title: Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: comparative effects of helium and nitrogen.
abstract: BACKGROUND
  Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia.
  
  
  METHODS
  Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography.
  
  
  RESULTS
  As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 +/- 13 vs. 383 +/- 84 microg/g in noninfected piglets and 10 +/- 3 vs. 129 +/- 108 microg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 +/- 141 microg/g; P < 0.001) and no significant change in infected piglets (111 +/- 104 microg/g).
  
  
  CONCLUSIONS
  Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia.
authors.affiliation: Réanimation Chirurgicale Pierre Viars, Département d'Anesthésie, Hôpital de la Pitié-Salpétrière (University of Paris 6), Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Tonnellier
authors.forename: Fabio
authors.initials: F
authors.lastname: Ferrari
authors.forename: Ivan
authors.initials: I
authors.lastname: Goldstein
authors.forename: Alfonso
authors.initials: A
authors.lastname: Sartorius
authors.forename: Charles-Hugo
authors.initials: CH
authors.lastname: Marquette
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Rouby
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D001996:Bronchopneumonia / Q000378:metabolism* / Q000503:physiopathology; D002442:Ceftazidime / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004927:Escherichia coli Infections / Q000378:metabolism; D006371:Helium / Q000494:pharmacology*; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D010100:Oxygen / Q000494:pharmacology*; D010316:Particle Size; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000502:physiology; D013552:Swine; D014465:Ultrasonics
chemical_list: D002511:Cephalosporins; D006371:Helium; D002442:Ceftazidime; D010100:Oxygen