Azithromycin concentrations in CNS

Fråga: Are azithromycin concentrations in the central nervous system (CNS) adequate for treatment of infections in this location?

The query concerns a patient under treatment for a cerebellar lesion and meningitis, culture positive for Mycobacterium avium.

Sammanfattning: The information on azithromycin CNS penetration is scarce, but indicates good intracellular penetration. Due to the severity of the infection we recommend a slightly higher dosage than usual for treatment of MAC.

Svar: Azithromycin is registered for treatment of intracellular Mycobacterium avium complex (MAC) infections. According to the SPC azithromycin crosses the blood brain barrier to a small extent (1). Through literature searches we have found only one study concerning azithromycin and its penetration into the CNS. The study describes 20 patients who underwent elective surgery for brain tumors. The patients were given a single dose of 500mg azithromycin. This resulted in good brain tumor tissue concentrations of azithromycin 24 to 96 hours post-dose (3.64 +/- 3.81 to 0.74 +/-0.37 ug/g), while the concentration in CSF ranged from undetectable to 0.015 ug/ml (2). This difference is probably due to the highly lipophilic property of azithromycin. It should, however, be noted that the uptake of drug in tumor tissue might be higher than in normal tissue. On the other hand, azithromycin is concentrated intracellularly and has been measured at concentrations up to 50 times higher in various tissues (e.g. lung, tonsil, prostate) compared to concentrations in plasma (1).

Normal treatment dosage for azithromycin is 500 mg on day one, and 250 mg daily thereafter. 1200 mg is given once weekly for prophylaxis against MAC to HIV patients. However, there are no guidelines for long-term treatment of MAC. Due to the severity of the infection we recommend a slightly higher dosage than usual for treatment of MAC, i.e. a dose of 500 mg/day, which can be reduced to 250-300 mg/day upon clinical effect. Fass (cited 2013-06-11) Jaruratanasirikul S, Hortiwakul R, Tantisarasart T, Phuenpathom N, Tussanasunthornwong S. Distribution of azithromycin into brain tissue, cerebrospinal fluid, and aqueous humor of the eye. Antimicrob Agents Chemother 1996;40(3):825-826