Pseudomonas aeruginosa, Candida albicans, and device-related nosocomial infections: implications, trends, and potential approaches for control

  • George E. PierceEmail author
Special Topic: Disinfectants and Microbial Control


For many years, device-associated infections and particularly device-associated nosocomial infections have been of considerable concern. Recently, this concern was heightened as a result of increased antibiotic resistance among the common causal agents of nosocomial infections, the appearance of new strains which are intrinsically resistant to the antibiotics of choice, and the emerging understanding of the role biofilms may play in device-associated infections and the development of increased antibiotic resistance. Pseudomonas aeruginosa and Candida albicans are consistently identified as some of the more important agents of nosocomial infections. In light of the recent information regarding device-associated nosocomial infections, understanding the nature of P. aeruginosa and C. albicans infections is increasingly important. These two microorganisms demonstrate: (1) an ability to form biofilms on the majority of devices employed currently, (2) increased resistance/tolerance to antibiotics when associated with biofilms, (3) documented infections noted for virtually all indwelling devices, (4) opportunistic pathogenicity, and (5) persistence in the hospital environment. To these five demonstrated characteristics, two additional areas of interest are emerging: (a) the as yet unclear relationship of these two microorganisms to those species of highly resistant Pseudomonas spp and Candida spp that are of increasing concern with device-related infections, and (b) the recent research showing the dynamic interaction of P. aeruginosa and C. albicans in patients with cystic fibrosis. An understanding of these two opportunistic pathogens in the context of their ecosystems/biofilms also has significant potential for the development of novel and effective approaches for the control and treatment of device-associated infections.


