, Volume 67, Issue 3, pp 351–368 | Cite as

The Epidemiology, Pathogenesis and Treatment of Pseudomonas aeruginosa Infections

  • James A. Driscoll
  • Steven L. Brody
  • Marin H. KollefEmail author
Review Article


Pseudomonas aeruginosa is an important bacterial pathogen, particularly as a cause of infections in hospitalised patients, immunocompromised hosts and patients with cystic fibrosis. Surveillance of nosocomial P. aeruginosa infections has revealed trends of increasing antimicrobial resistance, including carbapenem resistance and multidrug resistance. Mechanisms of antimicrobial resistance include multidrug efflux pumps, β-lactamases and downregulation of outer membrane porins. Mechanisms of virulence include secreted toxins and the ability to form biofilms. The effective treatment of infections caused by P. aeruginosa includes prevention when possible, source control measures as necessary and prompt administration of appropriate antibacterial agents. Antibacterial de-escalation should be pursued in patients with an appropriate clinical response, especially when antibacterial susceptibilities are known. Multidrug-resistant P. aeruginosa may require treatment with less commonly used antibacterials (e.g. colistin), but newer anti-pseudomonal antibacterials are expected to be available in the near future.


Cystic Fibrosis Cystic Fibrosis Patient Colistin Doripenem Carbapenem Resistance 
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.



No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Bonten MJ, Bergmans DC, Speijer H, et al. Characteristics of polyclonal endemicity of P. aeruginosa aeruginosa colonization in intensive care units: implications for infection control. Am J Respir Crit Care Med 1999; 160: 1212–9PubMedGoogle Scholar
  2. 2.
    Pirnay JP, De Vos D, Cochez C, et al. Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol 2003; 41: 1192–202PubMedCrossRefGoogle Scholar
  3. 3.
    Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002; 122: 2115–21PubMedCrossRefGoogle Scholar
  4. 4.
    Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005; 128: 3854–62PubMedCrossRefGoogle Scholar
  5. 5.
    Osmon S, Ward S, Fraser VJ, et al. Hospital mortality for patients with bacteremia due to Staphyiococcus aureus or Pseudomonas aeruginosa. Chest 2004; 125: 607–16PubMedCrossRefGoogle Scholar
  6. 6.
    Harbarth S, Ferrière K, Hugonnet S, et al. Epidemiology and prognostic determinants of bloodstream infections in surgical intensive care. Arch Surg 2002; 137: 1353–9PubMedCrossRefGoogle Scholar
  7. 7.
    National Nosocomial Infections Surveillance System Report. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32: 470–85CrossRefGoogle Scholar
  8. 8.
    Biedenbach DJ, Moet GJ, Jones RN. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997–2002). Diagn Microbiol Infect Dis 2004; 50: 59–69PubMedCrossRefGoogle Scholar
  9. 9.
    Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005; 41: 848–54PubMedCrossRefGoogle Scholar
  10. 10.
    Pittet D, Harbarth S, Ruef C, et al. Prevalence and risk factors for nosocomial infections in four university hospitals in Switzerland. Infect Control Hosp Epidemiol 1999; 20: 37–42PubMedCrossRefGoogle Scholar
  11. 11.
    Lizioli A, Privitera G, Alliata E, et al. Prevalence of nosocomial infections in Italy: result from the Lombardy survey in 2000. J Hosp Infect 2003; 54: 141–8PubMedCrossRefGoogle Scholar
  12. 12.
    Kim JM, Park ES, Jeong JS, et al. Multicenter surveillance study for nosocomial infections in major hospitals in Korea. Nosocomial Infection Surveillance Committee of the Korean Society for Nosocomial Infection Control. Am J Infect Control 2000; 28: 454–8PubMedCrossRefGoogle Scholar
  13. 13.
    Erbay H, Yalcin AN, Serin S, et al. Nosocomial infections in intensive care unit in a Turkish university hospital: a 2-year survey. Intensive Care Med 2003; 29: 1482–8PubMedCrossRefGoogle Scholar
  14. 14.
    Rello J, Lorente C, Diaz E, et al. Incidence, etiology, and outcome of nosocomial pneumonia in ICU patients requiring percutaneous tracheotomy for mechanical ventilation. Chest 2003; 124: 2239–43PubMedCrossRefGoogle Scholar
  15. 15.
