Abstract
Over the past century, Pseudomonas aeruginosa has become an increasingly important pathogen, particularly in individuals with cystic fibrosis and in intensive care units worldwide. P. aeruginosa possesses a diverse array of virulence factors as well as high intrinsic resistance to many therapeutically-available antibiotics, lending to the characteristically high levels of lethality and persistence associated with P. aeruginosa infections. Furthermore, this bacterium has an unparalleled ability to adapt to the varying environments and stresses it encounters, as its large genome encodes numerous complex regulatory systems, and it readily acquires mobile genetic elements and plasmids. The finely tuned regulation of its virulence factors is best evidenced by the adaptations occurring during chronic cystic fibrosis infections, which contribute to the organism’s ability to evade attack by host immune responses and also limits killing by all available antibiotics. Despite the major role this organism plays within the hospital, few effective antimicrobial agents with adequate anti-pseudomonal activity have been developed and resistance to all available agents has been reported.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Altoparlak U, Erol S, Akcay MN et al (2004) The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns 30:660–664
Ambrose PG, Owens RC Jr, Garvey MJ et al (2002) Pharmacodynamic considerations in the treatment of moderate to severe pseudomonal infections with cefepime. J Antimicrob Chemother 49:445–453
Andriole VT (1971) Synergy of carbenicillin and gentamicin in experimental infection with Pseudomonas. J Infect Dis 124(Suppl):S46–S55
Arora SK, Ritchings BW, Almira EC et al (1998) The Pseudomonas aeruginosa flagellar cap protein, FliD, is responsible for mucin adhesion. Infect Immun 66:1000–1007
Backhed F, Normark S, Schweda EK et al (2003) Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications. Microbes Infect 5:1057–1063
Baker CC, Miller CL, Trunkey DD (1979) Predicting fatal sepsis in burn patients. J Trauma 19:641–648
Bals R, Weiner DJ, Wilson JM (1999) The innate immune system in cystic fibrosis lung disease. J Clin Invest 103:303–307
Bang RL, Sharma PN, Sanyal SC et al (2002) Septicaemia after burn injury: a comparative study. Burns 28:746–751
Barbieri JT, Sun J (2004) Pseudomonas aeruginosa ExoS and ExoT. Rev Physiol Biochem Pharmacol 152:79–92
Barclay ML, Begg EJ, Chambers ST et al (1996) Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis. J Antimicrob Chemother 37: 1155–1164
Barken KB, Pamp SJ, Yang L et al (2008) Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms. Environ Microbiol 10:2331–2343
Barker AF, Couch L, Fiel SB et al (2000) Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 162:481–485
Barret JP, Herndon DN (2003) Effects of burn wound excision on bacterial colonization and invasion. Plast Reconstr Surg 111:744–750, Discussion 51–2
Barrow RE, Spies M, Barrow LN et al (2004) Influence of demographics and inhalation injury on burn mortality in children. Burns 30:72–77
Bellido F, Martin NL, Siehnel RJ et al (1992) Reevaluation, using intact cells, of the exclusion limit and role of porin OprF in Pseudomonas aeruginosa outer membrane permeability. J Bacteriol 174:5196–5203
Beno P, Krcmery V, Demitrovicova A (2006) Bacteraemia in cancer patients caused by colistin-resistant Gram-negative bacilli after previous exposure to ciprofloxacin and/or colistin. Clin Microbiol Infect 12:497–498
Blohmke CJ, Victor RE, Hirschfeld AF et al (2008) Innate immunity mediated by TLR5 as a novel antiinflammatory target for cystic fibrosis lung disease. J Immunol 180:7764–7773
Blondel-Hill E, Fryters S (2006) Bugs and drugs. Capital Health, Edmonton
Bodey GP (1970) Epidemiological studies of Pseudomonas species in patients with leukemia. Am J Med Sci 260:82–89
Bodey GP, Whitecar JP Jr, Middleman E et al (1971) Carbenicillin therapy for pseudomonas infections. J Am Med Assoc 218:62–66
Bodey GP, Jadeja L, Elting L (1985) Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med 145:1621–1629
Boucher JC, Yu H, Mudd MH et al (1997) Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection. Infect Immun 65:3838–3846
Boucher JC, Schurr MJ, Yu H et al (1997) Pseudomonas aeruginosa in cystic fibrosis: role of mucC in the regulation of alginate production and stress sensitivity. Microbiology 143(Pt 11):3473–3480
Bradley DE (1980) A function of Pseudomonas aeruginosa PAO polar pili: twitching motility. Can J Microbiol 26:146–154
Brazas MD, Hancock REW (2005) Ciprofloxacin induction of a susceptibility determinant in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:3222–3227
Breidenstein EBM, Khaira BK, Wiegand I et al (2008) Complex ciprofloxacin resistome revealed by screening a Pseudomonas aeruginosa mutant library for altered susceptibility. Antimicrob Agents Chemother 52:4486–4491
Brint JM, Ohman DE (1995) Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer-responsive LuxR-LuxI family. J Bacteriol 177:7155–7163
Brown MR, Allison DG, Gilbert P (1988) Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? J Antimicrob Chemother 22:777–780
Canton R, Cobos N, de Gracia J et al (2005) Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Clin Microbiol Infect 11:690–703
Cardany CR, Rodeheaver GT, Horowitz JH et al (1985) Influence of hydrotherapy and antiseptic agents on burn wound bacterial contamination. J Burn Care Rehabil 6:230–232
