1360. Disseminated Mycobacterium abscessus Infections in Patients with Neutralizing Anti-interferon-gamma Autoantibodies Treated with Rifabutin-based Combination Regimens

Abstract

BackgroundThis prospective study aimed to describe the treatment and safety outcomes of rifabutin-based combinations which has been shown to be synergistic in vitro, for patients with refractory M. abscessus infections and neutralizing anti-IFNγ antibodies.MethodsPatients failing at least two standard macrolide-based regimens were recruited from hospitals across Taiwan since August 2017. They received rifabutin (RFB > 300 mg/day) initially with azithromycin (AZR 500 mg/day) and at least one parenteral agent and were monitored thereafter clinically on a monthly basis and by 3–6 monthly PET-CT imaging.ResultsOf 12 referred patients, only four had complete evaluations. The median age was 41 years and follow-up duration was 543 (range 307–668) days. All patients had lung and lymph node disease, two also had liver, bone and joint involvements and all were HLA-DR 16:02, HLA-DQ 05:02 positive. Prior to starting RFB–AZR, they had received at least four successive antimycobacterial regimens, but showed progression of existing lesions (2) or new lesions (2). Following RFB–AZR, all four patients experienced adverse reactions, including reactive dermatoses (2), fevers (2), leukopenia (2), thrombocytopenia (1), hearing loss (1), acute kidney injury (1), which necessitated withdrawal of rifabutin (4), short-term steroid use (2), and replacement of tenofovir with entecavir for chronic hepatitis B (1). All patients recovered fully from these adverse effects. Rifabutin was successfully restarted on first attempt (3) and on third attempt (1). The longest symptom-free interval on RFB–AZR was 331 days and the lowest maintenance dose was RFB 150–AZR 250 thrice weekly. Follow-up PET-CT confirmed good resolution of previous hot spots (mean SUVmax −4.5) except for the patient who did not tolerate RFB 300 due to fever and nausea on the first re-challenge, whose PET-CT detected a slight increase in mean SUVmax +0.6 and was hospitalized for dry cough on daily AZR–ciprofloxacin. The latter eventually tolerated a lower daily dose RFB 150–AZR 250 and became asymptomatic.ConclusionRifabutin is an oral agent that can be effectively combined with azithromycin in long-term maintenance regimens against M. abscessus in immunodeficient adults. Adverse effects are frequent early on; however, rechallenge appears to be safe and outcomes favorable. Disclosures All authors: No reported disclosures.