Advertisement

Inhaled aminoglycosides in cancer patients with ventilator-associated Gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance

  • D. E. Ghannam
  • G. H. Rodriguez
  • I. I. Raad
  • A. Safdar
Article

Abstract

We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13% vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled antibiotics developed nephrotoxicity (P ≤ 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious toxicity and may lead to improved outcome.

Keywords

Cystic Fibrosis Aminoglycosides Tobramycin Colistin Critical Care Unit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This research was supported in part by the Cancer Center Support Grant CA16672 from the National Institutes of Health.

References

  1. 1.
    Safdar A, Armstrong D (2001) Infectious morbidity in critically ill patients with cancer. Crit Care Clin 17:531–570PubMedCrossRefGoogle Scholar
  2. 2.
    American Thoracic Society and Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416CrossRefGoogle Scholar
  3. 3.
    National Nosocomial Infections Surveillance (NNIS) (1999) System report, data summary from January 1990–May 1999, issued June 1999. Am J Infect Control 27:520–532CrossRefGoogle Scholar
  4. 4.
    Porzecanski I, Bowton DL (2006) Diagnosis and treatment of ventilator-associated pneumonia. Chest 130:597–604PubMedCrossRefGoogle Scholar
  5. 5.
    Davis KA (2006) Ventilator-associated pneumonia: a review. J Intensive Care Med 21:211–216PubMedCrossRefGoogle Scholar
  6. 6.
    Kiem S, Schentag JJ (2006) Relationship of minimal inhibitory concentration and bactericidal activity to efficacy of antibiotics for treatment of ventilator-associated pneumonia. Semin Respir Crit Care Med 27:51–67PubMedCrossRefGoogle Scholar
  7. 7.
    Brun-Buisson C, Lemaire F (2001) Administration of antibiotics for pneumonia during respiratory failure: reaching the target. Am J Respir Crit Care Med 164:1554–1555PubMedGoogle Scholar
  8. 8.
    Schmidt-loanas M, de Roux A, Lode H (2005) New antibiotics for the treatment of severe staphylococcal infection in the critically ill patients. Curr Opin Crit Care 11:481–486CrossRefGoogle Scholar
  9. 9.
    Canton R, Cobos N, de Gracia J, Baquero F, Honorato J, Gartner S et al (2005) Antimicrobial therapy for pulmonary pathogenic colonization and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Clin Microbiol Infect 11:690–703PubMedCrossRefGoogle Scholar
  10. 10.
    Brown RB, Kruse JA, Counts GW, Russell JA, Christou NV, Sands ML (2005) Double-blind study of endotracheal tobramycin in the treatment of gram-negative bacterial pneumonia. Antimicrob Agents Chemother 34:269–272Google Scholar
  11. 11.
    Kwa AL, Loh C, Low JG, Kurup A, Tam VH (2005) Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Infect Dis 41:754–757PubMedCrossRefGoogle Scholar
  12. 12.
    Hamer DH (2000) Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am J Respir Crit Care Med 162:328–330PubMedGoogle Scholar
  13. 13.
    Michalopoulos A, Kasiakou SK, Mastora Z, Rellos K, Kapaskelis AM, Falagas ME (2005) Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis. Crit Care 9:R53–R59PubMedCrossRefGoogle Scholar
  14. 14.
    Luna CM, Blanzaco D, Niederman MS, Matarucco W, Baredes NC, Desmery P et al (2003) Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 31:676–682PubMedCrossRefGoogle Scholar
  15. 15.
    Jarvis WR, Edwards JR, Culver DH, Hughes JM, Horan T, Emori TG et al (1991) Nosocomial infection rates in adult and pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System. Am J Med 91:185–191CrossRefGoogle Scholar
  16. 16.
    Conrad DJ (2003) The clinical use of aerosolized antibiotics. Clin Pulm Med 10:201–207CrossRefGoogle Scholar
  17. 17.
    Palmer LB, Smaldone GC, Simon SR, O’Riordan TG, Cuccia A (1998) Aerosolized antibiotics in mechanically ventilated patients: delivery and response. Crit Care Med 26:31–39PubMedCrossRefGoogle Scholar
  18. 18.
    Goldstein I, Chastre J, Rouby JJ (2006) Novel and innovative strategies to treat ventilator-associated pneumonia: optimizing the duration of therapy and nebulizing antimicrobial agents. Semin Respir Crit Care Med 27:82–91PubMedCrossRefGoogle Scholar
  19. 19.
    Geller DE, Pitlick WH, Nardella PA, Tracewell WG, Ramsey BW (2002) Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest 122:219–226PubMedCrossRefGoogle Scholar
  20. 20.
    Fuller HD, Dolovich MB, Posmituck G, Pack WW, Newhouse MT (1989) Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Am Rev Respir Dis 141:440–444Google Scholar
  21. 21.
    MacIntyre NR, Silver RM, Miller CW, Schuler F, Colman RE (1985) Aerosol delivery to intubated, mechanically ventilated patients. Crit Care Med 13:81–84PubMedCrossRefGoogle Scholar
  22. 22.
    Palmer LB, Smaldone GC, Simon S, O’Riordan T, Morra L (1995) Tracheal aspirate in long-term mechanically ventilated patients. A human model of gram-negative infection and airway inflammation. Chest 108:1326–1332PubMedCrossRefGoogle Scholar
  23. 23.
    Ilowite JS, Gorvoy JD, Smaldone GC (1987) Quantitative deposition of aerosolized gentamicin in cystic fibrosis. Am Rev Respir Dis 136:1445–1449PubMedGoogle Scholar
  24. 24.
    Smaldone GC, Fuhrer JT, Steigbigel RT, McPeck M (1991) Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection. Am Rev Respir Dis 143:727–737PubMedGoogle Scholar
  25. 25.
    Drobnic ME, Sune P, Montoro JB, Ferrer A, Orriols R (2005) Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother 39:39–44PubMedGoogle Scholar
  26. 26.
    Linden P, Paterson DL (2006) Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis 43:S89–S94PubMedCrossRefGoogle Scholar
  27. 27.
    Le Conte P, Potel G, Peltier P, Horeau D, Caillon J, Juvin ME et al (1993) Lung distribution and pharmacokinetics of aerosolized tobramycin. Am Rev Respir Dis 147:1279–1282PubMedGoogle Scholar
  28. 28.
    Adair CG, Gorman SP, O’Neill FB, McClurg B, Goldsmith EC, Webb CH (1993) Selective decontamination of the digestive tract (SDD) does not prevent the formation of microbial biofilms on endotracheal tubes. J Antimicrob Chemother 31:689–697PubMedCrossRefGoogle Scholar
  29. 29.
    Adair CG, Gorman SP, Byers LM, Jones DS, Feron B, Crowe M et al (2002) Eradication of endotracheal tube biofilm by nebulised gentamicin. Intensive Care Med 28:426–431PubMedCrossRefGoogle Scholar
  30. 30.
    Lesho E (2005) Role of inhaled antibacterials in hospital-acquired and ventilator-associated pneumonia. Expert Rev Anti Infect Ther 3:445–451PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • D. E. Ghannam
    • 1
  • G. H. Rodriguez
    • 1
  • I. I. Raad
    • 1
  • A. Safdar
    • 1
  1. 1.Department of Infectious Diseases, Infection Control, and Employee Health, Unit 402The University of Texas M.D. Anderson Cancer CenterHoustonUSA

Personalised recommendations