    Ibrahim EH, Ward S, Sherman G, et al. A comparative analysis of patients with early-onset vs late-onset nosocomial pneumonia in the ICU setting. Chest 2000; 117: 1434–42PubMedCrossRefGoogle Scholar
  16. 16.
    Richards MJ, Edwards JR, Culver DH, et al. Nosocomial infections in pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System. Pediatrics 1999; 103: e39PubMedCrossRefGoogle Scholar
  17. 17.
    Lari AR, Alaghehbandan R. Nosocomial infections in an Iranian burn care center. Burns 2000; 26: 737–40PubMedCrossRefGoogle Scholar
  18. 18.
    Erol S, Altoparlak U, Akcay MN, et al. Changes of microbial flora and wound colonization in burned patients. Burns 2004; 30: 357–61PubMedCrossRefGoogle Scholar
  19. 19.
    Song W, Lee KM, Kang HJ, et al. Microbiologie aspects of predominant bacteria isolated from the burn patients in Korea. Burns 2001; 27: 136–9PubMedCrossRefGoogle Scholar
  20. 20.
    Yildirim S, Nursal TZ, Tarim A, et al. Bacteriological profile and antibiotic resistance: comparison of findings in a burn intensive care unit, other intensive care units, and the hospital services unit of a single center. J Burn Care Rehabil 2005; 26: 488–92PubMedCrossRefGoogle Scholar
  21. 21.
    Weiss CA, Statz CL, Dahms RA, et al. Six years of surgical wound infection surveillance at a tertiary care center: review of the microbiologie and epidemiological aspects of 20,007 wounds. Arch Surg 1999; 134: 1041–8PubMedCrossRefGoogle Scholar
  22. 22.
    Arias CA, Quintero G, Vanegas BE, et al. Surveillance of surgical site infections: decade of experience at a Colombian tertiary care center. World J Surg 2003; 27: 529–33PubMedCrossRefGoogle Scholar
  23. 23.
    Chan RK, Lye WC, Lee EJ, et al. Nosocomial urinary tract infection: a microbiological study. Ann Acad Med Singapore 1993; 22: 873–7PubMedGoogle Scholar
  24. 24.
    Jodrá VM, Díaz-Agero Pérez C, Sainz de Los Terreros Soler L, et al. Results of the Spanish national nosocomial infection surveillance network (VICONOS) for surgery patients from January 1997 through December 2003. Am J Infect Control 2006; 34: 134–41PubMedCrossRefGoogle Scholar
  25. 25.
    Bouza E, San Juan R, Muñoz P, et al. A European perspective on nosocomial urinary tract infections. I: report on the microbiology workload, etiology and antimicrobial susceptibility (ESGNI-003 study). European Study Group on Nosocomial Infections. Clin Microbiol Infect 2001; 7: 523–31PubMedCrossRefGoogle Scholar
  26. 26.
    Taneja N, Emmanuel R, Chari PS, et al. A prospective study of hospital-acquired infections in burn patients at a tertiary care referral centre in North India. Burns 2004; 30: 665–9PubMedCrossRefGoogle Scholar
  27. 27.
    Lee WI, Jaing TH, Hsieh MY, et al. Distribution, infections, treatments and molecular analysis in a large cohort of patients with primary immunodeficiency diseases (PIDs) in Taiwan. J Clin Immunol 2006; 26: 274–83PubMedCrossRefGoogle Scholar
  28. 28.
    Chatzinikolaou I, Abi-Said D, Bodey GP, et al. Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer: retrospective analysis of 245 episodes. Arch Intern Med 2000; 160: 501–9PubMedCrossRefGoogle Scholar
  29. 29.
    Funada H, Matsuda T. Changes in the incidence and etiological patterns of bacteremia associated with acute leukemia over a 25-year period. Intern Med 1998; 37: 1014–8PubMedCrossRefGoogle Scholar
  30. 30.
    Vidal F, Mensa J, Martinez JA, et al. Pseudomonas aeruginosa bacteremia in patients infected with human immunodeficiency virus type 1. Eur J Clin Microbiol Infect Dis 1999; 18: 473–7PubMedCrossRefGoogle Scholar
  31. 31.
    Afessa B, Green B. Bacterial pneumonia in hospitalized patients with HIV infection: the Pulmonary Complications, ICU Support, and Prognostic Factors of Hospitalized Patients with HIV (PIP) Study. Chest 2000; 117: 1017–22PubMedCrossRefGoogle Scholar
  32. 32.
