The Effect of Rifabutin in Mycobacterium Abscessus With Inducible Clarithromycin Resistance

Phase 4RecruitingNCT07514364

National Taiwan University Hospital60 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mycobacterium Abscessus Lung Disease

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: within 2years