Infection

, 37:424

Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients

  • J. Riethmueller
  • M. Ballmann
  • T. W. Schroeter
  • P. Franke
  • R. von Butler
  • A. Claass
  • S. Junge
  • G. Doering
  • M. Stern
  • German Multicenter Study Group
Clinical and Epidemiological Study

Abstract

Purpose:

We hypothesized that a single intravenous (iv) tobramycine infusion (treatment B) would have equivalent anti-infectious efficacy in chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) as the commonly performed treatment of three doses (treatment A) . Toxicity and practicability may even be improved in the single-dose regimen.

Methods:

This was a randomized crossover study comparing outcome after 14 and 35 days. The primary end-point was a decrease in the leukocyte count, and the secondary end-points were clinical and lung function parameters, Pseudomonas quantification in sputum, and inflammation markers (immunoglobulin G, C-reactive protein) in serum. 30 patients (20 female, mean age 11.2 years, mean age range 1.7–18.1 years) received elective 14-day courses of treatments A or B, followed by the alternative treatment after a mean interval of 37 (± 21) weeks.

Results:

With the exception of PA density, there were no significant differences between both treatment strategies after 14 days of treatment. After 35 days of treatment, there were no significant changes in the leukocyte count and inflammation markers. Both treatment strategies reduced the bacterial load in the airways, as reflected by a decreased PA density in sputum. Nephrotoxicity was equal in both groups, with a transient slight elevation of urinary N-acetyl-β-glucosaminidase concentrations. Standard audiometry tests revealed no evidence of a hearing impairment in any patient following therapy. Mean body weight increased during the study period by 0.5 kg. Forced expiratory volume increased by approximately 5% of the predicted volume, forced vital capacity increased by 2% of predicted capacity, and forced mid expiratory flow rate increased by 7% (A) or 4% (B) of the predicted normal value, although these changes were not statistically significant.

Conclusion:

We conclude that tobramycin given in a daily single dose (with the advantage of being more practical in a home environment) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinically stable patients with CF.

