Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Rationale for Aerosolized Antibiotic Dosage
Rationale for Aerosolized Antibiotic Dosage
Various factors, including sputum penetration, sputum components such as glycoproteins that antagonize antibiotic bioactivity, and the patient-to-patient differences in glycoprotein concentration, impact on the activity of antibiotics within the lung. These factors make estimating dosages difficult and are summarized below. asthma inhaler
Sputum Penetration of IV Administered Antibiotics Is Poor: Studies with (3-lactam agents have indicated that at most, 10 to 20% of the maximum serum concentration can be quantitated in the sputum. Virtually all these studies have used bioassays that may not detect antagonism of (3-lactam action by sputum components.
Aminoglycosides have variable penetration into CF sputum. Data suggest that the maximal sputum concentration following IV administration is often below and rarely exceeds the MIC* for P aeruginosa when studied in vitro.
Sputum Components Antagonize the Bioactivity ofAminoglycosides: The sputum from CF patients is known to antagonize antibiotic activity. There appear to be two classes of antagonistic components in sputum: small molecules adversely affect the penetration of the antibiotic into the bacterium and large molecules sequester the aminoglycoside through binding. This binding is almost exclusively due to sputum mucins (95%), since removing DNA in sputum by DNase does not affect activity. Soluble components in sputum, such as monovalent and divalent cations, which can also antagonize the bioactivity of aminoglycosides, vary little from patient to patient.
Glycoprotein Concentration Varies Among CF Patients: Due to variability in the degree of puru-lence, there is a wide range in the concentration of sputum glycoproteins (ie, mucins and DNA) among CF patients. The average sputum glycoprotein content is 60 mg/g but can be as high as 155 mg/g. Thus, the amount of tobramycin that needs to be deposited in the lower respiratory tract to achieve a bactericidal concentration can vary substantially from patient to patient.