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. 1998 Jun;78(6):536–539. doi: 10.1136/adc.78.6.536

Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis

P Vic 1, S Ategbo 1, D Turck 1, M Husson 1, V Launay 1, G Loeuille 1, A Sardet 1, A Deschildre 1, D Druon 1, C Arrouet-Lagande 1
PMCID: PMC1717599  PMID: 9713009

Abstract

OBJECTIVE—To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis.
DESIGN—22 patients with cystic fibrosis, mean (SD) age 11 (3.4) years (range 5.6-19.3), with pulmonary pseudomonas exacerbations were randomly assigned to receive a 14 day course of tobramycin (15 mg/kg/day) either in three infusions (group A) (n = 10) or a single daily infusion (group B) (n = 12), combined with ceftazidime (200 mg/kg/day as three intravenous injections). Efficacy was assessed by comparison of pulmonary, nutritional, and inflammatory indices on days 1 and 14. Cochlear and renal tolerance were assessed on days 1 and 14. Tobramycin concentration was measured in serum and sputum 1, 2, 3, 4, 8, and 24 hours after the start of the infusion. Analysis was by non-parametric Wilcoxon test.
RESULTS—Variables improving (p < 0.05) in both groups A and B were, respectively: weight/height (+4% and +3.1%), plasma prealbumin (+66 and +63 mg/l), forced vital capacity (FVC) (+14% and +11%), forced expiratory volume in one second (+15% and +14%), and forced expiratory flow between 25% and 75% of FVC (+13% and +21%). Improvement was not significantly different between groups. Renal and cochlear indices remained within the normal range. Serum peak concentration of tobramycin on day 1 was 13.2 (7.1) mg/l in group A and 42.5 (11.2) mg/l in group B (p < 0.001); serum trough was 1.1 (0.8) mg/l in group A and 0.3 (0.2) mg/l in group B (p < 0.01). Tobramycin concentrations in sputum were two to three times higher in group B than group A.
CONCLUSIONS—Once daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients. 



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Selected References

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  1. David T. J. Cystic fibrosis. Arch Dis Child. 1990 Jan;65(1):152–157. doi: 10.1136/adc.65.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. De Broe M. E., Verbist L., Verpooten G. A. Influence of dosage schedule on renal cortical accumulation of amikacin and tobramycin in man. J Antimicrob Chemother. 1991 May;27 (Suppl 100):41–47. doi: 10.1093/jac/27.suppl_c.41. [DOI] [PubMed] [Google Scholar]
  3. Gilbert D. N. Once-daily aminoglycoside therapy. Antimicrob Agents Chemother. 1991 Mar;35(3):399–405. doi: 10.1128/aac.35.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guglielmo B. J., Quan L. A., Stulbarg M. S. Pharmacokinetics of once-daily versus thrice daily tobramycin in cystic fibrosis patients. J Antimicrob Chemother. 1996 May;37(5):1040–1042. doi: 10.1093/jac/37.5.1040. [DOI] [PubMed] [Google Scholar]
  5. Kovarik J. M., Hoepelman I. M., Verhoef J. Once-daily aminoglycoside administration: new strategies for an old drug. Eur J Clin Microbiol Infect Dis. 1989 Sep;8(9):761–769. doi: 10.1007/BF02185842. [DOI] [PubMed] [Google Scholar]
  6. Levy J., Smith A. L., Koup J. R., Williams-Warren J., Ramsey B. Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study. J Pediatr. 1984 Jul;105(1):117–124. doi: 10.1016/s0022-3476(84)80375-3. [DOI] [PubMed] [Google Scholar]
  7. Lindsay C. A., Bosso J. A. Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations. Clin Pharmacokinet. 1993 Jun;24(6):496–506. doi: 10.2165/00003088-199324060-00005. [DOI] [PubMed] [Google Scholar]
  8. Moore R. D., Lietman P. S., Smith C. R. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987 Jan;155(1):93–99. doi: 10.1093/infdis/155.1.93. [DOI] [PubMed] [Google Scholar]
  9. Neijens H. J. Strategies and perspectives in treatment of respiratory infections. Acta Paediatr Scand Suppl. 1989;363:66–73. doi: 10.1111/apa.1989.78.s363.66. [DOI] [PubMed] [Google Scholar]
  10. Nelson J. D. Management of acute pulmonary exacerbations in cystic fibrosis: a critical appraisal. J Pediatr. 1985 Jun;106(6):1030–1034. doi: 10.1016/s0022-3476(85)80264-x. [DOI] [PubMed] [Google Scholar]
  11. Nordström L., Lerner S. A. Single daily dose therapy with aminoglycosides. J Hosp Infect. 1991 Jun;18 (Suppl A):117–129. doi: 10.1016/0195-6701(91)90013-x. [DOI] [PubMed] [Google Scholar]
  12. Pechère J. C., Craig W. A., Meunier F. Once daily dosing of aminoglycoside: one step forward. J Antimicrob Chemother. 1991 May;27 (Suppl 100):149–152. doi: 10.1093/jac/27.suppl_c.149. [DOI] [PubMed] [Google Scholar]
  13. Smith A. L. Antibiotic therapy in cystic fibrosis: evaluation of clinical trials. J Pediatr. 1986 May;108(5 Pt 2):866–870. doi: 10.1016/s0022-3476(86)80759-4. [DOI] [PubMed] [Google Scholar]
  14. Smith A. L., Ramsey B., Redding G., Haas J. Endobronchial infection in cystic fibrosis. Acta Paediatr Scand Suppl. 1989;363:31–36. doi: 10.1111/apa.1989.78.s363.31. [DOI] [PubMed] [Google Scholar]
  15. Strandvik B., Hjelte L., Malmborg A. S., Widén B. Home intravenous antibiotic treatment of patients with cystic fibrosis. Acta Paediatr. 1992 Apr;81(4):340–344. doi: 10.1111/j.1651-2227.1992.tb12239.x. [DOI] [PubMed] [Google Scholar]
  16. Szaff M., Høiby N., Flensborg E. W. Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand. 1983 Sep;72(5):651–657. doi: 10.1111/j.1651-2227.1983.tb09789.x. [DOI] [PubMed] [Google Scholar]
  17. Van der Auwera P. Pharmacokinetic evaluation of single daily dose amikacin. J Antimicrob Chemother. 1991 May;27 (Suppl 100):63–71. doi: 10.1093/jac/27.suppl_c.63. [DOI] [PubMed] [Google Scholar]
  18. Vic P., Ategbo S., Turck D., Husson M. O., Tassin E., Loeuille G. A., Deschildre A., Druon D., Elian J. C., Arrouet-Lagandre C. Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients. Eur J Pediatr. 1996 Nov;155(11):948–953. doi: 10.1007/BF02282885. [DOI] [PubMed] [Google Scholar]
  19. van Aalderen W. M., Mannes G. P., Bosma E. S., Roorda R. J., Heymans H. S. Home care in cystic fibrosis patients. Eur Respir J. 1995 Jan;8(1):172–175. doi: 10.1183/09031936.95.08010172. [DOI] [PubMed] [Google Scholar]

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