    Afessa B, Green W, Chiao J, et al. Pulmonary complications of HIV infection: autopsy findings. Chest 1998; 113: 1225–9PubMedCrossRefGoogle Scholar
  33. 33.
    Lossos IS, Breuer R, Or R, et al. Bacterial pneumonia in recipients of bone marrow transplantation: a five-year prospective study. Transplantation 1995; 60: 672–8PubMedCrossRefGoogle Scholar
  34. 34.
    Kramer MR, Marshall SE, Starnes VA, et al. Infectious complications in heart-lung transplantation: analysis of 200 episodes. Arch Intern Med 1993; 153: 2010–6PubMedCrossRefGoogle Scholar
  35. 35.
    Revuz J, Penso D, Roujeau JC, et al. Toxic epidermal necrolysis: clinical findings and prognosis factors in 87 patients. Arch Dermatol 1987; 123: 1160–5PubMedCrossRefGoogle Scholar
  36. 36.
    Shankar EM, Mohan V, Premalatha G, et al. Bacterial etiology of diabetic foot infections in South India. Eur J Intern Med 2005; 16: 567–70PubMedCrossRefGoogle Scholar
  37. 37.
    Abdulrazak A, Bitar ZI, Al-Shamali AA, et al. Bacteriological study of diabetic foot infections. J Diabetes Complications 2005; 19: 138–41PubMedCrossRefGoogle Scholar
  38. 38.
    Burns JL, Gibson RL, McNamara S, et al. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis 2001; 183: 444–52PubMedCrossRefGoogle Scholar
  39. 39.
    Van Daele S, Vaneechoutte M, De Boeck K, et al. Survey of Pseudomonas aeruginosa genotypes in colonised cystic fibrosis patients. Eur Respir J 2006; 28: 740–7PubMedCrossRefGoogle Scholar
  40. 40.
    Lee B, Haagensen JA, Ciofu O, et al. Heterogeneity of biofilms formed by nonmucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. J Clin Microbiol 2005; 43: 5247–55PubMedCrossRefGoogle Scholar
  41. 41.
    Emerson J, Rosenfeld M, McNamara S, et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol 2002; 34: 91–100PubMedCrossRefGoogle Scholar
  42. 42.
    Holzmann D, Speich R, Kaufmann T, et al. Effects of sinus surgery in patients with cystic fibrosis after lung transplantation: a 10-year experience. Transplantation 2004; 77: 134–6PubMedCrossRefGoogle Scholar
  43. 43.
    D’Agata EM. Rapidly rising prevalence of nosocomial multidrug-resistant, gram-negative bacilli: a 9-year surveillance study. Infect Control Hosp Epidemiol 2004; 25: 842–6PubMedCrossRefGoogle Scholar
  44. 44.
    O’Toole GA, Kolter R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 1998; 30: 295–304PubMedCrossRefGoogle Scholar
  45. 45.
    Kipnis E, Sawa T, Wiener-Kronish J. Targeting mechanisms of Pseudomonas aeruginosa pathogenesis. Med Mal Infect 2006; 36: 78–91PubMedCrossRefGoogle Scholar
  46. 46.
    Lau GW, Hassett DJ, Britigan BE. Modulation of lung epithelial functions by Pseudomonas aeruginosa. Trends Microbiol 2005; 13: 389–97PubMedCrossRefGoogle Scholar
  47. 47.
    de Bentzmann S, Roger P, Puchelle E. Pseudomonas aeruginosa adherence to remodelling respiratory epithelium. Eur RespirJ 1996; 9: 2145–50CrossRefGoogle Scholar
  48. 48.
    Ramsey DM, Wozniak DJ. Understanding the control of Pseudomonas aeruginosa alginate synthesis and the prospects for management of chronic infections in cystic fibrosis. Mol Microbiol 2005; 56: 309–22PubMedCrossRefGoogle Scholar
  49. 49.
    Singh PK, Schaefer AL, Parsek MR, et al. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 2000; 407: 762–4PubMedCrossRefGoogle Scholar
  50. 50.
    Smith RS, Iglewski BH. P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol 2003; 6: 56–60PubMedCrossRefGoogle Scholar
  51. 51.
    Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol 2003; 57: 677–701PubMedCrossRefGoogle Scholar
  52. 52.
