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Nebulized ceftazidime in experimental pneumonia caused by partially resistant Pseudomonas aeruginosa
Fabio Ferrari1, Qin Lu, Cassio Girardi
1Réanimation Polyvalente Pierre Viars, Département d'Anesthésie-Réanimation, UPMC Univ Paris 06, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83 boulevard de l'Hôpital, 75013, Paris, France.
Purpose:
Ventilator-associated pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime is frequent in critically ill patients. The aim of the study was to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administrations of ceftazidime in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime.
Methods:
Ceftazidime was administered 24 h following the intra-bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration = 16 microg ml(-1)), either by nebulization (25 mg kg(-1) every 3 h, n = 6) or by continuous intravenous infusion (90 mg kg(-1) over 24 h after an initial rapid infusion of 30 mg kg(-1), n = 6). Four non-treated inoculated animals served as controls. All piglets were killed 48 h (intravenous and control groups) or 51 h (aerosol group) after inoculation. Lung tissue concentrations and lung bacterial burden were assessed on multiple post-mortem sub-pleural lung specimens [(lower limit of quantitation = 10(2) colony forming unit (cfu g(-1))].
Results:
Ceftazidime trough lung tissue concentrations following nebulization were greater than steady-state lung tissue concentrations following continuous intravenous infusion [median and interquartile range, 24.8 (12.6-59.6) microg g(-1) vs. 6.1 (4.6-10.8) microg g(-1)] (p < 0.001). After 24 h of ceftazidime administration, 83% of pulmonary segments had bacterial counts <10(2) cfu g(-1) following nebulization and only 30% following intravenous administration (p < 0.001). In control animals, 10% of lung segments had bacterial counts <10(2) cfu g(-1) 48 h following bronchial inoculation.
Conclusion:
Nebulized ceftazidime provides more efficient bacterial killing in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime.
Insights
Nebulized ceftazidime achieved higher lung concentrations and better bacterial killing in piglets with Pseudomonas aeruginosa pneumonia compared to intravenous administration. This suggests nebulization may be a more effective delivery method for this infection.
Area of Science:
- Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients.
- Pseudomonas aeruginosa infections, particularly those with reduced susceptibility to standard antibiotics like ceftazidime, pose a significant therapeutic challenge.
- Effective antibiotic delivery to lung tissue is crucial for treating VAP.
Purpose of the Study:
- To compare the lung tissue deposition and antibacterial efficacy of nebulized versus intravenous ceftazidime.
- To evaluate these administration routes in a preclinical model of ventilator-associated pneumonia caused by ceftazidime-resistant Pseudomonas aeruginosa.
Main Methods:
- The study utilized a ventilated piglet model inoculated with Pseudomonas aeruginosa (minimum inhibitory concentration = 16 µg/mL).
- Ceftazidime was administered either via nebulization (25 mg/kg every 3 hours) or continuous intravenous infusion (90 mg/kg over 24 hours).
- Lung tissue ceftazidime concentrations and bacterial burden were quantified post-mortem.
Main Results:
- Nebulized ceftazidime resulted in significantly higher trough lung tissue concentrations compared to intravenous administration (24.8 µg/g vs. 6.1 µg/g).
- Bacterial eradication was more effective with nebulization, with 83% of lung segments showing counts below 10^2 CFU/g after 24 hours, versus 30% with intravenous administration.
- Control animals showed minimal bacterial reduction.
Conclusions:
- Nebulized ceftazidime demonstrates superior antibacterial efficiency in the piglet model of VAP caused by Pseudomonas aeruginosa with impaired ceftazidime sensitivity.
- Direct lung delivery via nebulization may offer a promising strategy for managing challenging VAP cases.
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