Use of Adjunctive Aerosolized Antimicrobial Therapy in the Treatment of<i>Pseudomonas aeruginosa</i>and<i>Acinetobacter baumannii</i>Ventilator-Associated Pneumonia

Arnold, Heather; Sawyer, Amber M; Kollef, Marin H.

doi:10.4187/respcare.01556

Cited by 84 publications

(58 citation statements)

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“…With the evidence that is available today, the recommendation for concomitant treatment should remain for patients with MDR pathogens and in cases in which systemic antibiotics were not effective. [60][61][62][63][64] …”

Section: Aerosolized Antibiotics In Combination With Systemic Antibiomentioning

confidence: 99%

Aerosolized Antibiotics

2015

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Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

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Section: Aerosolized Antibiotics In Combination With Systemic Antibiomentioning

confidence: 99%

Aerosolized Antibiotics

2015

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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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“…The results of small retrospective studies are conflicting, as demonstrated by other studies with improved survival with concomitant administration of aerosolised and i.v. colistin in patients with VAP [26]. Pooling the data of relevant clinical studies, adjunctive aerosolised colistin therapy did not reach statistically significant results compared with i.v.…”

Section: Colistinmentioning

confidence: 84%

Treatment of extensively drug-resistant Gram-negative infections in critically ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of Clinical Microbiology and Infection, October 2012

Tambyah

Hara

Daikos

et al. 2013

Journal of Global Antimicrobial Resistance

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Use of Adjunctive Aerosolized Antimicrobial Therapy in the Treatment ofPseudomonas aeruginosaandAcinetobacter baumanniiVentilator-Associated Pneumonia

Abstract: Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

Cited by 84 publications

References 20 publications

Aerosolized Antibiotics

Aerosolized Antibiotics

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

Treatment of extensively drug-resistant Gram-negative infections in critically ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of Clinical Microbiology and Infection, October 2012

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Use of Adjunctive Aerosolized Antimicrobial Therapy in the Treatment ofPseudomonas aeruginosaandAcinetobacter baumanniiVentilator-Associated Pneumonia

Abstract: Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

Cited by 84 publications

References 20 publications

Aerosolized Antibiotics

Aerosolized Antibiotics

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

Treatment of extensively drug-resistant Gram-negative infections in critically ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of Clinical Microbiology and Infection, October 2012

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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