Study Review of Omadacycline for Mycobacterium Abscessus Pulmonary Disease

Review of Omadacycline

The widely known antibiotic tetracycline was first introduced in 1953 and is the most commonly clinically utilized first-generation tetracycline.¹ The second generation tetracyclines, doxycycline and minocycline, were approved in 1967 and 1971 respectively and are available both orally and intravenously.¹ Over time, resistance developed to the tetracyclines, and third generation agents were developed to combat this threat.² Tigecycline was developed in 2006 in an effort to overcome resistance mechanisms to tetracyclines, however it is not available orally due to low bioavailability and is often bot utilized due to a black box warning of increased mortality.²

Omadacycline was developed as an oral third generation tetracycline shortly after intravenous eravacycline in 2018.¹ Omadacycline is a semisynthetic tetracycline derivative with the same mechanism of action as other tetracyclines, however it is able to overcome common tetracycline resistance mechanisms with modifications at the C-7 and C-9 sections of the tetracycline D-Ring.³ It is available both orally and intravenously with 35% oral bioavailability.¹ Unlike other oral tetracyclines, patients must fast for 4 hours before taking and 2 hours after taking oral omadacycline, with no dairy, antacids or multivitamins for 4 hours after taking.⁴ Like other tetracyclines, it should also be spaced with aluminum, calcium, magnesium and iron containing products as absorption may be reduced.⁴

It exhibits a broader spectrum of in vitro activity against gram-positive aerobes, gram-negative aerobes, anaerobes and atypical bacteria when compared to older generation tetracyclines, including Methicillin Resistant Staphylococcus Aureus (MRSA), Vancomycin Susceptible and Resistant Enterococcus species (ex: VRE), Streptococcus pneumoniae, beta-hemolytic streptococci, Enterobacteriaceae, Haemophilus influenzae and Moraxella catarrhalis.⁵

Unlike other tetracyclines, omadacycline requires a loading dose, however it provides convenient once daily dosing.⁴ Intravenous dosing is typically 200mg once, followed by 100mg daily.⁴ Recommend oral dosing is 450mg orally once, followed by 300mg once daily.⁴ There are no recommended dose adjustments for kidney and liver impairment.⁴ Along with other tetracyclines, omadacycline can cause gastrointestinal side effects, which include nausea, vomiting, diarrhea and abdominal discomfort.^1,4 They are also associated with photosensitivity, and can impact tooth development when used in the pediatric population.^1,4 Patients should also be monitored for hepatotoxicity and anaphylactic reactions.^1,4

Omadacycline for Mycobacterium abscessus Pulmonary Disease

Mycobacterium abscessus (M abscessus) is a nontuberculous mycobacterial (NTM) species that causes pulmonary disease frequently associated with bronchiectasis, which is often resistant to most antibiotics.⁶ Treatment of M abscessus lung infections is often difficult as there are no drug regimens with established or predictable efficacy and it is typically resistant to most antibiotics.^6,7

Drug regimens are often lengthy, extensive and require intravenous treatment and long-term treatment often demonstrates challenges with many drug toxicities.^6,8 Oral macrolides are often recommend in treatment regimens, however most strains of M abscessus are intrinsically resistant, limiting oral treatment options.⁶ A well-tolerated oral treatment option with good penetration into lung tissue is essential to limit drug toxicities and ease treatment for patients with M abscessus lung infections.⁶ Favorable treatment results have been demonstrated utilizing oral omadacycline.⁶ Omadacycline is an aminomethylcycline antibiotic in the tetracycline class approved by the FDA in 2018 for treatment of ABSSSI and CABP.^4,6 It has shown good penetration into lung tissue, with previous retrospective studies presenting favorable results in NTM pulmonary disease caused by M abscessus.⁶ Additionally, Omadacycline has demonstrated in vitro activity against M abscessus as well as intracellular activity against M Abscessus within macrophages.⁶

In a randomized, double-blind, placebo-controlled, multicenter phase 2 study, omadacycline monotherapy demonstrated favorable results over placebo when treating adults with nontuberculosis mycobacterial pulmonary disease (NTM-PD) caused by M abscessus.⁶ This study was the first placebo-controlled trial to evaluate omadacycline monotherapy compared with placebo to treat M abscessus pulmonary disease.⁸

In this study, 66 adults were randomized to receive omadacycline 300 mg orally daily or placebo for 84 days.⁶ The primary efficacy endpoint was clinical response at day 84, defined as improvement in severity of at least half of symptoms present at day 1 (Definition 1) and improvement in severity of at least half of symptoms present at day 1 plus no deterioration in severity of any symptoms present at day 1 (Definition 2).⁶ The most frequently reported baseline symptoms included cough, fatigue, mucus production, shortness of breath and throat clearing.⁶ For the primary endpoint, 34.1% of omadacycline patients and 20.0% of patients treated with placebo were responders by Definition 1 and 34.1% and 12.0%, respectively, were responders by Definition 2.⁶ Important secondary and exploratory clinical and microbiological endpoints also favored omadacycline compared with placebo.⁶ The most frequent adverse effects with omadacycline treatment were gastrointestinal related, with nausea predominating.⁶

While the study was not powered to deliver conclusive efficacy assumptions and many of the assessment tools utilized were not validated, omadacycline treatment offered higher clinical response rates, improvement in outcomes and more favorable microbiologic endpoints compared to placebo.⁸ This trial was the first conducted with promising results to support oral monotherapy for M abscessus pulmonary disease.⁸ As certain limitations of this study exist and cannot be generalized to the entire population of patients with M abscessus pulmonary disease, the results suggested monotherapy with omadacycline can produce quantifiable and substantial clinical and microbiological results, identified by negative sputum cultures, in M abscessus pulmonary disease.⁸ Further studies are necessary to determine the ideal duration of therapy and the necessity of additional medications for optimal treatment.⁶

References

1. Pearson JC, Gillett E, Gadri ND, Dionne B. Tetracyclines, the old and the new: A Narrative Review. CMI Communications. 2025 (2)1:https://doi.org/10.1016/j.cmicom.2025.105059

2. Gallagher JC. Omadacycline: A Modernized Tetracycline. Clin Infect Dis.; 69(Suppl 1): S1-S5. doi: 10.1093/cid/ciz394

3. Karlowsky JA, Steenbergen J, Zhanel GG. Microbiology and Preclinical Review of Omadacycline. Clinical Infectious Diseases. 2019; 69 (S1): S6-15. DOI: 10.1093/cid/ciz395

4. Nuzyra [package insert]. Boston, MA: Paratek Pharmaceuticals; 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209816_209817lbl.pdf

5. Burgos RM, Rodvold KA. Omadacycline: a novel aminomethylcycline. Infection and Drug Resistance. 2019; 1895-1915, DOI: 10.2147/IDR.S171352

6. Winthrop KL, Flume PA, Khare R, et al. Omadacycline Monotherapy in Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium abscessus: Results from a Phase 2, Double-Blind, Randomized, Placebo-controlled Study. Clinical Infectious Diseases. 2026; ciag062, https://doi.org/10.1093/cid/ciag062

7. Daley CL, Iaccarino JM, Lange C, et al. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. Clin Infect Dis. 2020;71(4): e1-e36. doi: 10.1093/cid/ciaa241

8. Marino A, Marras TK. A Framework for Progress: What a Phase 2 Trial Teaches Us About Mycobacterium abscessus Research, Clinical Infectious Diseases, 2026; ciag063, https://doi.org/10.1093/cid/ciag063