Clarithromycin hypersensitivity in children: Is there a link with β-lactam hypersensitivity?

Clarithromycin hypersensitivity is reported as the most common cause of non-β-lactam antibiotic allergy in children. Clarithromycin is frequently prescribed in cases of suspected β-lactam hypersensitivity. Oral provocation tests stand as the gold standard to confirm drug hypersensitivity as diagnostic value of skin tests is variable. We analyzed the frequency of true clarithromycin hypersensitivity ratio and its relationship with β-lactam allergy among children with suspected clarithromycin hypersensitivity and evaluated the diagnostic value of skin tests.

The study included 160 children referred with suspected clarithromycin hypersensitivity. Clinical history and allergy workups including skin tests or/and oral provocation tests were retrieved from medical records.

Oral provocation test confirmed clarithromycin hypersensitivity rate was 5.6% (n = 9/160). Skin tests with clarithromycin showed positivity in 32.6% (n = 29/89) of the tested patients. The sensitivity of clarithromycin skin tests was negligible, and specificity was 73.9% (95% confidence interval [CI], 64.7-81.8). Eighty-eight of the patients (55%) reported that they had previously tolerated a β-lactam antibiotic. β-lactam hypersensitivity was suspected in 40% (n = 64/160) of the patients (simultaneous [n = 10], sequential [n = 19], distant form [n = 35]) in relation with clarithromycin usage. β-lactam hypersensitivity (95% CI, 2.1-70.6, p = .005) and sequential usage of clarithromycin after the development of a rash with amoxicillin-clavulanic acid (95% CI, 2.0-96.4, p = .007) were found as risk factors for confirmed clarithromycin hypersensitivity.

The frequency of confirmed clarithromycin hypersensitivity was found low among suspected patients. Oral provocation test is crucial for definite diagnosis. Confirmed β-lactam allergy may be attributed as a risk factor for clarithromycin hypersensitivity, particularly clarithromycin treatment after a developing rash with amoxicillin-clavulanic acid in sequential usage.