References

  1. 1.
    Schaedel C, de Monestrol I, Hjelte L, Johannesson M, Kornfält R, Lindblad A, Strandvik B, Wahlgren L, Holmberg L: Predictors of deterioration of lung function in cystic fibrosis. Pediatr Pulmonol. Pediatr Pulmonol 2002; 33: 483–491.Google Scholar
  2. 2.
    Schoeni MH, Casaulta-Aebischer C: Nutrition and lung function in cystic fibrosis patients: review. Clin Nutr 2000; 19: 79–85.CrossRefGoogle Scholar
  3. 3.
    Steinkamp G, Wiedemann B: Relationship between nutritional status and lung function in cystic fibrosis: cross sectional and longitudinal analyses from the German CF quality assurance (CFQA) project. Thorax 2002; 57: 596–601.CrossRefPubMedGoogle Scholar
  4. 4.
    Doering G, Conway SP, Heijerman HG, Hodson ME, Hoiby N, Smyth A, Touw DJ: Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 2000; 16: 749–767.CrossRefGoogle Scholar
  5. 5.
    Stern M, Sens B, Wiedemann B, Busse O, Wenzlaff P: Qualitätssicherung Mukoviszidose 2002. Überblick über den Gesundheitszustand der Patienten in Deutschland. Zentrum für Qualitätsmanagement im Gesundheitswesen. Einrichtung der Ärztekammer: Niedersachsen, 2003.Google Scholar
  6. 6.
    Høiby N: Prospects for the prevention and control of pseudomonal infection in children with cystic fibrosis. Paediatr Drugs 2000; 2: 451–463.CrossRefPubMedGoogle Scholar
  7. 7.
    Elborn JS, Prescott RJ, Stack BH, Goodchild MC, Bates J, Pantin C, Ali N, Shale DJ, Crane M: Elective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs. Thorax 2000; 55: 355–358.CrossRefPubMedGoogle Scholar
  8. 8.
    Breen L, Aswani N: Elective versus symptomatic intravenous antibiotic therapy for cystic fibrosis. Cochrane Database Syst Rev 2001; 4: CD002767. doi: 10.1002/14651858.CD002767.PubMedGoogle Scholar
  9. 9.
    Marco T, Asensio O, Bosque M, de Gracia J, Serra C: Home intravenous antibiotics for cystic fibrosis. Cochrane Database Syst Rev 2000; 4: CD001917.PubMedGoogle Scholar
  10. 10.
    Riethmueller J, Busch A, Damm V, Ziebach R, Stern M: Home and hospital antibiotic treatment prove similarly effective in cystic fibrosis. Infection 2002; 30: 387–391.CrossRefPubMedGoogle Scholar
  11. 11.
    Barza M, Ioannidis JP, Cappelleri JC, Lau J: Single or multiple daily doses of aminoglycosides: a meta-analysis. Br Med J 1996; 312: 338–345.Google Scholar
  12. 12.
    Bates RD, Nahata MC, Jones JW, McCoy K, Young G, Cox S, Barson WJ: Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis. Chest 1997; 112: 1208–1213.CrossRefPubMedGoogle Scholar
  13. 13.
    Heininger U, Boewing B, Stehr K, Solbach W: [Aminoglycosides in patients with mucoviscidosis and pulmonary exacerbation: comparison of once or three times daily administration] TT-Aminoglykoside bei Patienten mit Mukoviszidose und pulmonaler Exazerbation: Vergleich von Einmal- und Dreimalgabe. Klin Paediatr 1993; 205: 18–22.CrossRefGoogle Scholar
  14. 14.
    Vic P, Ategbo S, Turck D, Husson MO, Launay V, Loeuille GA, Sardet A, Deschildre A, Druon D, Arrouet-Lagande C: Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for Pseudomonas exacerbations in cystic fibrosis. Arch Dis Child 1998; 78: 536–539.CrossRefPubMedGoogle Scholar
  15. 15.
    Whitehead A, Conway SP, Etherington C, Caldwell NA, Setchfield N, Bogle S: Once-daily tobramycin in the treatment of adult patients with cystic fibrosis. Eur Respir J 2002; 19: 303–309.CrossRefPubMedGoogle Scholar
  16. 16.
    Smyth A, Tan KH, Hyman-Taylor P, Mulheran M, Lewis S, Stableforth D, Knox A, Group TS: Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis-the TOPIC study: a randomised controlled trial. Lancet 2005; 365: 573–578.PubMedGoogle Scholar
  17. 17.
    Doering G, Obernesser HJ, Botzenhart K, Flehmig B, Hoiby N, Hofmann A: Proteases of Pseudomonas aeruginosa in patients with cystic fibrosis. J Infect Dis 1983; 147: 744–750.Google Scholar
  18. 18.
    Bauernfeind A, Bertele RM, Harms K, Horl G, Jungwirth K, Petermueller C, Przyklenk B, Weisslein-Pfister C: Qualitative and quantitative microbiological analysis of sputa of 102 patients with cystic fibrosis. Infection 1987; 15: 270–277.CrossRefPubMedGoogle Scholar
  19. 19.