    Trautner BW, Darouiche RO. Catheter-associated infections: pathogenesis affects prevention. Arch Intern Med 2004; 164: 842–50PubMedCrossRefGoogle Scholar
  53. 53.
    Smith RS, Harris SG, Phipps R, et al. The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 2002; 184: 1132–9PubMedCrossRefGoogle Scholar
  54. 54.
    Rumbaugh KP, Griswold JA, Iglewski BH, et al. Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections. Infect Immun 1999; 67: 5854–62PubMedGoogle Scholar
  55. 55.
    Pearson JP, Feldman M, Iglewski BH, et al. Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection. Infect Immun 2000; 68: 4331–4PubMedCrossRefGoogle Scholar
  56. 56.
    Sadikot RT, Blackwell TS, Christman JW, et al. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med 2005; 171: 1209–23PubMedCrossRefGoogle Scholar
  57. 57.
    Hauser AR, Cobb E, Bodi M, et al. Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med 2002; 30: 521–8PubMedCrossRefGoogle Scholar
  58. 58.
    Schulert GS, Feltman H, Rabin SD, et al. Secretion of the toxin ExoU is a marker for highly virulent Pseudomonas aeruginosa isolates obtained from patients with hospital-acquired pneumonia. J Infect Dis 2003; 188: 1695–706PubMedCrossRefGoogle Scholar
  59. 59.
    Roy-Burman A, Savel RH, Racine S, et al. Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J Infect Dis 2001; 183: 1767–74PubMedCrossRefGoogle Scholar
  60. 60.
    Shime N, Sawa T, Fujimoto J, et al. Therapeutic administration of anti-PcrV F(ab’)(2) in sepsis associated with Pseudomonas aeruginosa. J Immunol 2001; 167: 5880–6PubMedGoogle Scholar
  61. 61.
    Faure K, Fujimoto J, Shimabukuro DW, et al. Effects of monoclonal anti-PcrV antibody on Pseudomonas aeruginosa-induced acute lung injury in a rat model. J Immune Based Ther Vaccines 2003; 1: 2PubMedCrossRefGoogle Scholar
  62. 62.
    Mariencheck WI, Alcorn JF, Palmer SM, et al. Pseudomonas aeruginosa elastase degrades surfactant proteins A and D. Am J Respir Cell Mol Biol 2003; 28: 528–37PubMedCrossRefGoogle Scholar
  63. 63.
    Schmidtchen A, Holst E, Tapper H, et al. Elastase-producing Pseudomonas aeruginosa degrade plasma proteins and extracellular products of human skin and fibroblasts, and inhibit fibroblast growth. Microb Pathog 2003; 34: 47–55PubMedCrossRefGoogle Scholar
  64. 64.
    Schmidtchen A, Frick IM, Andersson E, et al. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 2002; 46: 157–68PubMedCrossRefGoogle Scholar
  65. 65.
    Engel LS, Hill JM, Caballero AR, et al. Protease IV, a unique extracellular protease and virulence factor from Pseudomonas aeruginosa. J Biol Chem 1998; 273: 16792–7PubMedCrossRefGoogle Scholar
  66. 66.
    Carmeli Y, Troillet N, Eliopoulos GM, et al. Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 1999; 43: 1379–82PubMedGoogle Scholar
  67. 67.
    Schweizer HP. Efflux as a mechanism of resistance to antimicrobials in Pseudomonas aeruginosa and related bacteria: unanswered questions. Genet Mol Res 2003; 2: 48–62PubMedGoogle Scholar
  68. 68.
    Tamber S, Hancock RE. On the mechanism of solute uptake in Pseudomonas. Front Biosci 2003; 8: s472–83PubMedCrossRefGoogle Scholar
  69. 69.
    Hancock RE, Speert DP. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and impact on treatment. Drug Resist Updat 2000; 3: 247–55PubMedCrossRefGoogle Scholar
  70. 70.
    Pai H, Kim J, Lee JH, et al. Carbapenem resistance mechanisms in Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 2001; 45: 480–4PubMedCrossRefGoogle Scholar
  71. 71.
    Köhler T, Michea-Hamzehpour M, Epp SF, et al. Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Antimicrob Agents Chemother 1999; 43: 424–7PubMedGoogle Scholar
  72. 72.
    Sasaki M, Hiyama E, Takesue Y, et al. Clinical surveillance of surgical imipenem-resistant Pseudomonas aeruginosa infection in a Japanese hospital. J Hosp Infect 2004; 56: 111–8PubMedCrossRefGoogle Scholar
  73. 73.
