Nebulized Ceftazidime and Amikacin in Ventilator-associated Pneumonia Caused by <i>Pseudomonas aeruginosa</i>

Lü, Qin; Yang, Jing; Liu, Zhihai; Gutierrez, C. S.; Aymard, Guy; Rouby, Jean‐Jacques

doi:10.1164/rccm.201011-1894oc

Cited by 189 publications

(230 citation statements)

References 35 publications

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“…(1,2) Adjunctive aerosol antibiotic therapy to treat Gram-negative pneumonia in patients on mechanical ventilation has been studied for over 30 years with encouraging results; however, multicenter, placebocontrolled, randomized trials are needed to establish which antibiotics and drug delivery systems are most efficacious. (3)(4)(5)(6)(7)(8) The emergence of highly resistant Gram-negative bacteria has increased the amount of aminoglycoside required for a 1 Cardeas Pharma, Seattle, WA. 2 Alfred Hospital, Melbourne, Australia.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow^® Inline Nebulizer System in Mechanically Ventilated Patients

Ab¹,

Vallance²,

Abuan³

et al. 2014

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: This clinical trial evaluated the pharmacokinetics and safety/tolerability of amikacin/fosfomycin solution using a vibrating plate nebulizer, in mechanically ventilated patients with ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP). Methods: Nine adult patients were consented to receive three escalating doses of a combination of 50 mg/mL amikacin and 20 mg/mL fosfomycin; doses were separated by 24 -2 hr. On day 3, patients received two blinded, randomized treatments (amikacin/fosfomycin and volume-matched placebo), separated by 2 hr. All treatments were administered with a single-patient, multitreatment nebulizer (Investigational eFlow Ò Inline Nebulizer System; PARI Pharma GmbH, positioned in the inspiratory limb tubing between the ventilator and the patient. The nebulizer remained in-line until all treatments had been delivered. Concentrations of amikacin and fosfomycin were measured in tracheal aspirate and plasma samples obtained during the 24 hr after each dose. Results: Fifteen minutes after dosing with the 300/120 mg amikacin/fosfomycin combination, tracheal aspirate amikacin concentrations -SD were 12,390 -3,986 lg/g, and fosfomycin concentrations were 6,174 -2,548 lg/g (n¼6). Airway clearance was rapid. Plasma concentrations were subtherapeutic; the highest observed amikacin plasma concentration was 1.4 lg/mL, and the highest observed fosfomycin plasma concentration was 0.8 lg/mL. Administration time was approximately 2 min/mL. No adverse effects on respiratory rate, peak airway pressures, or oxygenation were observed during or following drug or placebo administration. Conclusions: High tracheal aspirate concentrations of amikacin and fosfomycin were achieved in mechanically ventilated patients with VAT or VAP after aerosolized administration with an inline nebulizer system. Airway clearance was rapid. No adverse respiratory effects were noted during or following drug administration.

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Section: Introductionmentioning

confidence: 99%

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow^® Inline Nebulizer System in Mechanically Ventilated Patients

Ab¹,

Vallance²,

Abuan³

et al. 2014

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…5,[25][26][27][28][29][30] In a recent clinical trial of antibiotics nebulization, obstruction of the expiratory filter occurred in 3 patients of a 20-patient cohort, and caused cardiac arrest in 1 patient. 21 Our results suggest that the increase in expiratory resistance is due mainly to filter saturation by water condensates. That finding is relevant to hygrometric measurements at the distal end of the expiratory limb.…”

Section: Discussionmentioning

confidence: 60%

“…10,21 The increase in the resistance of an expiratory filter over time is due mainly to the humidification circuit type, rather than to nebulization. If expiratory limb filtration is mandatory during mechanical ventilation, it may require the use of specifically dedicated filtering devices, and/or heated expiratory limbs.…”

Section: Discussionmentioning

confidence: 99%

Impact of Humidification and Nebulization During Expiratory Limb Protection: An Experimental Bench Study

et al. 2012

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BACKGROUND: Different filtering devices are used during mechanical ventilation to avoid dysfunction of flow and pressure transducers or for airborne microorganisms containment. Water condensates, resulting from the use of humidifiers, but also residual nebulization particles may have a major influence on expiratory limb resistance. OBJECTIVES: To evaluate the influence of nebulization and active humidification on the resistance of expiratory filters. METHODS: A respiratory system analog was constructed using a test lung, an ICU ventilator, heated humidifiers, and a piezoelectric nebulizer. Humidifiers were connected to different types of circuits (unheated, mono-heated, new-generation and old-generation bi-heated). Five filter types were evaluated: electrostatic, heat-and-moisture exchanger, standard, specific, and internal heated high-efficiency particulate air [HEPA] filter. Baseline characteristics were obtained from each dry filter. Differential pressure measurements were carried out after 24 hours of continuous in vitro use for each condition, and after 24 hours of use with an old-generation bi-heated circuit without nebulization. RESULTS: While using unheated circuits, measurements had to be interrupted before 24 hours for all the filtering devices except the internal heated HEPA filter. The heat-and-moisture exchangers occluded before 24 hours with the unheated and mono-heated circuits. The circuit type, nebulization practice, and duration of use did not influence the internal heated HEPA filter resistance. CONCLUSION: Expiratory limb filtration is likely to induce several major adverse events. Expiratory filter resistance increase is due mainly to the humidification circuit type, rather than to nebulization. If filtration is mandatory while using an unheated circuit, a dedicated filter should be used for < 24 hours, or a heated HEPA for a longer duration.

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“…β-lactam antibiotics, aminoglycosides, macrolides, clindamycin and tetracyclines were not recommended to treat critically ill patients. [14] Teicoplanin and linezolide against multi-resistant bacteria were very effective to multidrug resistant bacteria, just as vancomycin.…”

Section: Discussionmentioning

confidence: 99%

Distribution and antibiotic resistance of pathogens isolated from ventilator-associated pneumonia patients in pediatric intensive care unit

et al. 2011

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Nebulized Ceftazidime and Amikacin in Ventilator-associated Pneumonia Caused by Pseudomonas aeruginosa

Cited by 189 publications

References 35 publications

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow^® Inline Nebulizer System in Mechanically Ventilated Patients

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow^® Inline Nebulizer System in Mechanically Ventilated Patients

Impact of Humidification and Nebulization During Expiratory Limb Protection: An Experimental Bench Study

Distribution and antibiotic resistance of pathogens isolated from ventilator-associated pneumonia patients in pediatric intensive care unit

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Nebulized Ceftazidime and Amikacin in Ventilator-associated Pneumonia Caused by Pseudomonas aeruginosa

Cited by 189 publications

References 35 publications

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow® Inline Nebulizer System in Mechanically Ventilated Patients

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow® Inline Nebulizer System in Mechanically Ventilated Patients

Impact of Humidification and Nebulization During Expiratory Limb Protection: An Experimental Bench Study

Distribution and antibiotic resistance of pathogens isolated from ventilator-associated pneumonia patients in pediatric intensive care unit

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A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow^® Inline Nebulizer System in Mechanically Ventilated Patients

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow^® Inline Nebulizer System in Mechanically Ventilated Patients