PET Scans May Optimise Tuberculosis
Medikoe Wellness Expert
80 feet road indira nagar, Bengaluru Aug 5, 2021
Shortening tuberculosis (TB) treatment by optimising antibiotic dosing might be possible using data obtained from PET/CT scans. In a first-in-human study, scientists favourably measured antibiotic concentration-time profiles in patients suffering from pulmonary TB, a crucial first step towards using PET scans as a tool to optimise TB treatment.
Treatment of tuberculosis typically requires the patient to take prescription drugs for six months or more. The general daily dose of rifampin, a first-line TB drug, is 10 mg/kg; but amounts of up to 35 mg/kg every day are safe for adults. Higher drug concentrations at infection sites could more efficiently kill pathogens, making treatments quicker and reducing the risk of failure, relapse and mortality.
Effective treatment of infections is based on achieving adequate levels of the antibiotic at the injection sites, where the microbes live. However, due to the challenges of directly sampling infected tissues, info on rifampin levels at infection sites has only been possible from tuberculosis patients with refractory disease, where resections are done to remove the infected parts.
Sanjay Jain, the Principal investigator and Alvaro Ordonez, the lead author of the Center for TB Research at Johns Hopkins University School of Medicine, defeated this challenge using PET/CT with 11C-rifampin, a radiolabelled analogue of rifampin.
The team conducted a multi-institutional study in 12 patients (nine men and three women, 19 to 77 years old) recently diagnosed with rifampin-susceptible pulmonary tuberculosis. Half of the patients had pulmonary cavitation, thick-walled abnormal reservations in the lung, and all had been receiving treatment for at least ten days prior to their PET/CT scan. The researchers made 1221 measurements, involving 473 from infected lung lesions and 748 from uninfected areas, including the lung, liver, plasma and brain.
By adopting a plasma pharmacokinetics model, the researchers used the PET data to assess the tissue-to-plasma AUC ratio for every pathologically distinct lesion. The model explained the distribution of 11C-rifampin into affected and unaffected lung regions utilising the concentration-time profiles collected from the PET data. CT results revealed that pulmonary lesions were heterogeneous in various lung regions of a patient. 11C-rifampin exposures in pulmonary tuberculosis lesions were low, spatially compartmentalised and demonstrated between- and within-patient variability. The 11C-rifampin AUC tissue-to-plasma ratios were most lacking in cavity walls, compared with other TB lesions or unaffected lungs.
"This non-invasive approach to measuring intralesional pharmacokinetics of antibiotics can also be utilised in other infections such as methicillin-resistant Staphylococcus aureus, or MRSA, which is often cured with long courses of rifampin", Jain says. "We would finally be able to ascertain the most effective doses of specific drugs in particular patients."
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