Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study
Abstract
Background Individuals with cystic fibrosis (CF) receive antibiotics continuously throughout their entire life which leads to drug resistant microbial lung infections which are difficult to treat. Nitric oxide (NO) gas possesses antimicrobial activity against a wide variety of microorganisms in vitro, in vivo in animal models and a phase I study in healthy adults showed administration of intermittent 160 ppm NO to be safe. Methods We assessed feasibility and safety of inhaled NO in eight CF patients who received 160 ppm NO for 30 min, three times daily for 2 periods of 5 days. Results The NO treatment was safe and in none of the patients were serious drug-related adverse events observed which caused termination of the study. The intention-to-treat analysis revealed a significant mean reduction of the colony forming units of all bacteria and all fungi, while mean forced expiratory volume 1 s % predicted (FEV1) relative to baseline increased 17.3 ± 8.9 % (P = 0.012). Conclusions NO treatment may improve the therapy of chronic microbial lung infections in CF patients, particularly concerning pathogens with intrinsic or acquired resistance to antibiotics.
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NO has been evaluated as a therapy in a variety of bacterial and fungal infections, including infections by Pseudomonas aeruginosa in cases of cystic fibrosis and infections caused by dermatophytes.
“NO has been evaluated as a therapy in a variety of bacterial and fungal infections, including infections by Pseudomonas aeruginosa in cases of cystic fibrosis and infections caused by dermatophytes (22–24).”
From Inhibition of Classical and Alternative Modes of Respiration in <i>Candida albicans</i> Leads to Cell Wall Remodeling and Increased Macrophage Recognition (2019) · cites this paper as [22]
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- Authors
- Deppisch, C., Herrmann, G., Graepler-Mainka, U., Wirtz, H., Heyder, S., Engel, C., Marschal, M., Miller, C. C., & Riethmüller, J.
- Affiliations
- University Children's Hospital Tübingen (DE)
- University Hospital Leipzig (DE)
- Robert Bosch Hospital (DE)
- Universitätsklinikum Tübingen (DE)
- University of British Columbia (CA)
- Corresponding author
- Riethmüller, Joachim
- ORCID
- Engel, Corinna
- Venue
- Infection
- Published
- 2016-02-09
- Volume
- 44
- Issue
- 4
- Pages
- 513-520
- ISSN
- 0300-8126 (ISSN-L)
- 1439-0973
- OpenAlex
- W2254558178
- Cited by
- 115
- References
- 34
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 6 · 2023: 20 · 2022: 10 · 2021: 15 · 2020: 20 · 2019: 13 · 2018: 8 · 2017: 7
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Infection (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Real-Fund, Linde AG, Munich, Germany
- Förderverein Mukoviszidose eV Neckar Alb, Dettingen
- Mukoviszidose eV Baden-Württemberg, Germany
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- nitric oxide, inhaled nitric oxide, cystic fibrosis, antibiotic resistance, bacterial lung infection, fungal lung infection, antimicrobial activity, treatment safety, forced expiratory volume, chronic lung infection
- MeSH terms
- Adult, Anti-Infective Agents, Cystic Fibrosis, Feasibility Studies, Female, Forced Expiratory Volume, Humans, Male, Nitric Oxide, Respiratory Tract Infections, Drug Resistance, Bacterial, Drug Resistance, Fungal
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