Nontuberculous Mycobacteria (NTM) Therapy Research
Nontuberculous mycobacteria (NTM) cause chronic lung infections that are difficult to treat. Mycobacterium abscessus infections are particularly challenging, with cure rates of only ~50%. Antimicrobial therapy is often required for months to over a year to slow disease progression. Unfortunately, treatment-related toxicities are common and may be life-limiting, including deafness and kidney damage. Better therapeutic solutions are urgently needed.
Treatment of NTM infections relies on combinations of three or more antimicrobials. However, these regimens are typically selected based on susceptibility testing of individual drugs in isolation, without accounting for how multiple agents may interact to enhance or diminish one another’s activity.
Using advanced experimental systems, the Kirby Laboratory is testing the effects of two, three, or more drugs in combination to identify regimens with improved therapeutic potential. Most routine antibiotic testing is performed under static conditions, in which drugs are added at fixed concentrations to organisms in liquid culture. In contrast, in humans, antibiotic concentrations rise rapidly after dosing and then decline over time according to drug-specific half-lives. This pulsatile drug exposure is described by pharmacokinetics (PK).
Because standard laboratory assays do not replicate pulsatile PK, they are often less predictive of clinical efficacy. To address this limitation, we have implemented the Hollow Fiber Infection Model (HFIM). In this system, bacteria are confined within a compartment separated by a semi-permeable membrane with a large surface area that allows antibiotics and nutrients to diffuse freely while retaining organisms for viability assessment.
On the opposing side of the membrane, media are continuously circulated to precisely reproduce human PK profiles for individual drugs or combinations. Using automated syringe pumps, we can model clinically relevant exposure patterns for three or four antimicrobials administered as they would be in patients. This approach is highly predictive of human treatment outcomes.
Through these and related methods, our goal is to develop safer, simpler, and more effective combination therapies for devastating infections caused by M. abscessus and other NTM species.
Selected Recent Publications
Huang Y, Truelson KA, Stewart IA, O'Doherty GA, Kirby JE. Enhanced Activity of Apramycin and Apramycin-Based Combinations Against Mycobacteroides abscessus. J Antimicrob Chemother. 2026 Jan 6;81(1):dkaf433. doi: 10.1093/jac/dkaf433. PMID: 41313250; PMCID: PMC12802941.
Huang Y, Chiaraviglio L, Bode-Sojobi I, Kirby JE. Triple antimicrobial combinations with potent synergistic activity against M. abscessus. Antimicrob Agents Chemother. 2025 Apr 2;69(4):e0182824. doi: 10.1128/aac.01828-24. Epub 2025 Mar 14. PMID: 40084880; PMCID: PMC11963555.
Support our work
Please consider donating to support our efforts to advance treatment of NTM infections. Donations may be made by credit card through Beth Israel Deaconess Medical Center.
Under "Gift Information, " please check "Select Gift Designation" , scroll to the bottom of the list, then select "Other" and specify "Research Laboratory of James Kirby, Dept. of Pathology".
Thank you for your support.
Treatment of NTM infections relies on combinations of three or more antimicrobials. However, these regimens are typically selected based on susceptibility testing of individual drugs in isolation, without accounting for how multiple agents may interact to enhance or diminish one another’s activity.
Using advanced experimental systems, the Kirby Laboratory is testing the effects of two, three, or more drugs in combination to identify regimens with improved therapeutic potential. Most routine antibiotic testing is performed under static conditions, in which drugs are added at fixed concentrations to organisms in liquid culture. In contrast, in humans, antibiotic concentrations rise rapidly after dosing and then decline over time according to drug-specific half-lives. This pulsatile drug exposure is described by pharmacokinetics (PK).
Because standard laboratory assays do not replicate pulsatile PK, they are often less predictive of clinical efficacy. To address this limitation, we have implemented the Hollow Fiber Infection Model (HFIM). In this system, bacteria are confined within a compartment separated by a semi-permeable membrane with a large surface area that allows antibiotics and nutrients to diffuse freely while retaining organisms for viability assessment.
On the opposing side of the membrane, media are continuously circulated to precisely reproduce human PK profiles for individual drugs or combinations. Using automated syringe pumps, we can model clinically relevant exposure patterns for three or four antimicrobials administered as they would be in patients. This approach is highly predictive of human treatment outcomes.
Through these and related methods, our goal is to develop safer, simpler, and more effective combination therapies for devastating infections caused by M. abscessus and other NTM species.
Selected Recent Publications
Huang Y, Truelson KA, Stewart IA, O'Doherty GA, Kirby JE. Enhanced Activity of Apramycin and Apramycin-Based Combinations Against Mycobacteroides abscessus. J Antimicrob Chemother. 2026 Jan 6;81(1):dkaf433. doi: 10.1093/jac/dkaf433. PMID: 41313250; PMCID: PMC12802941.
Huang Y, Chiaraviglio L, Bode-Sojobi I, Kirby JE. Triple antimicrobial combinations with potent synergistic activity against M. abscessus. Antimicrob Agents Chemother. 2025 Apr 2;69(4):e0182824. doi: 10.1128/aac.01828-24. Epub 2025 Mar 14. PMID: 40084880; PMCID: PMC11963555.
Support our work
Please consider donating to support our efforts to advance treatment of NTM infections. Donations may be made by credit card through Beth Israel Deaconess Medical Center.
Under "Gift Information, " please check "Select Gift Designation" , scroll to the bottom of the list, then select "Other" and specify "Research Laboratory of James Kirby, Dept. of Pathology".
Thank you for your support.