Trial reportJournal of aerosol medicine and pulmonary drug delivery2014
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.
Trial report in Journal of aerosol medicine and pulmonary drug delivery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 3 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Pooled it
- "Nebulized lidocaine for intractable cough in hospice care: a comprehensive review of efficacy, safety, and future perspectives".BMC palliative care · 2025Pooled it
- Aerosol delivery during invasive mechanical ventilation: a systematic review.Critical care (London, England) · 2017Pooled it
- Amikacin pharmacokinetics after nebulization among intubated patients.Critical care (London, England) · 2026Trial
- Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Single-center Randomized Controlled Trial.Chinese medical journal · 2017Trial
- Inhalable quercetin dihydrate nanosuspension mitigates silica-induced pulmonary fibrosis in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- How to Use Nebulized Antibiotics in Severe Respiratory Infections.Antibiotics (Basel, Switzerland) · 2023Review
- Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies.Frontiers in antibiotics · 2023Review
- The Unfulfilled Promise of Inhaled Therapy in Ventilator-Associated Infections: Where Do We Go from Here?Journal of aerosol medicine and pulmonary drug delivery · 2022Review
- Simultaneous Particle Size Reduction and Homogeneous Mixing to Produce Combinational Powder Formulations for Inhalation by the Single-Step Co-Jet Milling.Journal of pharmaceutical sciences · 2019Article
- Inhaled amikacin for severe Gram-negative pulmonary infections in the intensive care unit: current status and future prospects.Critical care (London, England) · 2018Review
- Composite particle formulations of colistin and meropenem with improved in-vitro bacterial killing and aerosolization for inhalation.International journal of pharmaceutics · 2018Article
- Review
- In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistantInfection and drug resistance · 2018Article
- Nebulized antibiotics in mechanically ventilated patients: a challenge for translational research from technology to clinical care.Annals of intensive care · 2017Review
- Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy.Antimicrobial agents and chemotherapy · 2017Article
- Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient.Annals of intensive care · 2016Review
- Inhaled Antibiotics for Gram-Negative Respiratory Infections.Clinical microbiology reviews · 2016Review
- Treatment of Gram-negative pneumonia in the critical care setting: is the beta-lactam antibiotic backbone broken beyond repair?Critical care (London, England) · 2016Article
- Clinical pharmacokinetics of inhaled antimicrobials.Clinical pharmacokinetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis 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).
methodsNine 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(®) 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.
resultsFifteen minutes after dosing with the 300/120 mg amikacin/fosfomycin combination, tracheal aspirate amikacin concentrations±SD were 12,390±3,986 μg/g, and fosfomycin concentrations were 6,174±2,548 μg/g (n=6). Airway clearance was rapid. Plasma concentrations were subtherapeutic; the highest observed amikacin plasma concentration was 1.4 μg/mL, and the highest observed fosfomycin plasma concentration was 0.8 μg/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.
conclusionsHigh 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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Registered trials
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