    Aeschlimann JR. The role of multidrug efflux pumps in the antibiotic resistance of Pseudomonas aeruginosa and other gram-negative bacteria: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2003; 23: 916–24PubMedCrossRefGoogle Scholar
  74. 74.
    Jalal S, Ciofu O, Hoiby N, et al. Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 2000; 44: 710–2PubMedCrossRefGoogle Scholar
  75. 75.
    Hanson ND. AmpC beta-lactamases: what do we need to know for the future? J Antimicrob Chemother 2003; 52: 2–4PubMedCrossRefGoogle Scholar
  76. 76.
    Weldhagen GF, Poirel L, Nordmann P. Ambler class A extended-spectrum beta-lactamases in Pseudomonas aeruginosa: novel developments and clinical impact. Antimicrob Agents Chemother 2003; 47: 2385–92PubMedCrossRefGoogle Scholar
  77. 77.
    Weldhagen GF. Integrons and beta-lactamases: a novel perspective on resistance. Int J Antimicrob Agents 2004; 23: 556–62PubMedCrossRefGoogle Scholar
  78. 78.
    Lee K, Ha GY, Shin BM, et al. Metallo-beta-lactamase-producing gram-negative bacilli in Korean Nationwide Surveillance of Antimicrobial Resistance group hospitals in 2003: continued prevalence of VIM-producing Pseudomonas spp. and increase of IMP-producing Acinetobacter spp. Diagn Microbiol Infect Dis 2004; 50: 51–8PubMedCrossRefGoogle Scholar
  79. 79.
    Lagatolla C, Tonin EA, Monti-Bragadin C, et al. Endemic carbapenem-resistant Pseudomonas aeruginosa with acquired metallo-beta-lactamase determinants in European hospital. Emerg Infect Dis 2004; 10: 535–8PubMedCrossRefGoogle Scholar
  80. 80.
    Dubois V, Arpin C, Melon M, et al. Nosocomial outbreak due to a multiresistant strain of Pseudomonas aeruginosa P12: efficacy of cefepime-amikacin therapy and analysis of beta-lactam resistance. J Clin Microbiol 2001; 39: 2072–8PubMedCrossRefGoogle Scholar
  81. 81.
    Deplano A, Denis O, Poirel L, et al. Molecular characterization of an epidemic clone of panantibiotic-resistant Pseudomonas aeruginosa. J Clin Microbiol 2005; 43: 1198–204PubMedCrossRefGoogle Scholar
  82. 82.
    Chen HY, Yuan M, Livermore DM. Mechanisms of resistance to beta-lactam antibiotics amongst Pseudomonas aeruginosa isolates collected in the UK in 1993. J Med Microbiol 1995; 43: 300–9PubMedCrossRefGoogle Scholar
  83. 83.
    Mouneimné H, Robert J, Jarlier V, et al. Type II topoisomerase mutations in ciprofloxacin-resistant strains of Pseudomonas aeruginosa. Antimicrob Agents Chemother 1999; 43: 62–6PubMedGoogle Scholar
  84. 84.
    Zawacki A, O’Rourke E, Potter-Bynoe G, et al. An outbreak of Pseudomonas aeruginosa pneumonia and bloodstream infection associated with intermittent otitis externa in a healthcare worker. Infect Control Hosp Epidemiol 2004; 25: 1083–9PubMedCrossRefGoogle Scholar
  85. 85.
    McNeil SA, Nordstrom-Lerner L, Malani PN, et al. Outbreak of sternal surgical site infections due to Pseudomonas aeruginosa traced to a scrub nurse with onychomycosis. Clin Infect Dis 2001; 33: 317–23PubMedCrossRefGoogle Scholar
  86. 86.
    American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388–416CrossRefGoogle Scholar
  87. 87.
    O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control 2002; 30: 476–89PubMedCrossRefGoogle Scholar
  88. 88.
    Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999; 27: 97–132PubMedCrossRefGoogle Scholar
  89. 89.
    Bearman GM, Munro C, Sessler CN, et al. Infection control and the prevention of nosocomial infections in the intensive care unit. Semin Respir Crit Care Med 2006; 27: 310–24PubMedCrossRefGoogle Scholar
  90. 90.
    Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999; 115: 462–74PubMedCrossRefGoogle Scholar
  91. 91.
