Cimino, Christo

Abstract Background Mycobacterium abscessus complex (MABC) is a difficult-to-treat infection due to antibiotic resistance. Our study aimed to assess omadacycline’s (OMC) clinical and microbiological outcomes for the treatment of pulmonary MABC. Methods A retrospective study was carried out across 12 US medical institutions from 1/2018-4/2023 to examine the clinical outcomes, and tolerability of OMC treatment for pulmonary MABC. Patients aged ≥ 18 years who were treated with OMC for ≥ 3 months were included. The primary outcome was clinical success at 3, 6, and 12 months. The secondary outcomes were sputum culture conversion rate, adverse effects, and clinical success by subspecies and macrolide susceptibility. Results Thirty-five patients were included in this analysis. Most patients were female (74.3%) and Caucasian (74.3%), with a median (IQR) age of 61 years (51–70). Subspeciation was performed for 22 isolates with predominant M. abscessus subspecies (77.3%). Moreover, coinfection with other NTM species was present in 28.6% of cases where Mycobacterium avium complex was present in 8 cultures. Sixty-eight percent of the MABC isolates were confirmed to be macrolide resistance; half (12/24, 50.0%) were evident by the presence of functional erm gene, while the other half by antimicrobial susceptibility (Table 3). Of the remaining isolates, 14% were macrolide-susceptible, while no information was reported in 17%. The median (IQR) treatment duration of OMC was 8 months (3.9 – 15.7). The most commonly co-administered antibiotics were intravenous amikacin, imipenem/cilastatin, inhaled amikacin and clofazimine with the same percentage (42.9%) (Table 1). Overall, MABC clinical success was observed in 71.4%, 89.7%, and 90.9% in 3-, 6- and 12 months, respectively (Table 3). Adverse effects reported in 34.3%. The most common side effects were gastrointestinal intolerance (25.7%) and hepatoxicity (11.4%), which led to drug discontinuation in 22.9%. Conclusion OMC treatment showed clinical success in > 70% of patients with pulmonary MABC including patients with macrolide resistant strains for more than 3 months. However, larger studies are needed to validate the outcomes beyond 12 months. Disclosures Kaylee E. Caniff, PharmD, BCIDP, T2Biosystems: Honoraria Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker

Abstract Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2–5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug–drug interactions, and adverse drug reactions.

ABSTRACT Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49–67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo ( 4 – 14 ), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).