1399. Clarithromycin–Rifampin-based Treatment for Non-tuberculous Mycobacterial Infections in Immunocompromised Patients Who Require Concomitant CYP-Metabolized Medications

Abstract

BackgroundNon-tuberculous mycobacteria (NTM) are causes of pulmonary and extrapulmonary disease that frequently affect immunocompromised hosts (ICH). Current treatment guidelines recommend a macrolide-based, multi-drug regimen that includes rifampin. Rifampin is a potent cytochrome P450 (CYP) 3A inducer, which often results in drug-drug interactions in ICH receiving multiple CYP substrates. One way to mitigate rifampin’s CYP induction is to utilize clarithromycin, a CYP inhibitor, as the accompanying macrolide. We evaluated the incidence of NTM treatment-related adverse events (AEs) in patients who received a clarithromycin-based regimen compared to patients who received an azithromycin-based regimen.MethodsWe conducted a retrospective review of NTM infection in 30 immunocompromised adults. All participants had a positive culture for a NTM and had received a rifamycin (rifampin or rifabutin) with a macrolide (azithromycin or clarithromycin) for treatment at Brigham and Women’s Hospital between 01/01/2011-10/18/2020 or Dana-Farber Cancer Institute between 06/03/2015-07/01/2020. The primary outcome was the incidence of NTM treatment-related AEs in patients who received a clarithromycin-based regimen compared to those who received an azithromycin-based regimen.ResultsThere were no significant differences in the reasons for discontinuation of NTM treatment or 90-day mortality between groups. The number of AEs possibly related to NTM treatment were similar in patients who received a clarithromycin-based regimen and those who received an azithromycin-based one (10/13 vs. 14/17; p=0.73). The most common AE was liver function test abnormalities (Table 1). Additionally, the proportion of patients requiring dose adjustments for interacting medications and patients with out-of-range tacrolimus levels were similar between the two groups (23.1% vs. 29.4%; p=0.76 and 8.0% vs. 6.0%; p=1.00, respectively). Table 1: Adverse events ConclusionA clarithromycin-based regimen for NTM treatment was safe and well tolerated in our patient population. This combination provides a good alternative for patients requiring medications that are CYP substrates, or those who cannot tolerate azithromycin.Disclosures Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member)