Nosocomial infection Pseudomonas Candida 


  1. 1.
    Babcock HM, Zack JE, Garrison T, Trovillion E, Kollef MH, Fraser VJ (2003) Ventilator-associated pneumonia in a multi-hospital system: difference in microbiology by location. Infect Control Hosp Epidemiol 24:853–858PubMedGoogle Scholar
  2. 2.
    Berthelot P, Grattard F, Mahul P, Pain P, Jospe R, Venet C, Carricajo A, Aubert G, Ros A, Dumont A, Lucht F, Zeni F, Auboyer C, Bertrand J-C, Pozzetto B (2001) Prospective study of nosocomial colonization and infection due to Pseudomonas aeruginosa in mechanically ventilated patients. Intensive Care Med 27:503–512CrossRefPubMedGoogle Scholar
  3. 3.
    Bindhu M, Smith JN, Swift S, Heffron F, Ahmer BMM (2001) SdiA of Salmonella enterica is a LuxR homology that detects mixed microbial communities. J Bacteriol 183:5733–5742CrossRefPubMedGoogle Scholar
  4. 4.
    Cai S, Zhang J, Qian G (2001) Correlation of endotracheal tube biofilm and recurrent ventilator-associated pneumonia with Pseudomonas aeruginosa. Zhonghua Jie He 24:339–341Google Scholar
  5. 5.
    Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA (2001) Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 183:5385–5394CrossRefPubMedGoogle Scholar
  6. 6.
    Chastre J, Fagon J-V (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903PubMedGoogle Scholar
  7. 7.
    Chui HH, Huang LM, Lee PI, Lee CY (1998) Bacteremia and fungemia in hematological and oncological children with neutropenic fever: two-year study in a medical center. J Microbiol Immunol Infect 31:101–106PubMedGoogle Scholar
  8. 8.
    Clegg H, Cram WS, DeGroot-Kosolcharoen J, Garibaldi R, Kass EH, Kunin CM, Lindan R, Stamm WE (1979) Guideline for prevention of catheter-associated urinary tract infections. (CDC guides.) CDC, Atlanta, pp 1–9Google Scholar
  9. 9.
    Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Annu Rev Microbiol 49:711–746CrossRefPubMedGoogle Scholar
  10. 10.
    Dariouche RO (2001) Device-associated infections: a macroproblem that starts with microadherence. Clin Infect Dis 33:1567–1572CrossRefPubMedGoogle Scholar
  11. 11.
    Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280:295–298CrossRefPubMedGoogle Scholar
  12. 12.
    De Kievit TR, Gillis R, Marx S, Brown C, Iglewski BH (2001) Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Appl Environ Microbiol 67:1865–1873CrossRefPubMedGoogle Scholar
  13. 13.
    De Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immun 68:4839–4849CrossRefPubMedGoogle Scholar
  14. 14.
    Denstedt J, Wollin T, Reid G (1998) Biomaterials used in urology: current issues of biocompatibility, infection, and encrustation. J Endourol 12:493–500PubMedGoogle Scholar
  15. 15.
    Diekema DJ, Pfaller MA (2004) Nosocomial candidemia: an ounce of prevention is better than a pound of cure. Infect Control Hosp Epidemiol 25:624–626PubMedGoogle Scholar
  16. 16.
    Dong YH, Wang LH, Xu JL, Zhang HB, Zhang XF, Zhang LH (2001) Quenching quorum-sensing dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411:813–817CrossRefPubMedGoogle Scholar
  17. 17.
    Donlan RM (2000) Role of biofilms in antimicrobial resistance. ASAIO J 46:S47–S52CrossRefPubMedGoogle Scholar
  18. 18.
    Donlan RM (2002) Biofilms: microbial life on surfaces. Emerg Infect Dis 8:1–19PubMedGoogle Scholar
  19. 19.
    Douglas LJ (2003) Candida biofilms and their role in infection. Trends Microbiol 11:30–36CrossRefPubMedGoogle Scholar
  20. 20.
    Edgeworth JD, Treacher DF, Eykyn SJ (1999) A 25-year study of nosocomial bacteremia in an adult intensive care unit. Crit Care Med 27:1421–1428CrossRefPubMedGoogle Scholar
  21. 21.
    El-Ebiary M, Torres A, Fabregas N, Bellacasa JP de la, Gonzalez J, Ramirez J, Bano D del, Hernandes C, Ana MTJ de (1997) Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. Am J Respir Crit Care Med 156:583–590PubMedGoogle Scholar
  22. 22.
    Elishoov H, Or R, Strauss N, Engelhard D (1998) Nosocomial colonization, septicemia, and Hickman/Broviac catheter-related infections in bone marrow transplant recipients: a 5-year prospective study. Medicine 77:83–101CrossRefPubMedGoogle Scholar
  23. 23.
