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Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient.

Bassetti M, Luyt CE, Nicolau DP, Pugin J - Ann Intensive Care (2016)

Bottom Line: Gram-negative pneumonia in patients who are intubated and mechanically ventilated is associated with increased morbidity and mortality as well as higher healthcare costs compared with those who do not have the disease.Intravenous antibiotics are currently the standard of care for pneumonia; however, increasing rates of multidrug resistance and limited penetration of some classes of antimicrobials into the lungs reduce the effectiveness of this treatment option, and current clinical cure rates are variable, while recurrence rates remain high.Inhaled antibiotics may have the potential to improve outcomes in this patient population, but their use is currently restricted by a lack of specifically formulated solutions for inhalation and a limited number of devices designed for the nebulization of antibiotics.

View Article: PubMed Central - PubMed

Affiliation: Infectious Diseases Clinic, Santa Maria Misericordia University Hospital, Udine, Italy. mattba@tin.it.

ABSTRACT
Gram-negative pneumonia in patients who are intubated and mechanically ventilated is associated with increased morbidity and mortality as well as higher healthcare costs compared with those who do not have the disease. Intravenous antibiotics are currently the standard of care for pneumonia; however, increasing rates of multidrug resistance and limited penetration of some classes of antimicrobials into the lungs reduce the effectiveness of this treatment option, and current clinical cure rates are variable, while recurrence rates remain high. Inhaled antibiotics may have the potential to improve outcomes in this patient population, but their use is currently restricted by a lack of specifically formulated solutions for inhalation and a limited number of devices designed for the nebulization of antibiotics. In this article, we review the challenges clinicians face in the treatment of pneumonia and discuss the characteristics that would constitute an ideal inhaled drug/device combination. We also review inhaled antibiotic options currently in development for the treatment of pneumonia in patients who are intubated and mechanically ventilated.

No MeSH data available.


Related in: MedlinePlus

Relationship between aerodynamic diameter and site of lung deposition. The optimal particle size for deposition throughout the lung (total) is 3–5 µm.Adapted from Ref. [70]. Figure reproduced with permission, the publisher for this copyrighted material is Mary Ann Libert, Inc. publishers
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Fig3: Relationship between aerodynamic diameter and site of lung deposition. The optimal particle size for deposition throughout the lung (total) is 3–5 µm.Adapted from Ref. [70]. Figure reproduced with permission, the publisher for this copyrighted material is Mary Ann Libert, Inc. publishers

Mentions: For optimal therapeutic effect, an appropriately formulated antibiotic should be used in combination with an efficient delivery device. A recent meta-analysis of inhaled treatments showed that while nebulized antibiotics (with or without IV antibiotic) may improve clinical cure rates compared with IV antibiotics alone, nebulizers themselves vary considerably in efficiency [50]. Indeed, jet nebulizers are known to have considerably lower efficiency (i.e., drug delivery rates) than vibrating mesh nebulizers (<15 vs 40–60 %, respectively) [51]. However, even within the vibrating mesh nebulizer device category, there is significant variation in delivery efficiency (Table 1). One of the primary determinants of delivery efficiency and drug deposition is particle size; a consistent and optimal particle size promotes distribution throughout the lungs and avoids condensation (‘rain out’) within the ventilator circuit [27, 52]. Particle size is usually measured as mass median aerodynamic diameter (MMAD) or volumetric median diameter (VMD), and a particle size in the range of 1–5 µm is considered to be suitable for deposition in the lung [36]; within this range, an MMAD or VMD of 3–5 µm is considered optimal for deposition in the bronchial conducting airways and throughout the alveoli (Fig. 3). However, currently available jet nebulizers cannot produce such small particles [52].Table 1


Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient.

Bassetti M, Luyt CE, Nicolau DP, Pugin J - Ann Intensive Care (2016)

Relationship between aerodynamic diameter and site of lung deposition. The optimal particle size for deposition throughout the lung (total) is 3–5 µm.Adapted from Ref. [70]. Figure reproduced with permission, the publisher for this copyrighted material is Mary Ann Libert, Inc. publishers
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835402&req=5

Fig3: Relationship between aerodynamic diameter and site of lung deposition. The optimal particle size for deposition throughout the lung (total) is 3–5 µm.Adapted from Ref. [70]. Figure reproduced with permission, the publisher for this copyrighted material is Mary Ann Libert, Inc. publishers
Mentions: For optimal therapeutic effect, an appropriately formulated antibiotic should be used in combination with an efficient delivery device. A recent meta-analysis of inhaled treatments showed that while nebulized antibiotics (with or without IV antibiotic) may improve clinical cure rates compared with IV antibiotics alone, nebulizers themselves vary considerably in efficiency [50]. Indeed, jet nebulizers are known to have considerably lower efficiency (i.e., drug delivery rates) than vibrating mesh nebulizers (<15 vs 40–60 %, respectively) [51]. However, even within the vibrating mesh nebulizer device category, there is significant variation in delivery efficiency (Table 1). One of the primary determinants of delivery efficiency and drug deposition is particle size; a consistent and optimal particle size promotes distribution throughout the lungs and avoids condensation (‘rain out’) within the ventilator circuit [27, 52]. Particle size is usually measured as mass median aerodynamic diameter (MMAD) or volumetric median diameter (VMD), and a particle size in the range of 1–5 µm is considered to be suitable for deposition in the lung [36]; within this range, an MMAD or VMD of 3–5 µm is considered optimal for deposition in the bronchial conducting airways and throughout the alveoli (Fig. 3). However, currently available jet nebulizers cannot produce such small particles [52].Table 1

Bottom Line: Gram-negative pneumonia in patients who are intubated and mechanically ventilated is associated with increased morbidity and mortality as well as higher healthcare costs compared with those who do not have the disease.Intravenous antibiotics are currently the standard of care for pneumonia; however, increasing rates of multidrug resistance and limited penetration of some classes of antimicrobials into the lungs reduce the effectiveness of this treatment option, and current clinical cure rates are variable, while recurrence rates remain high.Inhaled antibiotics may have the potential to improve outcomes in this patient population, but their use is currently restricted by a lack of specifically formulated solutions for inhalation and a limited number of devices designed for the nebulization of antibiotics.

View Article: PubMed Central - PubMed

Affiliation: Infectious Diseases Clinic, Santa Maria Misericordia University Hospital, Udine, Italy. mattba@tin.it.

ABSTRACT
Gram-negative pneumonia in patients who are intubated and mechanically ventilated is associated with increased morbidity and mortality as well as higher healthcare costs compared with those who do not have the disease. Intravenous antibiotics are currently the standard of care for pneumonia; however, increasing rates of multidrug resistance and limited penetration of some classes of antimicrobials into the lungs reduce the effectiveness of this treatment option, and current clinical cure rates are variable, while recurrence rates remain high. Inhaled antibiotics may have the potential to improve outcomes in this patient population, but their use is currently restricted by a lack of specifically formulated solutions for inhalation and a limited number of devices designed for the nebulization of antibiotics. In this article, we review the challenges clinicians face in the treatment of pneumonia and discuss the characteristics that would constitute an ideal inhaled drug/device combination. We also review inhaled antibiotic options currently in development for the treatment of pneumonia in patients who are intubated and mechanically ventilated.

No MeSH data available.


Related in: MedlinePlus