ArticleThe Journal of antimicrobial chemotherapy2026
Exposure to azithromycin and the effect of co-administration of rifampicin in patients with non-tuberculous mycobacterial disease.
Article in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesAzithromycin is a key drug in the treatment of most non-tuberculous mycobacterial (NTM) diseases. Its exposure may be decreased by rifampicin co-administration, but to what extent is largely unknown. We measured azithromycin exposure in an NTM disease patient population and quantified the effect of rifampicin co-administration.
methodsWe retrospectively collected plasma azithromycin area-under-the-curve from 0 to 6 hours after administration in mg/L*hours (AUC0-6h), peak (Cmax), and trough (Cmin) concentrations from the TDM service at Radboudumc, The Netherlands. Azithromycin exposure measures were compared between patients with and without concurrent rifampicin use, and within patients who had rifampicin stopped during treatment.
resultsWe analysed data of 130 patients, of whom 59% had NTM pulmonary disease. The azithromycin geometric mean of AUC0-6h in patients with (n = 48) and without (n = 82) rifampicin were 0.90 versus 1.83 mg/L*h, Cmax 0.22 versus 0.46 mg/L, and Cmin 0.043 versus 0.13 mg/L, respectively. A within-patient comparison in 14 subjects showed geometric means of AUC0-6h, Cmax, and Cmin (90%-CI) with rifampicin were 62% (45%-74%), 58% (38%-72%) and 66% (48%-77%) lower than without rifampicin. Interventions based on TDM enabled a strong increase in exposure to azithromycin. No association between azithromycin exposure and disease outcomes was shown, but the number of patients in these analyses was small.
conclusionsThis study provides new population exposure data for TDM of azithromycin in NTM disease. Rifampicin co-administration reduces azithromycin exposure by at least half, underscoring the need for upfront azithromycin dose adjustment, application of TDM, or considering alternative drugs for rifampicin, also considering controversy around its effectiveness and adverse effects.
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