles was planned were included. Demographic data, clinical characteristics, and laboratory findings were systematically reviewed. Diagnostic procedures included skin prick testing (SPT), intradermal testing (IDT), and drug provocation testing (DPT). Causality was assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria and the Naranjo Adverse Drug Reaction Probability Scale.

Results: Of the 30 patients, 23 had a history consistent with nitroimidazole hypersensitivity. Most were middle-aged women (mean age 43.8 years, 82.6% female), and two-thirds had an atopic background. Immediate-type reactions predominated (87%), most commonly urticaria, angioedema, or both. Allergy testing was performed in 20 patients: all SPTs were negative, IDT was positive in one (4.3%), and DPT confirmed hypersensitivity in two (8.7%). Overall, two patients had confirmed metronidazole allergy and one had ornidazole allergy, whereas most were reclassified as non-allergic after testing. Causality assessments categorized the majority as unclassified (WHO-UMC, 69.6%) or possible (Naranjo, 65.2%).

Conclusion: Nitroimidazole hypersensitivity is rare but clinically important. Most reported allergies were unconfirmed upon systematic re-evaluation, underscoring the value of structured diagnostic algorithms. While causality tools aid interpretation, confirmatory DPT remains the cornerstone for accurate diagnosis and safe antimicrobial stewardship.