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). Conclusion 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.

Background Lung auscultation and bedside chest radiography are routinely used to assess the respiratory condition of ventilated patients with acute respiratory distress syndrome (ARDS). Clinical experience suggests that the diagnostic accuracy of these procedures is poor. Methods This prospective study of 32 patients with ARDS and 10 healthy volunteers was performed to compare the diagnostic accuracy of auscultation, bedside chest radiography, and lung ultrasonography with that of thoracic computed tomography. Three pathologic entities were evaluated in 384 lung regions (12 per patient): pleural effusion, alveolar consolidation, and alveolar-interstitial syndrome. Results Auscultation had a diagnostic accuracy of 61% for pleural effusion, 36% for alveolar consolidation, and 55% for alveolar-interstitial syndrome. Bedside chest radiography had a diagnostic accuracy of 47% for pleural effusion, 75% for alveolar consolidation, and 72% for alveolar-interstitial syndrome. Lung ultrasonography had a diagnostic accuracy of 93% for pleural effusion, 97% for alveolar consolidation, and 95% for alveolar-interstitial syndrome. Lung ultrasonography, in contrast to auscultation and chest radiography, could quantify the extent of lung injury. Interobserver agreement for the ultrasound findings as assessed by the kappa statistic was satisfactory: 0.74, 0.77, and 0.73 for detection of alveolar-interstitial syndrome, alveolar consolidation, and pleural effusion, respectively. Conclusions At the bedside, lung ultrasonography is highly sensitive, specific, and reproducible for diagnosing the main lung pathologic entities in patients with ARDS and can be considered an attractive alternative to bedside chest radiography and thoracic computed tomography.

Background Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration. Methods An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections. Results Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 microg/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 microg/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 microg/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 microg/g in lung segments with lung aeration of 50% or more. Conclusions In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose. The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments.