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Aerosolized antibiotics: do they add to the treatment of pneumonia?

Kollef MH, Hamilton CW, Montgomery AB - Curr. Opin. Infect. Dis. (2013)

Bottom Line: The increasing rate of ventilator-associated pneumonia (VAP) caused by multidrug-resistant pathogens warrants the development of new treatment strategies.Recent studies indicate that aerosolized delivery systems for specially formulated antibiotics yield high local concentrations with rapid clearance and low systemic exposure.No single aerosolized antibiotic is likely to provide broad-spectrum activity against both Gram-negative and Gram-positive bacteria.

View Article: PubMed Central - PubMed

Affiliation: aVirginia E. and Sam J. Golman Chair in Respiratory Intensive Care Medicine, Washington University School of Medicine, St. Louis, Missouri bVirginia Commonwealth University School of Pharmacy, Richmond cPrincipal, Hamilton House, Virginia Beach, Virginia dCardeas Pharma Corp., Seattle, Washington, USA.

ABSTRACT

Purpose of review: The increasing rate of ventilator-associated pneumonia (VAP) caused by multidrug-resistant pathogens warrants the development of new treatment strategies. Carefully engineered delivery systems are undergoing evaluation to test the hypothesis that aerosolized administration of antibiotics will provide high local concentrations and fast clearance, which in turn may improve efficacy and decrease the risk of microbial resistance.

Recent findings: Recent studies indicate that aerosolized delivery systems for specially formulated antibiotics yield high local concentrations with rapid clearance and low systemic exposure. Preliminary clinical studies reveal that aerosolized delivery of antibiotics is well tolerated and active, when combined with intravenous antibiotics. No single aerosolized antibiotic is likely to provide broad-spectrum activity against both Gram-negative and Gram-positive bacteria.

Summary: Large multicenter trials are needed to determine whether preliminary findings will translate to improved clinical activity and decreased microbial resistance in VAP patients, and to optimize the use of aerosolized antibiotics.

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Related in: MedlinePlus

Peak amikacin concentrations in tracheal aspirates after aerosolized amikacin 50 mg/ml (with fosfomycin 20 mg/ml) by PARI Investigational eFlow Inline Nebulizer System in a phase 1, dose-escalation trial of seven patients with ventilator-associated pneumonia [26]. The breakpoint for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. is 16 μg/ml. SD, standard deviation.
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Figure 1: Peak amikacin concentrations in tracheal aspirates after aerosolized amikacin 50 mg/ml (with fosfomycin 20 mg/ml) by PARI Investigational eFlow Inline Nebulizer System in a phase 1, dose-escalation trial of seven patients with ventilator-associated pneumonia [26]. The breakpoint for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. is 16 μg/ml. SD, standard deviation.

Mentions: The author (A.B.M.) and colleagues [26] observed high sputum (and low systemic) concentrations after amikacin and fosfomycin by PARI nebulizer in patients with VAP or ventilator-associated tracheobronchitis in a double-blind, randomized, phase 1 trial. Each patient received three escalating doses of amikacin 50 mg/ml and fosfomycin 20 mg/ml at 24-h intervals. On day 3, patients were randomly assigned to two doses of amikacin and fosfomycin or placebo at 2-h intervals. Initial results in the first seven patients at 15 min after dosing revealed that amikacin concentrations in tracheal aspirates were more than or equal to 178-fold higher than the MIC90 of 16 μg/ml for Enterobacteriaceae, P. aeruginosa, and Acinetobacter spp. in a recent trial [34]; mean levels after the 6-ml dose were greater than or equal to 800-fold higher (Fig. 1). Fosfomycin concentrations were greater than or equal to 54-fold higher than the MIC90 of 32 μg/ml for MRSA isolates [35]; mean levels after the 6-ml dose were greater than or equal to 281-fold higher (Fig. 2). Plasma concentrations were more than 2000-fold lower; the highest were 1.4 μg/ml for amikacin and 0.8 μg/ml for fosfomycin [26].


