Use of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection
Nontuberculous mycobacterium (NTM) infections are challenging to manage and are frequently non-responsive to aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients are susceptible to NTM infections and poor patient outcomes are common. Bacteriophages present an alternative treatment option and are associated with favorable clinical outcomes. Similarly, dual beta-lactam combinations show promise in vitro, but clinical use is sparse. We report here a patient with an uncontrolled Mycobacterium abscessus infection following a bilateral lung transplant and failed antibiotic therapy. Both smooth and rough colony morphotype strains were initially present, but treatment with two phages that kill the rough strain - including epigenetic-modification to overcome restriction - resulted in isolation of only the smooth strain. The rough and smooth strains have similar antibiotic susceptibilities suggesting that the phages specifically eliminated the rough strain. Dual beta-lactam therapy with meropenem and ceftazidime-avibactam provided further clinical improvement, and the phages act synergistically with meropenem in vitro.
Authors
- Michael J. Lauer (ORCID: https://orcid.org/0009-0001-6118-1429)
- Ellen M. Mowry (ORCID: https://orcid.org/0000-0003-0623-5188)
- Daniel A. Russell (ORCID: https://orcid.org/0000-0001-6894-2748)
- Elena Shashkina
- Brent Footer (ORCID: https://orcid.org/0000-0002-8585-1722)
- Leonard J. Lobo
- Deborah Jacobs‐Sera (ORCID: https://orcid.org/0000-0001-7838-3257)
- Madison Cristinziano
- Rebecca A. Garlena (ORCID: https://orcid.org/0000-0003-3245-2629)
- Melissa B. Miller (ORCID: https://orcid.org/0000-0002-0296-3535)
- Barry N. Kreiswirth (ORCID: https://orcid.org/0000-0002-0243-131X)
- Anne Friedland
- Christina T. Doligalski (ORCID: https://orcid.org/0000-0001-6688-8573)
- Graham F. Hatfull (ORCID: https://orcid.org/0000-0002-6705-6821)
- David van Duin (ORCID: https://orcid.org/0000-0003-4784-3227)
- Luther A. Bartelt (ORCID: https://orcid.org/0000-0002-7596-4272)
- Maggie Viland (ORCID: https://orcid.org/0009-0007-7089-4854)
- Lawrence Abad (ORCID: https://orcid.org/0000-0002-8915-9506)
- Ari Kaganovsky
- Liang Chen (ORCID: https://orcid.org/0000-0001-5845-2235)
- Jun Xiao (ORCID: https://orcid.org/0000-0002-2222-967X)
- Raymond D. Coakley
Institutions
- University of North Carolina at Chapel Hill (US)
- University of North Carolina Health Care (US)
- University of Pittsburgh (US)
- Center for Discovery (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41467-024-54666-4
- Citations
- 18
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 8.26
Funders
- Howard Hughes Medical Institute
- Cystic Fibrosis Foundation
- National Institutes of Health