# Inhaled tigecycline therapy for pulmonary M. abscessus infections

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2024 · $627,834

## Abstract

Summary
Mycobacterium abscessus (MAB) is a nontuberculous mycobacterium that causes chronic pulmonary infections
(pMAB) and patients with pre-existing lung disease (especially cystic fibrosis patients) have a predisposition to
pMAB. Due to MAB’s intrinsic antibiotic resistance, treatment is often complex and with low cure rates.
Tigecycline, a glycylcycline class antibiotic, demonstrates bactericidal effects against pMAB without eliciting
bacterial resistance mechanisms. For pMAB treatment, patients receive twice daily intravenous administration
of tigecycline during at least one month resulting in significant side effects and many patients withdraw from
treatment. Tigecycline has the potential to qualify as the first-line agent during therapy for pMAB and the
backbone for new combination regimens but to achieve its fullest therapeutic potential, we need to improve
tigecyclines ratio between efficacy and safety/tolerability, i.e. its therapeutic index. One approach to address this
challenge is to develop inhalational formulations of tigecycline that are easy to administer and are well
tolerated. In preliminary studies, GM-CSF KO mice with pMAB were treated by intrapulmonary aerosols of
tigecycline for 28 days. The pulmonary bacterial burden after full treatment duration showed that inhaled
tigecycline has high, dose-dependent efficacy, and is well tolerated. Here we hypothesize that aerosol delivery
of tigecycline is a viable therapeutic approach for pMAB. In Aim 1, to avoid the tigecycline requirements for
reconstitution, we will develop a dry powder formulation of tigecycline with well characterized aerodynamic
properties suitable for inhalation. Aim 2 will study the relationship between dose, dosing regimen and resulting
exposure of aerosols of tigecycline in different body fluids, organs and tissues. In particular, we will study the
dose-exposure relationship of inhaled versus intravenous tigecycline and its availability in plasma, lung,
abscesses and epithelial lining fluid. In Aim 3, we propose to test the efficacy, dose, dosing frequency, and
duration of inhaled tigecycline against pMAB using animal models. We propose using first the GM-CSF KO
murine model, subsequently, we will test the best regimen in b-ENac Tg mice with pMAB infection, as a
representative model for cystic fibrosis patients. The best regimen will be validated in mice infected with selected
clinical isolates from MAB clones 1 and 2 and isolates obtained from cystic fibrosis patients. Aim 4 will
determine efficacy of inhaled tigecycline in multidrug therapies. Mice with pMAB as in Aim 3 (with strain
#21 or clinical isolates) will be treated with binary or ternary combinations of inhaled tigecycline and
clarithromycin (oral), clofazimine (oral), bedaquiline (oral). These studies will be performed by a consortium of
experts located at Colorado State University, University of Tennessee, Research Triangle Institute and National
Jewish Hospital. Working together, we aim to prov...

## Key facts

- **NIH application ID:** 10853012
- **Project number:** 5R01AI155922-04
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Mercedes Gonzalez-Juarrero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $627,834
- **Award type:** 5
- **Project period:** 2021-06-29 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853012

## Citation

> US National Institutes of Health, RePORTER application 10853012, Inhaled tigecycline therapy for pulmonary M. abscessus infections (5R01AI155922-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10853012. Licensed CC0.

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