    Folders J, Tommassen J, Loon LC van, Bitter W (2000) Identification of a chitin-binding protein secreted by Pseudomonas aeruginosa. J Bacteriol 182:1257–1263CrossRefPubMedGoogle Scholar
  24. 24.
    Folders J, Algra J, Roelofs MS, Loon LC van, Tommassen J, Bitter W (2001) Characterization of Pseudomonas aeruginosa chitinase, a gradually secreted protein. J Bacteriol 183:7044–7052CrossRefPubMedGoogle Scholar
  25. 25.
    Fridkin SK (2001) Increasing prevalence of antimicrobial resistance in intensive care units. Crit Care Med 29:N64–N68CrossRefPubMedGoogle Scholar
  26. 26.
    George M, Pierce GE, Gabriel M, Morris C, Ahearn DG (2005) Effects of quorum sensing molecules of Pseudomonas aeruginosa on organism growth, elastase B production, and primary adhesion to hydogel contact lenses. Eye Contact Lens 31:54–61CrossRefPubMedGoogle Scholar
  27. 27.
    Groot AJ, Geubbels EL, Beaumont MT, Wille JC, Boer AS de (2001) Hospital infections and risk factors in the intensive care units of 16 Dutch hospitals: results of surveillance of quality assurance indicators. Ned Tijdschr Geneeskd 145:1249–1254PubMedGoogle Scholar
  28. 28.
    Hajjeh RA, Sofair AN, Harrison LH, Lyon GM, Arthington-Skaggs BA, Mirza SA, Phelan M, Morgan J, Lee-Young W, Ciblak MA, Benjamin LE, Sanza LT, Huie S, Yeo SF, Brandt ME, Warnock DW (2004) Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol 42:1519–1527CrossRefPubMedGoogle Scholar
  29. 29.
    Hanlon G, Denyer S, Olliff C, Ibrahim LJ (2001) Reduction in exopolysaccharide viscosity as an aid to bacteriophage penetration through Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 67:2746–2753CrossRefPubMedGoogle Scholar
  30. 30.
    Hawser SP, Douglas LJ (1995) Resistance of Candida albicans biofilms to antifungal agents in vitro. Antimicrob Agents Chemother 39:2128–2131PubMedGoogle Scholar
  31. 31.
    Hogan DA, Kolter R (2002) PseudomonasCandida interactions: an ecological role for virulence factors. Science 296:2229–2232CrossRefPubMedGoogle Scholar
  32. 32.
    Hogan DA, Vik A, Kolter R (2004) A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology. Mol Microbiol 54:1212–1223CrossRefPubMedGoogle Scholar
  33. 33.
    Hornby JM, Jensen EC, Lisec AD, Tasto JJ, Jahnke B, Shoemaker R, Dussault P, Nickerson KW (2001) Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl Environ Microbiol 67:2982–2992CrossRefPubMedGoogle Scholar
  34. 34.
    Jabra-Rizk MA, Falkler WA, Meiller TF (2004) Fungal biofilms and drug resistance. Emerg Infect Dis 10:14–19PubMedGoogle Scholar
  35. 35.
    Jambasi RJ, Kennel SJ, Waters LC, Foote LJ, Ramsey JM (2004) Genetic analysis of Pseudomonas aeruginosa by enterobacterial repetitive intergenic consensus polymerase chain reactions (PCR) and arbitrarily primed PCR: gel analysis compared with microchip gel electrophoresis. Infect Control Hosp Epidemiol 25:65–71PubMedGoogle Scholar
  36. 36.
    Jones DS, McMeel S, Adair CG, Gorman SP (2003) Characterization and evaluation of novel surfactant bacterial anti-adherent coatings for endotracheal tubes designed for the prevention of ventilator-associated pneumonia. J Pharm Pharmacol 55:43–52PubMedGoogle Scholar
  37. 37.
    Kao AS, Brandt ME, Pruitt WR, Conn LA, Perkins BA, Stephens DS, Baughman WS, Reingold AL, Rothrock GA, Pfaller MA, Pinner RW, Hajjeh RA (1999) The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin Infect Dis 29:1164–1170CrossRefPubMedGoogle Scholar
  38. 38.
    Karchmer TB, Giannetta ET, Muto CA, Strain BA, Farr BM (2000) A randomized crossover study of silver-coated urinary catheters in hospitalized patients. Arch Intern Med 160:3294–3298CrossRefPubMedGoogle Scholar
  39. 39.
    Kojic E, Darouiche RO (2004) Candida infections of medical devices. Clin Microbiol Rev 17:255–267CrossRefPubMedGoogle Scholar
  40. 40.
    Kolter R, Losick R (1998) One for all and all for one. Science 280:226–227CrossRefPubMedGoogle Scholar
  41. 41.
    Lewis K (2001) Riddle of biofilm resistance. Antimicrob Agents Chemother 45:999–1007CrossRefPubMedGoogle Scholar
  42. 42.
    Lewis RE, Lo H-J, Raad II, Kontoyiannis DP (2002) Lack of catheter infection by the efg1/efg1, cph1/cph1 double-null mutant, a Candida albicans strain that is defective in filamentous growth. Antimicrob Agents Chemother 46:1153–1155CrossRefPubMedGoogle Scholar
