The Effect of Rifabutin in Mycobacterium Abscessus With Inducible Clarithromycin Resistance

The Effect of Rifabutin in Mycobacterium Abscessus With Inducible Clarithromycin Resistance: a Randomized Study

Background: Mycobacterium abscessus, one of the most common species of nontuberculous mycobacterium (NTM), poses a significant clinical challenge due to its natural resistance to antibiotics and high treatment failure rates, particularly in lung diseases. Among its subspecies, M. abscessus subspecies abscessus is especially prone to developing inducible resistance to Clarithromycin. This resistance mechanism is primarily due to the activation of the erm(41) gene,which inhibits Clarithromycin from effectively binding to the bacterial ribosome, diminishing its bactericidal efficacy. Rifabutin, an antibiotic widely used in treating tuberculosis and certain NTM infections, has been shown to inhibit the activation of the erm(41) gene by suppressing the whiB7 protein in M. abscessus, suggesting potential efficacy against inducible resistance. However,current evidence primarily stems from in vitro susceptibility studies and case reports, with a notable lack of systematic clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Mycobacterium Abscessus Lung Disease
• Intervention / Treatment: Drug: Rifabutin; Drug: No Rifabutin

Detailed Description

Specific Aims: The primary aim of this study is to evaluate the efficacy and safety of Rifabutin in treating M. abscessus lung disease with inducible Clarithromycin resistance. Specific objectives include:

• Assessing sputum culture conversion rates and clinical improvement when Rifabutin is added to the standard treatment regimen.
• Investigating the effect of Rifabutin on progression-free survival (PFS).
• Evaluating patient tolerance and adverse events throughout treatment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Yunlin County
    • Douliu, Yunlin County, Taiwan, 640
      • Recruiting
      • National Taiwan University Hospital Yunlin Branch
      • Contact: YI-LIN LEE, MD; Phone Number: +886972655633; Email: cycherlee@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged ≥ 18 years
• Diagnosis of pulmonary disease caused by Mycobacterium abscessus confirmed by clinical evaluation and laboratory results
• Antimicrobial susceptibility testing indicating inducible resistance to clarithromycin
• Clinically stable and suitable for antibiotic treatment
• Radiographic evidence of active pulmonary infection
• Willing and able to provide informed consent

Exclusion Criteria:

• Known hypersensitivity to rifabutin or intolerance to other study medications
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Standard Rifabutin dose group: Oral administration once daily, with dosage adjusted based on the patient's body weight and hepatic/renal function; typically 300 mg, combined with standard therapy.	Drug: Rifabutin; The treatment group (received standard treatment plus Rifabutin, with the dosage adjusted according to weight and renal function)
Experimental: Control Group; Standard therapy: Amikacin, Imipenem, Tigecycline, Linezolid, and Clarithromycin or Azithromycin.	Drug: No Rifabutin; the control group (received standard treatment only).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In the study period, we have screened 286 patients with kidney transplant and enrolled 50 participants who were KTR and had LTBI.	In the study period, we have screened 286 patients with kidney transplant and enrolled 50 participants who were KTR and had LTBI. Among them, 24 received 9H regimen, 10 had 3HR, one underwent 3HP, one used 4R, and the remaining 14 declined LTBI treatment. Finally, there were 36 patients received LTBI treatment. Regarding ADRs, there was no severe ADR, but 3 of 3HR group had mild (Grade 1) non-specific reaction of malaise, which was borderline higher than 9H group (25% vs 0%, p=0.025). The effect on FK506 by rifamycin was all adjustable except one using 3HP regimen. There was no kidney injury found. The dosage of FK506 needed to titrated up to around two-fold. Only one of 9H group had interrupted LTBI treatment course due to other cause. The incompletion rate was insignificant difference between 9H and 3HR groups (4% vs 0%, p=667). 3HR regimen cost less and patients had lower clinic return times compared with 9H group.	within 2years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Actual): March 1, 2026
• Study Completion (Estimated): June 18, 2026

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Rifabutin
• Other Study ID Numbers: 202411007MINA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No