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Published on: January 22, 2021
Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa
Qin Lu1, Jianxin Yang, Zhihai Liu
1Multidisciplinary Intensive Care Unit Pierre Viars, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
Rationale:
In experimental pneumonia, nebulization of antibiotics provides high lung tissue concentrations and rapid bacterial killing.
Objectives:
To assess the efficacy and safety of nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa.
Methods:
Forty patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa were included in a randomized comparative phase II trial. Twenty patients infected with susceptible or intermediate strains received nebulized ceftazidime (15 mg·kg(-1)·3 h(-1)) and amikacin (25 mg·kg(-1)·d(-1)). Seventeen patients infected with susceptible strains received intravenous ceftazidime (90 mg·kg(-1)·d(-1), continuous administration) and amikacin (15 mg·kg(-1)·d(-1)). In three patients infected with intermediate strains, amikacin was replaced by ciprofloxacin (400 mg·12 h(-1)).
Measurements And Main Results:
After 8 days of antibiotic administration, aerosol and intravenous groups were similar in terms of successful treatment (70 vs. 55%), treatment failure (15 vs. 30%), and superinfection with other microorganisms (15 vs. 15%). Antibiotic-induced changes in lung aeration, determined by computed tomography, were not different between groups (increase in gas volume, 159 ± 460 vs. 251 ± 583 ml; decrease in tissue volume, -58 [-77, 25] vs. -89 [-139, 5] ml). Acquisition of per-treatment antibiotic resistance was observed exclusively in the intravenous group. In the aerosol group, four patients infected with intermediate strains were successfully treated. Nebulization induced an obstruction of the expiratory filter in three patients. The obstruction caused cardiac arrest in one patient, who fully recovered after brief cardiopulmonary resuscitation.
Conclusions:
Nebulization and intravenous infusion of ceftazidime and amikacin provide similar efficiency for treating ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Nebulization is efficient against intermediate strains and may prevent per-treatment acquisition of antibiotic resistance.
Insights
Nebulized antibiotics ceftazidime and amikacin show similar efficacy to intravenous administration for treating ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Nebulization is effective against resistant strains and may prevent antibiotic resistance acquisition.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Pharmacology
Background:
- Nebulization of antibiotics in experimental pneumonia models achieves high lung concentrations and rapid bacterial killing.
- Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is a significant clinical challenge.
Purpose of the Study:
- To evaluate the efficacy and safety of nebulized ceftazidime and amikacin compared to intravenous administration for treating VAP caused by Pseudomonas aeruginosa.
Main Methods:
- A randomized comparative phase II trial included 40 patients with VAP due to Pseudomonas aeruginosa.
- Patients received either nebulized ceftazidime and amikacin or intravenous ceftazidime and amikacin (with ciprofloxacin substitution in some cases).
- Treatment outcomes, lung aeration changes via CT scan, and antibiotic resistance acquisition were assessed.
Main Results:
- Successful treatment rates were comparable between nebulized (70%) and intravenous (55%) groups.
- No significant differences in lung aeration changes were observed between the groups.
- Antibiotic resistance acquisition occurred only in the intravenous group; nebulization was effective against intermediate strains.
Conclusions:
- Nebulization and intravenous administration of ceftazidime and amikacin demonstrate similar efficacy in treating Pseudomonas aeruginosa VAP.
- Nebulized antibiotics are effective against intermediate strains and may reduce the development of antibiotic resistance during treatment.
- Nebulization is a viable alternative route for antibiotic delivery in VAP, with a potential benefit in preventing resistance.
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