  43. 43.
    Li X, Yan Z, Xu J (2003) Quantitative variation of biofilms among strains in natural populations of Candida albicans. Microbiology 149:353–362CrossRefPubMedGoogle Scholar
  44. 44.
    Lombardi G, Luzzaro F, Docquire J-D, Riccio ML, Perilli M, Coli A, Amicosante G, Rossolini GM, Toniolo A (2002) Nosocomial infections caused by multidrug-resistant isolates of Pseudomonas putida producing VIM-1 metallo-β-lactamase. J Clin Microb 40:4051–4055CrossRefGoogle Scholar
  45. 45.
    Lyte M, Freestone PPE, Neal CP, Olson BA, Haigh RD, Bayston R, Williams PH (2003) Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes. Lancet 361:130–135CrossRefPubMedGoogle Scholar
  46. 46.
    Maki DG, Knasinski V, Halvorson K, Tambyah PA (1998) A novel silver-hydrogel impregnated indwelling catheter reduces CAUTIs: a prospective double blind trial. In: Programs and abstracts of the society for healthcare epidemiology in America annual meeting. Society for Healthcare Epidemiology in America, OrlandoGoogle Scholar
  47. 47.
    Maki DG, Tambyah PA (2001) Engineering out the risk of infection with urinary catheters. Emerg Infect Dis 7:342–347PubMedGoogle Scholar
  48. 48.
    Mateus C, Ahearn DG, Crow SA (2004) Adherence of Candida albicans to silicones induces immediate enhanced tolerance to fluconazole. Antimicrob Agents Chemother 48:3358–3366CrossRefPubMedGoogle Scholar
  49. 49.
    Nahum E, Levy I, Katz J, Smara Z, Ashkenazi S, Ben-Ari J, Schonfeld T, Dagan O (2002) Efficacy of subcutaneous tunneling for prevention of bacterial colonization of femoral central venous catheters in critically ill children. Pediatr Infect Dis J 21:1000–1004CrossRefPubMedGoogle Scholar
  50. 50.
    Namiduru MG, Gungor, I Karaoglan, Dikensoy O (2004) Antibiotic resistance of bacterial ventilator-associated pneumonia in surgical intensive care units. J Int Med Res 32:87–83Google Scholar
  51. 51.
    NIAID (2000) Fifth NIAID workshop in medical mycology: epidemiology. Duke University, Durham, N.C., pp13–16Google Scholar
  52. 52.
    Niederman MS (2001) Impact of antibiotic resistance on clinical outcomes and the cost of care. Crit Care Med 29:N114–N120CrossRefPubMedGoogle Scholar
  53. 53.
    NNIS (1999) National nosocomial infections surveillance (NNIS) system repot, data summary from January 1990 through May 1999. Am J Infect Control 27:520–532PubMedGoogle Scholar
  54. 54.
    NNIS (2003) National nosocomial infections surveillance (NNIS) system repot, data summary from January 1992 through June 2003. Am J Infect Control 31:481–498CrossRefPubMedGoogle Scholar
  55. 55.
    O’Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG, Masur H, McCormick RD, Mermel LA, Pearson ML, Raad II, Randolph A, Weinstein RA, Healthcare Infection Control Practices Advisory Committee (2002) Guidelines for the prevention of intravascular catheter-related infections. Infect Control Hosp Epidemiol 23:759–769PubMedGoogle Scholar
  56. 56.
    Orenstein R, Wong ES (1999) Urinary tract infections in adults. Am Fam Physician 59:1225–1236PubMedGoogle Scholar
  57. 57.
    Parsek MR, Greenberg EP (2000) Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling mechanism involved in associations with higher organisms. Proc Natl Acad Sci USA 97:8789–93CrossRefPubMedGoogle Scholar
  58. 58.
    Pawar M, Mehta Y, Khurana P, Chaudhary A, Kulkarni V, Trehan N (2003) Ventilator-associated pneumonia: incidence, risk factors, outcome, and microbiology. J Cardiothoracic Vasc Anesth 17:22–28CrossRefGoogle Scholar
  59. 59.
    Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Dickema DJ (2004) Cross-resistance between fluconazole and ravuconazole and the use of fluconazole as a surrogate market to predict susceptibility and resistance to ravuconazole among 12,796 clinical isolates of Candida spp. J Clin Microbiol 42:3137–3141CrossRefPubMedGoogle Scholar
  60. 60.
    Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ, Dickema DJ (2004) Geographic variation in the susceptibilities of invasive isolates of Candida glabrata to seven systemically active antifungal agents: a global assessment from the ARTEMIS antifungal surveillance program conducted in 2001 and 2002. J Clin Microbiol 42:3142–3146CrossRefPubMedGoogle Scholar
