What is the significance of a positive Quantiferon (QuantiFERON-TB Gold) test result in Mycobacterium avium complex (MAC) infection?

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From the Guidelines

A positive QuantiFeron-TB Gold test in a patient with Mycobacterium avium complex (MAC) infection is likely a false positive result, and treatment should focus on the MAC infection rather than latent tuberculosis. The QuantiFeron test is designed to detect Mycobacterium tuberculosis infection, not MAC. However, cross-reactivity can occur because MAC and tuberculosis share some antigens. If you have a positive QuantiFeron test but clinical evidence points to MAC infection (through positive cultures from sputum, bronchial wash, or tissue samples), the following treatment approach is recommended:

  • Standard MAC treatment typically includes a macrolide (clarithromycin 500mg twice daily or azithromycin 500mg daily) 1
  • Ethambutol (15mg/kg daily) is often used in combination with a macrolide 1
  • Rifampin (600mg daily) may also be included in the treatment regimen 1
  • Treatment should continue for at least 12 months after culture conversion 1 For patients with MAC and a positive QuantiFeron test, consultation with an infectious disease specialist is recommended to determine if concurrent treatment for latent tuberculosis is necessary 1. This decision should be based on risk factors for TB exposure, radiographic findings, and clinical presentation 1. The distinction matters because MAC and tuberculosis require different treatment approaches, and unnecessary TB treatment carries risks of medication side effects. In terms of treatment outcomes, a study published in 2007 found that macrolide-containing regimens were effective in treating MAC lung disease, with sputum conversion rates of 84% in patients infected with susceptible strains 1. Another study found that the use of a four-drug clarithromycin-based regimen resulted in sputum conversion in 92% of patients who completed at least 6 months of therapy 1. Overall, the treatment of MAC infection should be guided by clinical evidence and expert consultation, rather than relying solely on the results of the QuantiFeron test 1.

From the Research

Quantiferon Positive in Mycobacterium Avium Complex

  • The QuantiFERON-TB GOLD In-Tube test is used to diagnose Mycobacterium avium complex (MAC) disease, but its positive response rate is relatively low 2.
  • A study found that only 11.3% of patients with MAC disease showed a positive response with QuantiFERON-TB GOLD In-Tube, and these patients were mostly elderly with a history of pulmonary tuberculosis 2.
  • Another study found that 7% of patients with pulmonary Mycobacterium avium complex disease had a positive QuantiFERON TB-2G test result 3.
  • The QuantiFERON TB-2G test has a mean sensitivity of 86% and a mean specificity of 94% in differentiating active tuberculosis from nontuberculous mycobacteriosis, including MAC disease 3.
  • However, the test may not provide certainty regarding cure of infection, as its results may be long-lasting after treatment and may not be resolved over time 3.

Diagnosis and Management of MAC Disease

  • MAC disease can be chronic, debilitating, and associated with high mortality, but its diagnosis is often delayed due to nonspecific presentation and radiological findings that overlap with other pulmonary diseases 4.
  • Diagnosis of MAC disease requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture, and treatment involves a 3-drug regimen including macrolide, rifamycin, and ethambutol 4.
  • Treatment outcomes for MAC disease are often suboptimal, with frequent drug-related side effects and refractory or recurrent disease 4.
  • Research priorities include developing new diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clinical reevaluation of the QuantiFERON TB-2G test as a diagnostic method for differentiating active tuberculosis from nontuberculous mycobacteriosis.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2006

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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