The true frequency and severity of myasthenia gravis (MG) exacerbation associated with the usage of fluoroquinolone and macrolide antibiotics remain unknown. We aimed to investigate the association between ciprofloxacin, levofloxacin, azithromycin, and MG exacerbation.

A retrospective review was performed on MG patients seen at a single institution between 2002 and 2022, who received ciprofloxacin, levofloxacin, or azithromycin. Amoxicillin usage was chosen for comparison. The strength of association between antibiotic usage and MG exacerbation was scored using the Adverse Drug Reactions Probability Scale. A mixed-effects logistic regression model was constructed to evaluate predictors of antibiotic-associated MG exacerbation (AAMGE).

365 patients had a total of 918 episodes of antibiotic usage (n = 339 for ciprofloxacin, n = 187 for levofloxacin, n = 392 for azithromycin). Frequencies of MG exacerbation following antibiotic use were: 8 (2.4%) for ciprofloxacin, 3 (1.6%) for levofloxacin, 6 (1.5%) for azithromycin, and 17 (1.9%) for all. Six patients had impending crisis/crisis, and 9 required rescue therapy. MG exacerbation was associated with MG-related hospitalization or ED visit in the preceding 6 months (p = 0.012), female sex (p = 0.023) and diabetes (p = 0.032). Infection was the most common confounder in exacerbations (88.2%). MG exacerbation was seen in 8/603 (1.3%) episodes of amoxicillin use, without a significant difference in frequencies of AAMGE among the four antibiotics (p = 0.68).

Usage of ciprofloxacin, levofloxacin, or azithromycin was associated with MG exacerbation in less than 2.5% of episodes of antibiotic use. Underlying infection may play a role in AAMGE. As AAMGE can be severe, decision-making regarding the use of these antibiotics should be individualized.