Have hearing disorders been observed in relation to newer macrolides, eg clarithromycin and azithro

Fråga: Have hearing disorders been observed in relation to newer macrolides, eg clarithromycin and azithromycin, as is the case for erythromycin?

Sammanfattning: It is suggested that patients receiving azithromycin on a long-term basis should be monitored for new hearing problems.

Clarithromycin seems to have the potential to cause reversible hearing disorders and it may be important to notice any hearing problems related to treatment with the new generation of macrolides.

Svar: There are no cases reported of hearing disorders in low dosage treatment with either clarithromycin (250-500 mg x2) (1) or azithromycin (2) but there are several cases described after high dosage (2 gram per day) and for long-term treatment at low dosages (500 mg per day).

Thirteen patients with AIDS were, in a study, treated with two gram azithromycin per day against Mycobacterium avium. Clinical hearing loss, confirmed by audiometrical testing, was detected in two of these patients. One of them had concomitant severe liver enzyme abnormalities, and clarithromycin treatment was stopped, and the other one withdrew voluntarily from clarithromycin therapy (3).

In a controlled double-blind placebo-controlled crossover study including 15 patients with AIDS, receiving clarithromycin one gram x2 against M avium, 11 of them had at least one audiogram which showed three cases of a mild decrease in hearing ability. One had hypacusis before treatment was started,in one it developed during placebo treatment and in one it developed during clarithromycin treatment. No follow-up was performed (4).

In another study including 21 patients with AIDS, they were treated with 500 mg azithromycin per day against M avium for approximately one year. Hearing loss developed in three patients 30-90 days after beginning of therapy. In two of these cases the hearing deficit markedly interfered with normal conversation before azithromycin was discontinued. These impairments were rated as moderately severe by an audiologist. Follow-up audiometrical testing was normal on all three patients. However, one patient was rechallenged with azithromycin and within 14 days he noted a decline in his auditory acuity. When he stopped azithromycin he noted a return to normal hearing over 10-15 days. It is suggested that patients receiving azithromycin on a long-term basis should be monitored for new hearing problems (5).

The mechanism of ototoxicity of macrolides is not identified. 1 Personal communication with and letter from the Abbot Scandinavia AB, Ola Jeppson 2 Personal communication with Pfizer, Leif Eriksson 3 Fernandez-Martin J, Leport C, Morlat P, Meyohas M-C, Chauvin J-P, Vilde J-L: Pyrimethamine-Clarithromycin combination for therapy of acute toxoplasma encephalitis in patients with AIDS. Antimicrob Agents Chemother 1991; 35: 2049-2052 4 Dautzenberg B, Truffot C, Legris S, Meyohas M-C, Berlie HC, Mercat A, Chevret S, Grosset J: Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. Am Rev Respir Dis 1991; 144: 564-569 5 Wallace MR, Miller LK, Nguyen M-T, Shields AR: Ototoxicity with azithromycin. Lancet 1994; 343: 241