  61. 61.
    Pratt LA, Kolter R (1998) Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol Microbiol 30:285–293CrossRefPubMedGoogle Scholar
  62. 62.
    Raad I, Hanna H, Boktour M, Girgawy E, Danawi H, Mardani M, Kontoyiannis D, Darouiche R, Hachem R, Bodey GP (2004) Management of central venous catheters in patients with cancer and candidemia. Clin Infect Dis 38:1119–1127CrossRefPubMedGoogle Scholar
  63. 63.
    Ramage GK, Bachmann S, Patterson TF, Wickes BL, Lopez-Ribot JL (2002) Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother 49:973–980CrossRefPubMedGoogle Scholar
  64. 64.
    Ramage G, Walle K van de, Wickes BL, Lopez-Ribot JL (2001) Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob Agents Chemother 45:2475–2479CrossRefPubMedGoogle Scholar
  65. 65.
    Ramage G, Wickes BL, Lopez-Ribot JL (2001) Biofilms of Candida albicans and their associated resistance to antifungal agents. Am Clin Lab 20:42–4PubMedGoogle Scholar
  66. 66.
    Rangel-Frausto MS, Wiblin T, Blumberg HM, Salman L, Patterson J, Rinaldi M, Pfaller M, Edwards JE Jr, Jarvis W, Dawson J, Wenzel RP, NEMIS Study Group (1999) National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units. Clin Infect Dis 29:253–258PubMedGoogle Scholar
  67. 67.
    Reidel K, Hentzer M, Geisenberger O, Huber B, Steidle A, Wu H, Hoiby N, Givskov M, Molin S, Eberl L (2001) N-acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms. Microbiology 147:3249–3262PubMedGoogle Scholar
  68. 68.
    Ren, D, Sims JJ, Wood TK (2001) Inhibition of biofilm formation and swarming of Escherichia coli by (5Z)-4-bromo-5-(bromomethylene-3-butyl-2(5H)-furanone. Environ Microbiol 3:731–736CrossRefPubMedGoogle Scholar
  69. 69.
    Ren D, Zuo R, Wood TK (2004) Quorum-sensing antagonist (5Z)-4-bromo-5-(bromomethylene-3-butyl-2(5H)-furanone influences siderophore biosynthesis in Pseudomonas putida andPseudomonas aeruginosa. Appl Microbiol Biotechnol 65Google Scholar
  70. 70.
    Richards MJ, Edwards JR, Culver DH, Grimes RP (1999) Nosocomial infections in medical intensive care units in the United States: national nosocomial infections surveillance system. Crit Care Med 27:887–892CrossRefPubMedGoogle Scholar
  71. 71.
    Singh PK, Parsek MR, Greenberg EP, Welsh MJ (2002) A component of innate immunity prevents bacterial biofilm development. Nature 417:552–555CrossRefPubMedGoogle Scholar
  72. 72.
    Trautner BW, Darouiche RO (2004) Role of biofilm in catheter-associated urinary tract infection. Am J Infect Control 32:177–183CrossRefPubMedGoogle Scholar
  73. 73.
    Valles J, Mariscal D, Cortes P, Coll P, Villagra A, Diaz E, Artigas A, Rello J (2004) Patterns of colonization by Pseudomonas aeruginosa in intubated patients: a 3-year prospective study of 1,607 isolates using pulsed-field gel electrophoresis with implications for prevention of ventilator-associated pneumonia. Duke University, Durham, N.C.Google Scholar
  74. 74.
    Walder B, Pittet D, Tramer MR (2002) Prevention of bloodstream infections with central venous catheters treated with anti-infective agents depends on catheter type and insertion time: evidence from a meta-analysis. Infect Control Hosp Epidemiol 23:748–756PubMedGoogle Scholar
  75. 75.
    Wingard JR, Merez WG, Rinaldi MG, Johnson TR, Karp JE, Saral R (1991) Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med 325:1274–1277PubMedGoogle Scholar
  76. 76.
    Wingard JR, Merez WG, Rinaldi MG, Johnson TR, Miller CB, Karp JE, Saral R (1993) Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. Antimicrob Agents Chemother 37:1847–1849PubMedGoogle Scholar
  77. 77.
    Wong ES (2004) Guideline for prevention of catheter-associated urinary tract infections. CDC, Washington, D.C.Google Scholar
  78. 78.
    Yang Y-L, Ho Y-A, Cheng H-H, Ho M, Lo H-J (2004) Susceptibilities of Candida species to amphotericin B and fluconazole: the emergence of fluconazole resistance in Candida tropicalis. Infect Control Hosp Epidemiol 25:60–64PubMedGoogle Scholar

Copyright information

© Society for Industrial Microbiology 2005

Authors and Affiliations

  1. 1.Department of BiologyGeorgia State UniversityAtlantaUSA

Personalised recommendations