PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis

PET/CT imaging in humans with TB correlates with drug response and final treatment outcomes. Visualizing Drug Responses in TB A pair of papers by Chen et al. and Coleman et al. investigate how changes in quantitative positron emission tomography/computed tomography (PET/CT) scans in both nonhuman primates and humans can be used as early surrogate markers of treatment efficacy in tuberculosis. The Coleman et al. study shows that treatment of Mtb-infected macaques with linezolid and the second-generation oxazolidinone AZD5847 resulted in a reduced bacterial load at necropsy and reduced FDG PET avidity and CT-quantified lung pathology. Similar PET/CT changes were seen in human patients infected with extensively drug-resistant Mtb and treated with linezolid. The companion study by Chen et al. corroborated this effect in a prospective analysis of patients with multidrug-resistant tuberculosis and demonstrated that early PET/CT changes predicted final treatment outcomes. Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[18F]-fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.