(1245) Hypersensitivity Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

Objectives: Antibiotics are used to treat or prevent many types of bacterial infections. These drugs work by killing bacteria or preventing them from reproducing and spreading. Antibiotic use can result in a variety of adverse drug events which may range from mild to severe reactions. These events impact drug selection and encourage a patient-specific approach in prescribing to minimize harm. Of the adverse drug events associated with antibiotics, hypersensitivity reactions are very concerning. Drug hypersensitivity reactions occur when the body produces inappropriate immunologic or inflammatory responses to a medication, resulting in symptoms such as rash, anaphylaxis, or serum sickness. Patients with drug hypersensitivities should be educated on avoiding the medication and charts must appropriately document the reaction. Some antibiotics are known to be associated with hypersensitivity, but no study has systemically compared hypersensitivity associations for many available antibiotics. The objective of this study was to evaluate the association between hypersensitivity and antibiotics using the FDA Adverse Event Reporting System (FAERS).

Methods: FAERS reports from January 1, 2004, to December 31, 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify hypersensitivity cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (95% CI) for the association between antibiotics and hypersensitivity were calculated. ROR was calculated as the ratio of the odds of reporting hypersensitivity versus all other events for a given drug compared with this reporting odds for all other drugs present in FAERS. An association was considered to be statistically significant when the lower limit of the 95% CI was greater than 1.0.

Results: A total of 16,009,712 reports (including 144,714 hypersensitivity reports) were considered, after inclusion criteria were applied. 72 antibiotics were evaluated, and 39 of those antibiotics were significantly associated with hypersensitivity. The top 10 antibiotics with the highest number of hypersensitivity reports were trimethoprim-sulfamethoxazole (2,550), amoxicillin (1,483), ciprofloxacin (1,327), moxifloxacin (1,253), levofloxacin (1,170), azithromycin (1,039), amoxicillin-clavulanate (1,012), doxycycline (840), metronidazole (822), and clarithromycin (776). The top 10 antibiotics with the highest hypersensitivity ROR (95% CI) were penicillin G 8.17 (7.45-8.96), dalbavancin 6.78 (5.00-9.19), cefaclor 5.38 (4.40-6.57), moxifloxacin 4.62 (4.36-4.89), oritavancin 4.14 (2.89-5.92), penicillin V 3.79 (3.35-4.30), ceftibuten 3.62 (2.04-6.44), bacitracin 3.43 (2.88-4.10), cefprozil 3.35 (2.37-4.74), and erythromycin 3.22 (2.94-3.51).

Conclusions: Out of the 72 antibiotics evaluated in the FAERS database, 39 were significantly associated with hypersensitivity. Trimethoprim-sulfamethoxazole had the highest reported number of hypersensitivity reactions followed by amoxicillin, ciprofloxacin, moxifloxacin, levofloxacin, azithromycin, amoxicillin-clavulanate, doxycycline, metronidazole, and clarithromycin. Penicillin G had the highest ROR with hypersensitivity followed by dalbavancin, cefaclor, moxifloxacin, oritavancin, penicillin V, ceftibuten, bacitracin, cefprozil, and erythromycin.