    Leibovici L, Shraga I, Drucker M, et al. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998; 244: 379–86PubMedCrossRefGoogle Scholar
  92. 92.
    Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32: 858–73PubMedCrossRefGoogle Scholar
  93. 93.
    Micek ST, Lloyd AE, Ritchie DJ, et al. Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother 2005; 49: 1306–11PubMedCrossRefGoogle Scholar
  94. 94.
    Paul M, Benuri-Silbiger I, Soares-Weiser K, et al. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668PubMedCrossRefGoogle Scholar
  95. 95.
    Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy reduce mortality in gram-negative bacteraemia? A meta-analysis. Lancet Infect Dis 2004; 4: 519–27PubMedCrossRefGoogle Scholar
  96. 96.
    Hilf M, Yu VL, Sharp J, et al. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 1989; 87: 540–6PubMedCrossRefGoogle Scholar
  97. 97.
    Kuikka A, Valtonen VV. Factors associated with improved outcome of Pseudomonas aeruginosa bacteremia in a Finnish university hospital. Eur J Clin Microbiol Infect Dis 1998; 17: 701–8PubMedCrossRefGoogle Scholar
  98. 98.
    Chamot E, Boffi El Amari E, Rohner P, et al. Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia. Antimicrob Agents Chemother 2003; 47: 2756–64PubMedCrossRefGoogle Scholar
  99. 99.
    Döring G, Conway SP, Heijerman HG, et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 2000; 16: 749–67PubMedCrossRefGoogle Scholar
  100. 100.
    Yankaskas JR, Marshall BC, Sufian B, et al. Cystic fibrosis adult care: consensus conference report. Chest 2004; 125: 1–39SCrossRefGoogle Scholar
  101. 101.
    Zaoutis TE, Goyal M, Chu JH, et al. Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children. Pediatrics 2005; 115: 942–9PubMedCrossRefGoogle Scholar
  102. 102.
    del Mar Tomas M, Cartelle M, Pertega S, et al. Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and risk-factors for colonisation and infection. Clin Microbiol Infect 2005; 11: 540–6PubMedCrossRefGoogle Scholar
  103. 103.
    Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588–98PubMedCrossRefGoogle Scholar
  104. 104.
    Cometta A, Baumgartner JD, Lew D, et al. Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients. Antimicrob Agents Chemother 1994; 38: 1309–13PubMedCrossRefGoogle Scholar
  105. 105.
    Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA 2000; 283: 1583–90PubMedCrossRefGoogle Scholar
  106. 106.
    Dunbar LM, Wunderink RG, Habib MP, et al. High-dose, shortcourse levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis 2003; 37: 752–60PubMedCrossRefGoogle Scholar
  107. 107.
    Kollef MH, Micek ST. Strategies to prevent antimicrobial resistance in the intensive care unit. Crit Care Med 2005; 33: 1845–53PubMedCrossRefGoogle Scholar
  108. 108.
    Kwa AL, Loh C, Low JG, et al. Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Infect Dis 2005; 41: 754–7PubMedCrossRefGoogle Scholar
  109. 109.
    Hamer DH. Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am J Respir Crit Care Med 2000; 162: 328–30PubMedGoogle Scholar
  110. 110.
    Levin AS, Barone AA, Penço J, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis 1999; 28: 1008–11PubMedCrossRefGoogle Scholar
  111. 111.
    Linden PK, Kusne S, Coley K, et al. Use of parenteral colistin for the treatment of serious infection due to antimicrobialresistant Pseudomonas aeruginosa. Clin Infect Dis 2003; 37: el54–60CrossRefGoogle Scholar
  112. 112.
    Garnacho-Montero J, Ortiz-Leyba C, Jiménez-Jiménez FJ, et al. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin Infect Dis 2003; 36: 1111–8PubMedCrossRefGoogle Scholar
  113. 113.
    Falagas ME, Fragoulis KN, Kasiakou SK, et al. Nephrotoxicity of intravenous colistin: a prospective evaluation. Int J Antimicrob Agents 2005; 26: 504–7PubMedCrossRefGoogle Scholar
  114. 114.
    Kasiakou SK, Michalopoulos A, Soteriades ES, et al. Combination therapy with intravenous colistin for management of infections due to multidrug-resistant gram-negative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemother 2005; 49: 3136–46PubMedCrossRefGoogle Scholar
  115. 115.