    Hoppe JE, Theurer-Mainka U, Stern M: Comparison of three methods for culturing throat swabs from cystic fibrosis patients. J Clin Microbiol 1995; 33: 1896–1898.PubMedGoogle Scholar
  20. 20.
    Quanjer PH: Standardized lung function testing: report working Party “standardization of lung function tests”, European Community for Coal and Steel. Bull Eur Physiopathol Respir 1983; 19: 1–95.Google Scholar
  21. 21.
    Zapletal A, Samanek M, Paul T: Lung function in children and adolescents. methods, reference values. Karger, Basel, 1987.Google Scholar
  22. 22.
    Cunningham S, McColm JR, Mallinson A, Boyd I, Marshall TG: Duration of effect of intravenous antibiotics on spirometry and sputum cytokines in children with cystic fibrosis. Pediatr Pulmonol 2003; 36: 43–48.CrossRefPubMedGoogle Scholar
  23. 23.
    Glass S, Plant ND, Spencer DA: The effects of intravenous tobramycin on renal tubular function in children with cystic fibrosis. J Cyst Fibros 2005; 4: 221–225.CrossRefPubMedGoogle Scholar
  24. 24.
    Ambrose PG, Bhavnani SM, Rubino CM, Louie A, Gumbo T, Forrest A, Drusano GL: Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it’s not just for mice anymore. Clin Infect Dis 2007; 44: 79–86.CrossRefPubMedGoogle Scholar
  25. 25.
    Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, Ioannidis JP: Extended-interval aminoglycoside administration for children: a meta-analysis. Pediatrics 2004; 114: e111–e118.CrossRefPubMedGoogle Scholar
  26. 26.
    Tan K, Bunn H: Once daily versus multiple daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev 2000; 4: CD002009.PubMedGoogle Scholar
  27. 27.
    Beringer PM, Vinks AA, Jelliffe RW, Shapiro BJ: Pharmacokinetics of tobramycin in adults with cystic fibrosis: implications for once-daily administration. Antimicrob Agents Chemother 2000; 44: 809–813.CrossRefPubMedGoogle Scholar
  28. 28.
    Moore RD, Smith CR, Lietman PS: The association of aminoglycoside plasma levels with mortality in patients with Gramnegative bacteremia. J Infect Dis 1984; 149: 443–448.PubMedGoogle Scholar
  29. 29.
    Shawar RM, MacLeod DL, Garber RL, Burns JL, Stapp JR Clausen CR, Tanaka SK: Activities of tobramycin and six other antibiotics against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 1999; 43: 2877–2880.PubMedGoogle Scholar
  30. 30.
    Aminimanizani A, Beringer PM, Kang J, Tsang L, Jelliffe RW, Shapiro BJ: Distribution and elimination of tobramycin administered in single or multiple daily doses in adult patients with cystic fibrosis. J Antimicrob Chemother 2002; 50: 553–559.CrossRefPubMedGoogle Scholar
  31. 31.
    Bartel K, Habash T, Lugauer S, Barmeier H, Bowing B, Unsal M, Schoerner C, Heininger U: Optimal tobramycin dosage in patients with cystic fibrosis-evidence for predictability based on previous drug monitoring. Infection 1999; 27: 268–271.CrossRefPubMedGoogle Scholar
  32. 32.
    Bragonier R, Brown NM: The pharmacokinetics and toxicity of once-daily tobramycin therapy in children with cystic fibrosis. J Antimicrob Chemother 1998; 42: 103–106.CrossRefPubMedGoogle Scholar
  33. 33.
    Vogelman B, Gudmundsson S, Turnidge J, Leggett J, Craig WA: In vivo postantibiotic effect in a thigh infection in neutropenic mice. J Infect Dis 1988; 157: 287–298.PubMedGoogle Scholar
  34. 34.
    Kumar A, Hay MB, Maier GA, Dyke JW: Post-antibiotic effect of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin for Pseudomonas cepacia. J Antimicrob Chemother 1992; 30: 597–602.CrossRefPubMedGoogle Scholar
  35. 35.
    Steinkamp G, Lutge M, Wurster U, Schulz-Baldes JG, Grone HJ, Ehrich JH: Renal function in cystic fibrosis: proteinuria and enzymuria before and after tobramycin therapy. Eur J Pediatr 1986; 145: 526–531.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • J. Riethmueller
    • 1
  • M. Ballmann
    • 3
  • T. W. Schroeter
    • 2
  • P. Franke
    • 1
  • R. von Butler
    • 1
  • A. Claass
    • 2
  • S. Junge
    • 3
  • G. Doering
    • 4
  • M. Stern
    • 1
  • German Multicenter Study Group
  1. 1.University Children’s HospitalTübingenGermany
  2. 2.University Children’s Hospital KielKielGermany
  3. 3.Pediatric Dept.University of HannoverHannoverGermany
  4. 4.Hygiene-Institut, University of TübingenTübingenGermany

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