Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: comparative effects of helium and nitrogen.
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.
Tonnellier
Marc
M
Réanimation Chirurgicale Pierre Viars, Département d'Anesthésie, Hôpital de la Pitié-Salpétrière (University of Paris 6), Paris, France.
Ferrari
Fabio
F
Goldstein
Ivan
I
Sartorius
Alfonso
A
Marquette
Charles-Hugo
CH
Rouby
Jean-Jacques
JJ
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
D002511:Cephalosporins; D006371:Helium; D002442:Ceftazidime; D010100:Oxygen