, 189:409 | Cite as

Improved Outcomes of Patients with End-stage Cystic Fibrosis Requiring Invasive Mechanical Ventilation for Acute Respiratory Failure

  • Don HayesJr.Email author
  • Heidi M. Mansour


Study Objectives

The aim of this study was to determine the effects of an antibiotic strategy with intravenous (IV) continuous infusion of a β-lactam (CIBL) antibiotic and high-dose extended-interval (HDEI) tobramycin upon outcomes in patients with cystic fibrosis (CF) requiring invasive mechanical ventilation (IMV) for acute respiratory failure.


The study was a retrospective review from June 1, 2006, to December 1, 2010, of patients at a university hospital with an adult CF center.


The study population included adult CF patients requiring IMV. A total of 15 hospitalizations with IMV episodes were reviewed, involving 10 adult (31.4 ± 11.1 years) CF patients with end-stage lung disease (FEV1 = 23.6 ± 7.8% predicted) and malnutrition (body mass index = 20.5 ± 3.1). Each patient survived to discharge and to follow-up 6 months later without the need for lung transplantation during the study period.


A novel antibiotic strategy with a CIBL antibiotic and HDEI tobramycin improved survival in a small cohort of critically ill CF patients with end-stage lung disease and malnutrition requiring IMV.


Cystic fibrosis Invasive mechanical ventilation Continuous infusion β-Lactam antibiotic Respiratory failure Tobramycin Pseudomonas aeruginosa 



The authors greatly appreciated the outstanding assistance of Linda Combs in the preparation and development of the manuscript.


There are no conflicts of interest to declare.


