Macromolecular mechanisms of sputum inhibition of tobramycin activity
- 1 January 1995
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 39 (1) , 34-39
- https://doi.org/10.1128/aac.39.1.34
Abstract
Tobramycin, an aminoglycoside antibiotic, is used in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis patients. Tobramycin bioactivity, however, is antagonized by sputum. Glycoproteins (mucins) and high-molecular-weight DNA make up 2 to 3% (P. L. Masson and J. F. Heremans, p. 412-475, In M. J. Dulfano, ed., Sputum: Fundamentals and Clinical Pathology, 1973) and 3 to 10% (W. S. Chernick and G. J. Barbero, Pediatrics 24:739-745, 1959, and R. Picot, I. Das, and L. Reid, Thorax 33:235-242, 1978) of the dry weight of sputum, respectively. tobramycin binds to both mucins and DNA obtained from sputum (R. Ramphal, M. Lhermitte, M. Filliat, and P. Roussel, J. Antimicrob. Chemother. 22:483-490, 1988). In vitro, recombinant human DNase (rhDNase) hydrolyzes high-molecular-weight DNA of > 50 kb within sputum to fragments of 2 to 4 kb. Studying dialyzable tobramycin, we examined drug binding to whole sputum and to "mock sputum," which consisted of porcine gastric mucin and calf thymus DNA. We also studied the effects of rhDNase treatments of sputum, mock sputum, and calf thymus DNA on tobramycin binding. We found that treatments of sputum, mock sputum, and calf thymus DNA with rhDNase did not significantly increase the tobramycin bioactivity within the dialysates; surprisingly, sputum binding of tobramycin was increased by rhDNase. We conclude that rhDNase does not increase the bioactivity of tobramycin in sputum.Keywords
This publication has 20 references indexed in Scilit:
- The binding of anti-pseudomonal antibiotics to macromolecules from cystic fibrosis sputumJournal of Antimicrobial Chemotherapy, 1988
- Bioactivity of Gentamicin in Purulent Sputum from Patients with Cystic Fibrosis or Bronchiectasis: Comparison with Activity in SerumThe Journal of Infectious Diseases, 1983
- Gentamicin Inactivation in Purulent Exudates: Role of Cell LysisThe Journal of Infectious Diseases, 1980
- Pus, deoxyribonucleic acid, and sputum viscosity.Thorax, 1978
- Effect of Cation Content of Agar on the Activity of Gentamicin, Tobramycin, and Amikacin against Pseudomonas aeruginosaThe Journal of Infectious Diseases, 1978
- Role of Ionic Strength in Salt Antagonism of Aminoglycoside Action on Escherichia coli and Pseudomonas aeruginosaThe Journal of Infectious Diseases, 1976
- Interaction of Purulent Material with Antibiotics Used to Treat Pseudomonas InfectionsAntimicrobial Agents and Chemotherapy, 1974
- Antibiotic Susceptibility Testing of Pseudomonas aeruginosa: Selection of a Control Strain and Criteria for Magnesium and Calcium Content in MediaThe Journal of Infectious Diseases, 1974
- Relative Antagonism in vitro of Calcium in Serum to the Bactericidal Activities of Gentamicin and Tobramycin on Pseudomonas AeruginosaChemotherapy, 1973
- The differential attachment of antibiotics to glycoprotein and blood lymphocytesJournal of Clinical Pathology, 1970