The interaction of five anti-pseudomonas antibiotics with both commercial and pseudomonas alginates was studied by investigation of their binding and diffusion characteristics. The two sources of alginate were qualitatively but not quantitatively similar in these respects. Unlike the beta-lactams, gentamicin and tobramycin bound avidly to both sources of alginate and, when the alginate gel to antibiotic ratio was high, the aminoglycosides exhibited diffusion coefficients which were approximately 20% of the beta-lactam values. At much lower ratios of alginate to antibiotic the aminoglycosides caused precipitation in the alginate with apparent disruption of the gel structure, and ultimately penetrated the gel at a faster rate than the beta-lactams. The strong aminoglycoside binding to alginate was reduced, but not eliminated by the presence of physiological concentrations of salts.

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Background -Viscoelastic secretions in cystic fibrosis cause impaired mucus clearance and persistence of bacteria within the lung. The abnormal rheology is partly due to the presence of high molecular weight deoxyribonucleic acid (DNA). Recombinant human DNase I (rhDNase) has been shown to depolymerise DNA and thereby reduce the in vitro viscoelasticity of sputum in patients with cystic fibrosis. A phase II double blind placebo controlled study showed that rhDNase improved pulmonary function in patients with cystic fibrosis. The object of the present study was to evaluate the in vivo effects of rhDNase on sputum rheology and to determine whether these were correlated with changes in pulmonary function. Methods -Patients were randomised to receive either placebo or rhDNase 2-5 mg twice daily for 10 days. Sputum samples were collected in sterile containers during screening and during treatment with the study drug. Pulmonary function and rheological analysis were the primary outcomes evaluated. Other parameters assessed were quantitative sputum bacteriology, sputum DNA concentration, and change in molecular mass of DNA polymers.Results -The viscoelasticity of the sputum in untreated patients with cystic fibrosis was high and treatment with rhDNase reduced all the rheological parameters measured: dynamic storage modulus (a measure of elasticity), dynamic loss modulus (a measure ofviscosity), and log complex modulus (a measure of mucus rigidity). The calculated cough clearance index was also improved following treatment with rhDNase. These rheological parameters showed a correlation with forced expiratory volume in one second (FEV1) which was improved by a mean (SE) of 13'3 (5-6)% on day 10 of treatment with rhDNase compared with a change of 0-2 (3.1)% in the placebo group. There was no change in bacterial colony counts or sputum DNA concentrations following treatment with rhDNase, but a small decrease in high molecular weight DNA was observed. Conclusions -Patients with cystic fibrosis treated with rhDNase show an improvement in rheological properties and pulmonary function, one of the mechanisms being a reduction in the proportion of high molecular weight DNA.

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