Combination Therapy to Combat Cavitary Tuberculosis Monalisha Debnath1, Sujit Kumar Debnath2, Rohit Srivastava2,* 1Department of Electrical Engineering, Indian Institute of Technology, Kharagpur, West Bengal, India; 2,*Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India. *Corresponding author Tuberculosis continues to be a major threat to global health. Cavitation is a dangerous consequence of pulmonary tuberculosis associated with poor outcomes, treatment relapse, higher transmission rates, and development of drug resistance. Patients with cavity have a bacterial load of up to 1011 bacilli/gram, making it highly contagious. First-line and second-line therapy for tuberculosis are available. However, these drugs cannot reach the lungs from conventional dosage forms (tablets, capsules, and injection). So there is a research gap in the effective management of cavitary tuberculosis. There is a need for targeted delivery to concentrate the drug more in the lungs. By using inhalation therapy, we can improve the availability of anti-tubercular drugs in the cavitary site. However, these drugs cannot penetrate the cavity. One of the most promising reasons behind this type of TB is inflammation. Inflammation alters cell physiology. Hence, a combination of anti-inflammatory agents with the anti-tubercular drug will be a promising therapy for cavitary tuberculosis. In most cases, chemotherapy is not tissue-specific. Therefore, the drug is distributed throughout the body or non-specific. Thus, host-directed therapy will be another promising approach for this type of TB. Oxidative stress and overproduction of reactive oxygen species are the main key factor for the initiation of diseases like tuberculosis. Therefore proper regulation of ROS is highly essential, particularly in this type of TB. We have prepared the ethionamide (second-line anti-tubercular drugs) nanoparticles in the lab and modified them into a dry powder inhaler for pulmonary administration. In an animal study, this DPI was successfully delivered to the lung and sustained the action for more than 24 hr. Drug concentration in the lungs was maintained above minimum inhibitory concentration (MIC) for more than 12 hr. Hence, a twice-daily dose would able to maintain the drug concentration above MIC for 24 hr. A combination of ethionamide with other anti-inflammatory drugs or ROS regulatory agents will improve the treatment of cavitary tuberculosis.