  1. 1.
    Boat TF, Cheng PW (1989) Epithelial cell dysfunction in cystic fibrosis: implications for airways disease. Acta Paediatr Scand Suppl 363:25–29; discussion 29–30PubMedGoogle Scholar
  2. 2.
    Matsui H, Randell SH, Peretti SW, Davis CW, Boucher RC (1998) Coordinated clearance of periciliary liquid and mucus from airway surfaces. J Clin Invest 102(6):1125–1131PubMedCrossRefGoogle Scholar
  3. 3.
    Puchelle E, Bajolet O, Abély M (2002) Airway mucus in cystic fibrosis. Paediatr Respir Rev 3:115–119PubMedCrossRefGoogle Scholar
  4. 4.
    Ulrich M, Worlitzsch D, Viglio S et al (2010) Alveolar inflammation in cystic fibrosis. J Cyst Fibros 9:217–227PubMedCrossRefGoogle Scholar
  5. 5.
    Davis PB (1999) Clinical pathophysiology and manifestations of lung disease. In: Yankaskas JR, Knowles MR (eds) Cystic fibrosis in adults, 1st edn. Lippincott-Raven, Philadelphia, pp 45–67Google Scholar
  6. 6.
    Davis PB, di Sant’Agnese PA (1974) Assisted ventilation for patients with cystic fibrosis. JAMA 239:1851–1854CrossRefGoogle Scholar
  7. 7.
    Lloyd-Still JD, Khaw KT, Shwachman H (1974) Severe respiratory disease in infants with cystic fibrosis. Pediatrics 53:678–682PubMedGoogle Scholar
  8. 8.
    Garland JS, Chan YM, Kelly KJ, Rice TB (1989) Outcome of infants with cystic fibrosis requiring mechanical ventilation for respiratory failure. Chest 96:136–138PubMedCrossRefGoogle Scholar
  9. 9.
    Sood N, Paradowski LJ, Yankaskas JR (2001) Outcomes of intensive care unit care in adults with cystic fibrosis. Am J Respir Crit Care Med 163:335–338PubMedGoogle Scholar
  10. 10.
    Berlinski A, Fan LL, Kozinetz CA, Oermann CM (2002) Invasive mechanical ventilation for acute respiratory failure in children with cystic fibrosis: outcome analysis and case-control study. Pediatr Pulmonol 34:297–303PubMedCrossRefGoogle Scholar
  11. 11.
    Vedam H, Moriarty C, Torzillo PJ, McWilliam D, Bye PT (2004) Improved outcomes of patients with cystic fibrosis admitted to the intensive care unit. J Cyst Fibros 3:8–14PubMedCrossRefGoogle Scholar
  12. 12.
    Slieker MG, van Gestel JP, Heijerman HG et al (2006) Outcome of assisted ventilation for acute respiratory failure in cystic fibrosis. Intensive Care Med 32:754–758PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenstein BJ, Cutting GR (1998) The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 132:589–595PubMedCrossRefGoogle Scholar
  14. 14.
    Padoan R, Cambisano W, Costantini D et al (1987) Ceftazidime monotherapy vs. combined therapy in Pseudomonas pulmonary infections in cystic fibrosis. Pediatr Infect Dis J 6:648–653PubMedCrossRefGoogle Scholar
  15. 15.
    Leeder JS, Spino M, Isles AF, Tesoro AM, Gold R, MacLeod SM (1984) Ceftazidime disposition in acute and stable cystic fibrosis. Clin Pharmacol Ther 36:355–362PubMedCrossRefGoogle Scholar
  16. 16.
    Rappaz I, Decosterd LA, Bille J, Pilet M, Bélaz N, Roulet M (2000) Continuous infusion of ceftazidime with a portable pump is as effective as thrice-a-day bolus in cystic fibrosis children. Eur J Pediatr 159:919–925PubMedCrossRefGoogle Scholar
  17. 17.
    Roosendaal R, Bakker-Woudenberg IA, Van den Berghe Van-Raffe M, Vink-van den Berg JC, Michel BM (1989) Impact of the dosage schedule on the efficacy of ceftazidime, gentamicin and ciprofloxacin in Klebsiella pneumoniae pneumonia and septicemia in leukopenic rats. Eur J Clin Microbiol Infect Dis 8:878–887PubMedCrossRefGoogle Scholar
  18. 18.
    Craig WA, Ebert SC (1992) Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother 36:2577–2583PubMedGoogle Scholar
  19. 19.
    Daenen S, Erjavec Z, Uges DR, De Vries-Hospers HG, De Jonge P, Halie MR (1995) Continuous infusion of ceftazidime in febrile neutropenic patients with acute myeloid leukemia. Eur J Clin Microbiol Infect Dis 14:188–192PubMedCrossRefGoogle Scholar
  20. 20.
    Nicolau DP, Nightingale CH, Banevicius MA, Fu Q, Quintiliani R (1996) Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections. Antimicrob Agents Chemother 40:61–64PubMedGoogle Scholar
  21. 21.
    Vogelman B, Craig WA (1986) Kinetics of antimicrobial activity. J Pediatr 108(5 Pt 2):835–840PubMedGoogle Scholar
  22. 22.
    Vondracek TG (1995) Beta-lactam antibiotics: is continuous infusion the preferred method of administration? Ann Pharmacother 29:415–424PubMedGoogle Scholar
  23. 23.
    Rafati MR, Rouini MR, Mojtahedzadeh M et al (2006) Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients. Int J Antimicrob Agents 28:122–127PubMedCrossRefGoogle Scholar
  24. 24.
    Lau WK, Mercer D, Itani KM et al (2006) Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection. Antimicrob Agents Chemother 50:3556–3561PubMedCrossRefGoogle Scholar
  25. 25.
    Roberts JA, Paratz J, Paratz E, Krueger WA, Lipman J (2007) Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role. Int J Antimicrob Agents 30:11–18PubMedCrossRefGoogle Scholar
  26. 26.
    Roberts JA, Webb S, Paterson D, Ho KM, Lipman J (2009) A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics. Crit Care Med 37:2071–2078PubMedCrossRefGoogle Scholar
  27. 27.
    Riethmueller J, Junge S, Schroeter TW et al (2009) Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal therapy in cystic fibrosis. Infection 37:418–423PubMedCrossRefGoogle Scholar
  28. 28.
    Hubert D, Le Roux E, Lavrut T et al (2009) Continuous versus intermittent infusions of ceftazidime for treating exacerbation of cystic fibrosis. Antimicrob Agents Chemother 53:3650–3656PubMedCrossRefGoogle Scholar
  29. 29.
    Paradisi F, Corti G (1995) Once-daily dosing regimen for aminoglycoside plus betalactam combination therapy of serious lower respiratory tract infections. J Chemother 7:338–343PubMedGoogle Scholar
  30. 30.
    Powell SH, Thompson WL, Luthe MA et al (1983) Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin. J Infect Dis 147:918–932PubMedCrossRefGoogle Scholar
  31. 31.
    Bates RD, Nahata MC, Jones JW et al (1997) Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis. Chest 112:1208–1213PubMedCrossRefGoogle Scholar
  32. 32.
    Bragonier R, Brown NM (1998) The pharmacokinetics and toxicity of once-daily tobramycin therapy in children with cystic fibrosis. J Antimicrob Chemother 42:103–106PubMedCrossRefGoogle Scholar
  33. 33.
    Vic P, Ategbo S, Turck D et al (1998) Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis. Arch Dis Child 78:536–539PubMedCrossRefGoogle Scholar
  34. 34.
    Aminimanizani A, Beringer PM, Kang J, Tsang L, Jelliffe RW, Shapiro BJ (2002) Distribution and elimination of tobramycin administered in single or multiple daily doses in adult patients with cystic fibrosis. J Antimicrob Chemother 50:553–559PubMedCrossRefGoogle Scholar
  35. 35.
    Smyth A, Tan KH, Hyman-Taylor P et al (2005) Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis–the TOPIC study: a randomised controlled trial. Lancet 365:573–578PubMedGoogle Scholar
  36. 36.
    Riethmueller J, Ballmann M, Schroeter TW et al (2009) Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients. Infection 37:424–431PubMedCrossRefGoogle Scholar
  37. 37.
    Burkhardt O, Lehmann C, Madabushi R, Kumar V, Derendorf H, Welte T (2006) Once-daily tobramycin in cystic fibrosis: better for clinical outcome than thrice-daily tobramycin but more resistance development? J Antimicrob Chemother 58:822–829PubMedCrossRefGoogle Scholar
  38. 38.
    Soulsby N, Bell S, Greville H, Doecke C (2009) Intravenous aminoglycoside usage and monitoring of patients with cystic fibrosis in Australia. What’s new? Intern Med J 39:527–531PubMedCrossRefGoogle Scholar
  39. 39.
    Prescott WA Jr, Nagel JL (2010) Extended-interval once-daily dosing of aminoglycosides in adult and pediatric patients with cystic fibrosis. Pharmacotherapy 30:95–108PubMedCrossRefGoogle Scholar
  40. 40.
    Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, Ioannidis JP (2004) Extended-interval aminoglycoside administration for children: a meta-analysis. Pediatrics 114:e111–e118PubMedCrossRefGoogle Scholar
  41. 41.
    Smyth AR, Bhatt J (2010) Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev (1):CD002009Google Scholar
  42. 42.
    Flume PA, Mogayzel PJ Jr, Robinson KA et al (2009) Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med 180:802–808PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Advanced Lung Disease and Lung Transplant ProgramsC424 University of Kentucky Medical CenterLexingtonUSA
  2. 2.Department of Pharmaceutical Sciences-Drug Development DivisionUniversity of Kentucky College of PharmacyLexingtonUSA

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