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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

Ideal properties of an antibiotic solution for aerosolization.Adapted from information in references [26, 27, 29]
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Fig2: Ideal properties of an antibiotic solution for aerosolization.Adapted from information in references [26, 27, 29]

Mentions: Currently available IV drug formulations are not optimized for aerosolization and often have properties that may impede drug delivery [26]. In addition, IV formulations usually contain preservatives such as phenols and many have sub-optimal osmolarity (<150 mOsm/L, >1200 mOsm/L), which can increase bronchospasm and coughing [26, 27]. To be suitable for aerosolization, the formulation should be sterile, preservative-free and non-pyrogenic. It should also be adjusted for the lung environment with a suitable pH (4.0–8.0), osmolarity (150–1200 mOsm/L) and tonicity [26, 27, 29] (Fig. 2). A solution that is specifically formulated for inhalation could minimize adverse effects, such as airway irritation, and increase delivery efficiency. Currently, the only antimicrobials that have a specific formulation developed for inhalation are colistin [45], aztreonam [46] and tobramycin [47], all of which are approved exclusively for use in cystic fibrosis [48].Fig. 2


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)

Ideal properties of an antibiotic solution for aerosolization.Adapted from information in references [26, 27, 29]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Ideal properties of an antibiotic solution for aerosolization.Adapted from information in references [26, 27, 29]
Mentions: Currently available IV drug formulations are not optimized for aerosolization and often have properties that may impede drug delivery [26]. In addition, IV formulations usually contain preservatives such as phenols and many have sub-optimal osmolarity (<150 mOsm/L, >1200 mOsm/L), which can increase bronchospasm and coughing [26, 27]. To be suitable for aerosolization, the formulation should be sterile, preservative-free and non-pyrogenic. It should also be adjusted for the lung environment with a suitable pH (4.0–8.0), osmolarity (150–1200 mOsm/L) and tonicity [26, 27, 29] (Fig. 2). A solution that is specifically formulated for inhalation could minimize adverse effects, such as airway irritation, and increase delivery efficiency. Currently, the only antimicrobials that have a specific formulation developed for inhalation are colistin [45], aztreonam [46] and tobramycin [47], all of which are approved exclusively for use in cystic fibrosis [48].Fig. 2

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