Pioneering new regimens to treat mycobacterium avium complex pulmonary disease

The National Institute of Allergy and Infectious Diseases awarded The Johns Hopkins University $703,040 on August 27, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop innovative treatment regimens for Mycobacterium avium complex pulmonary disease.

The research addresses a critical gap in MAC lung disease treatment, where current therapies achieve only a 31 percent three-year microbiological cure rate and only one FDA-approved drug exists. The project pursues three specific aims. Aim 1 develops new multidrug regimens compliant with current guidelines using a validated mouse model of MAC lung disease, evaluating antibiotic combinations that minimize drug resistance and treatment failure. Aim 2 investigates dual beta-lactams with synergistic activity against MAC, testing beta-lactam pairs in vitro and in mouse models to establish efficacy. Aim 3 challenges the current requirement for multidrug regimens by testing simplified, phase-specific regimens using one or two highly synergistic drugs, with preliminary data suggesting these may achieve equivalent or superior efficacy compared to standard multidrug approaches.

The award funds work performed in Baltimore, Maryland, with a period of performance through August 31, 2027. The assistance type is a Project Grant.

Abstract

The global incidence of non-tuberculous mycobacterial lung disease, particularly caused by mycobacterium avium complex (MAC), has surpassed tuberculosis (TB) in the U.S. MAC primarily affects individuals with underlying lung conditions or compromised immunity, leading to rapid lung function decline and significant morbidity and mortality. Unlike TB, which benefits from multiple FDA-approved drugs and extensive research, MAC lung disease has only one FDA-approved drug (amikacin), and current treatments achieve a 3-year microbiological cure rate of just 31%. This proposal aims to develop innovative, effective regimens for MAC lung disease by leveraging novel concepts and emerging evidence to address critical gaps in treatment. Specific aim 1 focuses on developing new regimens compliant with current guidelines requiring three or more drugs. Using a validated mouse model of MAC lung disease, the study will evaluate combinations of existing and new antibiotics prioritizing regimens that minimize drug resistance and treatment failure. Specific aims 2 and 3 pursue pioneering ideas to innovate radically different treatment approaches. Specific aim 2 investigates dual β-lactams with synergistic activity against MAC. Building on emerging evidence, this aim seeks to identify and test β-lactam pairs in vitro and in mouse models to establish their efficacy for MAC lung disease. Specific aim 3 challenges the need for multidrug regimens in both treatment phases. Preliminary data suggest that simplified, phase-specific regimens using one or two highly synergistic drugs may achieve equivalent or superior efficacy. This aim will rigorously test these regimens to determine their potential to transform clinical practices. If successful, this research will redefine MAC lung disease treatment by delivering optimized regimens that improve outcomes and establish a new standard of care.