    Conway SP, Etherington C, Munday J, et al. Safety and tolerability of bolus intravenous colistin in acute respiratory exacerbations in adults with cystic fibrosis. Ann Pharmacother 2000; 34: 1238–42PubMedCrossRefGoogle Scholar
  116. 116.
    Falagas ME, Rizos M, Bliziotis IA, et al. Toxicity after prolonged (more than four weeks) administration of intravenous colistin. BMC Infect Dis 2005; 5: 1PubMedCrossRefGoogle Scholar
  117. 117.
    Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006; 10: R27PubMedCrossRefGoogle Scholar
  118. 118.
    Falagas ME, Kasiakou SK. Use of international units when dosing colistin will help decrease confusion related to various formulations of the drug around the world. Antimicrob Agents Chemother 2006; 50: 2274–5PubMedCrossRefGoogle Scholar
  119. 119.
    Jones RN, Huynh HK, Biedenbach DJ, et al. Doripenem (S-4661), a novel carbapenem: comparative activity against contemporarypathogens including bactericidal action and preliminary in vitro methods evaluations. J Antimicrob Chemother 2004; 54: 144–54PubMedCrossRefGoogle Scholar
  120. 120.
    Fritsche TR, Stilwell MG, Jones RN. Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003). Clin Microbiol Infect 2005; 11: 974–84PubMedCrossRefGoogle Scholar
  121. 121.
    Tsuji M, Ishii Y, Ohno A, et al. In vitro and in vivo antibacterial activities of S-4661, a new carbapenem. Antimicrob Agents Chemother 1998; 42: 94–9PubMedGoogle Scholar
  122. 122.
    Jones RN, Huynh HK, Biedenbach DJ. Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother 2004; 48: 3136–40PubMedCrossRefGoogle Scholar
  123. 123.
    Traczewski MM, Brown SD. In vitro activity of doripenem against Pseudomonas aeruginosa and Burkholderia cepacia isolates from both cystic fibrosis and non-cystic fibrosis patients. Antimicrob Agents Chemother 2006; 50: 819–21PubMedCrossRefGoogle Scholar
  124. 124.
    Mahadeva R, Webb K, Westerbeek RC, et al. Clinical outcome in relation to care in centres specialising in cystic fibrosis: cross sectional study. BMJ 1998; 316: 1771–5PubMedCrossRefGoogle Scholar
  125. 125.
    Kerem E, Conway S, Elborn S, et al. Standards of care for patients with cystic fibrosis: a European consensus. J Cyst Fibros 2005; 4: 7–26PubMedCrossRefGoogle Scholar
  126. 126.
    Wiesemann HG, Steinkamp G, Ratjen F, et al. Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. Pediatr Pulmonol 1998; 25: 88–92PubMedCrossRefGoogle Scholar
  127. 127.
    Frederiksen B, Koch C, Høiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997; 23: 330–5PubMedCrossRefGoogle Scholar
  128. 128.
    Moss RB. Long-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis. Chest 2002; 121: 55–63PubMedCrossRefGoogle Scholar
  129. 129.
    Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999; 340: 23–30PubMedCrossRefGoogle Scholar
  130. 130.
    Moss RB. Administration of aerosolized antibiotics in cystic fibrosis patients. Chest 2001; 120: 107–3SCrossRefGoogle Scholar
  131. 131.
    Levy J, Smith AL, Koup JR, et al. Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study. J Pediatr 1984; 105: 117–24PubMedCrossRefGoogle Scholar
  132. 132.
    de Groot R, Hack BD, Weber A, et al. Pharmacokinetics of ticarcillin in patients with cystic fibrosis: a controlled prospective study. Clin Pharmacol Ther 1990; 47: 73–8PubMedCrossRefGoogle Scholar
  133. 133.
    Stephens D, Garey N, Isles A, et al. Efficacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis. Pediatr Infect Dis 1983; 2: 209–11PubMedCrossRefGoogle Scholar
  134. 134.
    Schaad UB, Wedgwood-Krucko J, Suter S, et al. Efficacy of inhaled amikacin as adjunct to intravenous combination therapy (ceftazidime and amikacin) in cystic fibrosis. J Pediatr 1987; 111: 599–605PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • James A. Driscoll
    • 1
  • Steven L. Brody
    • 1
  • Marin H. Kollef
    • 1
    Email author
  1. 1.Division of Pulmonary and Critical Care MedicineWashington University School of MedicineSaint LouisUSA

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