Aerosolized antibiotics: do they add to the treatment of pneumonia?

Kollef MH, Hamilton CW, Montgomery AB - Curr. Opin. Infect. Dis. (2013)

Peak amikacin concentrations in tracheal aspirates after aerosolized amikacin 50 mg/ml (with fosfomycin 20 mg/ml) by PARI Investigational eFlow Inline Nebulizer System in a phase 1, dose-escalation trial of seven patients with ventilator-associated pneumonia [26]. The breakpoint for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. is 16 μg/ml. SD, standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814630&req=5

Figure 1: Peak amikacin concentrations in tracheal aspirates after aerosolized amikacin 50 mg/ml (with fosfomycin 20 mg/ml) by PARI Investigational eFlow Inline Nebulizer System in a phase 1, dose-escalation trial of seven patients with ventilator-associated pneumonia [26]. The breakpoint for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. is 16 μg/ml. SD, standard deviation.
Mentions: The author (A.B.M.) and colleagues [26] observed high sputum (and low systemic) concentrations after amikacin and fosfomycin by PARI nebulizer in patients with VAP or ventilator-associated tracheobronchitis in a double-blind, randomized, phase 1 trial. Each patient received three escalating doses of amikacin 50 mg/ml and fosfomycin 20 mg/ml at 24-h intervals. On day 3, patients were randomly assigned to two doses of amikacin and fosfomycin or placebo at 2-h intervals. Initial results in the first seven patients at 15 min after dosing revealed that amikacin concentrations in tracheal aspirates were more than or equal to 178-fold higher than the MIC90 of 16 μg/ml for Enterobacteriaceae, P. aeruginosa, and Acinetobacter spp. in a recent trial [34]; mean levels after the 6-ml dose were greater than or equal to 800-fold higher (Fig. 1). Fosfomycin concentrations were greater than or equal to 54-fold higher than the MIC90 of 32 μg/ml for MRSA isolates [35]; mean levels after the 6-ml dose were greater than or equal to 281-fold higher (Fig. 2). Plasma concentrations were more than 2000-fold lower; the highest were 1.4 μg/ml for amikacin and 0.8 μg/ml for fosfomycin [26].

Bottom Line: The increasing rate of ventilator-associated pneumonia (VAP) caused by multidrug-resistant pathogens warrants the development of new treatment strategies.Recent studies indicate that aerosolized delivery systems for specially formulated antibiotics yield high local concentrations with rapid clearance and low systemic exposure.No single aerosolized antibiotic is likely to provide broad-spectrum activity against both Gram-negative and Gram-positive bacteria.

View Article: PubMed Central - PubMed

Affiliation: aVirginia E. and Sam J. Golman Chair in Respiratory Intensive Care Medicine, Washington University School of Medicine, St. Louis, Missouri bVirginia Commonwealth University School of Pharmacy, Richmond cPrincipal, Hamilton House, Virginia Beach, Virginia dCardeas Pharma Corp., Seattle, Washington, USA.

ABSTRACT

Purpose of review: The increasing rate of ventilator-associated pneumonia (VAP) caused by multidrug-resistant pathogens warrants the development of new treatment strategies. Carefully engineered delivery systems are undergoing evaluation to test the hypothesis that aerosolized administration of antibiotics will provide high local concentrations and fast clearance, which in turn may improve efficacy and decrease the risk of microbial resistance.

Recent findings: Recent studies indicate that aerosolized delivery systems for specially formulated antibiotics yield high local concentrations with rapid clearance and low systemic exposure. Preliminary clinical studies reveal that aerosolized delivery of antibiotics is well tolerated and active, when combined with intravenous antibiotics. No single aerosolized antibiotic is likely to provide broad-spectrum activity against both Gram-negative and Gram-positive bacteria.

Summary: Large multicenter trials are needed to determine whether preliminary findings will translate to improved clinical activity and decreased microbial resistance in VAP patients, and to optimize the use of aerosolized antibiotics.

Show MeSH
Related in: MedlinePlus