title: 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.
authors: Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany.
authors: Caroline
authors: C
authors: Deppisch
authors: Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany.
authors: Gloria
authors: G
authors: Herrmann
authors: Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany.
authors: Ute
authors: U
authors: Graepler-Mainka
authors: Medizinische Klinik I, Pneumologie, Universität Leipzig, Leipzig, Germany.
authors: Hubertus
authors: H
authors: Wirtz
authors: Klinik Schillerhöhe, Robert Bosch Krankenhaus GmbH, Gerlingen, Germany.
authors: Susanne
authors: S
authors: Heyder
authors: Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany.
authors: Corinna
authors: C
authors: Engel
authors: Institute of Medical Microbiology and Hygiene, Universitätsklinikum Tübingen, Tübingen, Germany.
authors: Matthias
authors: M
authors: Marschal
authors: Nitric Oxide Laboratory, Division of Respiratory and Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors: Christopher C
authors: CC
authors: Miller
authors: Comprehensive Cystic Fibrosis Center, Children's Clinic, Tübingen, Germany. joachim.riethmueller@med.uni-tuebingen.de.|University Childrens' Hospital, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 1, 72076, Tübingen, Germany. joachim.riethmueller@med.uni-tuebingen.de.
authors: Joachim
authors: J
authors: Riethmüller
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications*; D024881:Drug Resistance, Bacterial; D025141:Drug Resistance, Fungal; D005240:Feasibility Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D009569:Nitric Oxide
keywords: Antimicrobial; Cystic fibrosis; Lung infection; Nitric oxide