Quantitative Deposition of Aerosolized Gentamicin in Cystic Fibrosis

Abstract

In cystic fibrosis (CF), the clinical effectiveness of aerosolized antibiotics is controversial. Previous investigators have not considered the type of nebulizer, droplet size, and dose to the lung in assessing the results of aerosol therapy. The present study tests the importance of these factors by standardizing an aerosol system for delivery of antibiotics and other agents to patients with CF. Particle size, distribution, and output from a commercially available nebulizer were measured. Thirteen patients with CF inhaled aerosol (MMAD = 1.1 micron) containing gentamicin (160 mg in nebulizer) and 99mTc-labeled human serum albumin. Patients' sputum and serum were analyzed for gentamicin levels by immunoenzymatic assay (Emit; Syva Corp., Palo Alto, CA). Using a gamma camera and suitable filters, central versus peripheral deposition (C/P ratio) and whole lung deposition were measured and related to sputum gentamicin levels. Gentamicin deposit averaged 12.3 mg +/- 5.9 (SD) or 7.69% of the original amount placed in the nebulizer. Peak sputum levels averaged 376.6 micrograms/ml +/- 275, whereas serum levels were undetectable in all patients. When peak sputum levels were normalized for the amount deposited, a close correlation with C/P ratio was obtained (r = 0.88, p less than 0.05). Furthermore, an inverse relationship was found between the C/P ratio and the %FEV1 (r = 0.76, p less than 0.05). Finally, a bell-shaped relationship between deposited dose and minute ventilation was seen in the patients (r = 0.88, p less than 0.05), i.e., an optimal minute ventilation was shown. These relationships may be important when designing future clinical studies.

Lung deposition from the Turbuhaler in children with cystic fibrosis

“…Previous deposition studies [25] and theoretical models of deposition [27] suggest that there is a trend for increased deposition in larger central airways as age decreases. However the pattern of deposition of aerosols is very sensitive to airways obstruction and, indeed, can detect progressive obstructive airways disease long before changes in lung function become apparent [28,29]. The older subjects with CF are likely to have more significant disease than the younger subjects, hence encouraging more central deposition and obscuring any trend with age due to changes in anatomy.…”

Pulmonary Administration of Gentamicin During Liquid Ventilation in a Newborn Lamb Lung Injury Model

“…A prevailing problem when evaluating the usefulness of aerosol therapy is the estimation of the dose of medication actually delivered to the patient's lungs, which depends on many variables including nebulizer type and output, particle size, and patient breathing pattern. 10,32,33 In addition, the presence of uneven distribution of ventilation attributable to severe airway obstruction or mucus hypersecretion can further limit the usefulness of aerosols and prevent them from reaching the appropriate receptor sites in the lung. 9 Poor peripheral lung delivery with aerosolization is reflected in very low serum aminoglycoside levels.…”

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

“…In general, large differences were found in relation to these variables [162, 166, 167, 171± 173]. For instance, deposition of aerosols in the airways may differ between the nebulizers as shown in radioaerosol studies [163,167,169]. In one study, a mean of 7% of inhaled tobramycin dose reached the lungs, while only 16% of this pulmonary tobramycin was deposited peripherally.…”

“…The greater the lung damage as indicated by FEV1 and Chrispin-Norman score, the smaller the proportion of pulmonary tobramycin that reached the periphery [165]. [163]. In general, the distribution of a drug in the CF lung is not homogenous, but focal in the larger central lung areas [164,174,175].…”