Chamot E, Boffi El Amari E, Rohner P et al (2003) Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia. Antimicrob Agents Chemother 47: 2756–2764
Chastre J (2008) Evolving problems with resistant pathogens. Clin Microbiol Infect 14(Suppl 3): 3–14
Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903
Cheer SM, Waugh J, Noble S (2003) Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Drugs 63:2501–2520
Choong S, Whitfield H (2000) Biofilms and their role in infections in urology. BJU Int 86: 935–941
Church D, Elsayed S, Reid O et al (2006) Burn wound infections. Clin Microbiol Rev 19: 403–434
Collins FS (1992) Cystic fibrosis: molecular biology and therapeutic implications. Science 256:774–779
Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322
Craig W (1993) Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. Eur J Clin Microbiol Infect Dis 12(Suppl 1):S6–S8
Cryz SJ Jr, Furer E, Germanier R (1983) Simple model for the study of Pseudomonas aeruginosa infections in leukopenic mice. Infect Immun 39:1067–1071
Dasgupta N, Wolfgang MC, Goodman AL et al (2003) A four-tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa. Mol Microbiol 50:809–824
Davies JC (2002) Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatr Respir Rev 3:128–134
Deretic V, Schurr MJ, Boucher JC et al (1994) Conversion of Pseudomonas aeruginosa to mucoidy in cystic fibrosis: environmental stress and regulation of bacterial virulence by alternative sigma factors. J Bacteriol 176:2773–2780
Dhand R (2007) The role of aerosolized antimicrobials in the treatment of ventilator-associated pneumonia. Respir Care 52:866–884
Diaz MH, Shaver CM, King JD et al (2008) Pseudomonas aeruginosa induces localized immunosuppression during pneumonia. Infect Immun 76:4414–4421
Diggle SP, Cornelis P, Williams P et al (2006) 4-quinolone signalling in Pseudomonas aeruginosa: old molecules, new perspectives. Int J Med Microbiol 296:83–91
Doggett RG (1969) Incidence of mucoid Pseudomonas aeruginosa from clinical sources. Appl Microbiol 18:936–937
Doggett RG (1979) Microbiology of Pseudomonas aeruginosa. In: Doggett RG (ed) Pseudomonas aeruginosa: clinical manifestations of infection and current therapy. Academic, New York
Doggett RG, Harrison GM, Carter RE (1971) Mucoid Pseudomonas aeruginosa in patients with chronic illnesses. Lancet 1:236–237
Doi Y, Arakawa Y (2007) 16 S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin Infect Dis 45:88–94
Doring G, Pier GB (2008) Vaccines and immunotherapy against Pseudomonas aeruginosa. Vaccine 26:1011–1024
Doring G, Conway SP, Heijerman HG et al (2000) Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16:749–767
Drobnic ME, Sune P, Montoro JB et al (2005) Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother 39:39–44
Dropulic LK, Leslie JM, Eldred LJ et al (1995) Clinical manifestations and risk factors of Pseudomonas aeruginosa infection in patients with AIDS. J Infect Dis 171:930–937
Dudley MN, Zinner SH (1991) Single daily dosing of amikacin in an in-vitro model. J Antimicrob Chemother 27(Suppl C):15–19
El Solh AA, Akinnusi ME, Wiener-Kronish JP et al (2008) Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia. Am J Respir Crit Care Med 178:513–519
Ernst RK, Yi EC, Guo L et al (1999) Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 286:1561–1565
Ernst RK, Hajjar AM, Tsai JH et al (2003) Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4. J Endotoxin Res 9:395–400
Fagon JY, Chastre J, Hance AJ et al (1993) Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med 94:281–288
Falagas ME, Siempos II, Bliziotis IA et al (2006) Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials. Crit Care 10:R123
Faure K, Fujimoto J, Shimabukuro DW et al (2003) Effects of monoclonal anti-PcrV antibody on Pseudomonas aeruginosa-induced acute lung injury in a rat model. J Immune Based Ther Vaccines 1:2
Feeley TW, Du Moulin GC, Hedley-Whyte J et al (1975) Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med 293:471–475
Fishman LS, Armstrong D (1972) Pseudomonas aeruginosa bacteremia in patients with neoplastic disease. Cancer 30:764–773
Frank DW (1997) The exoenzyme S regulon of Pseudomonas aeruginosa. Mol Microbiol 26: 621–629
Frederiksen B, Koch C, Hoiby N (1997) Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 23:330–335
Friedman L, Kolter R (2004) Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol Microbiol 51:675–690
Fukuda H, Hosaka M, Iyobe S et al (1995) nfxC-type quinolone resistance in a clinical isolate of Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:790–792
Fuqua C, Greenberg EP (2002) Listening in on bacteria: acyl-homoserine lactone signalling. Nat Rev Mol Cell Biol 3:685–695
Gacesa P, Wusteman FS (1990) Plate assay for simultaneous detection of alginate lyases and determination of substrate specificity. Appl Environ Microbiol 56:2265–2267
Galloway DR (1991) Pseudomonas aeruginosa elastase and elastolysis revisited: recent developments. Mol Microbiol 5:2315–2321
Gang RK, Bang RL, Sanyal SC et al (1999) Pseudomonas aeruginosa septicaemia in burns. Burns 25:611–616
Gaynes R, Edwards JR (2005) Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 41:848–854
Gibson RL, Burns JL, Ramsey BW (2003) Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 168:918–951
Gibson RL, Emerson J, McNamara S et al (2003) Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Respir Crit Care Med 167:841–849
Gilleland LB, Gilleland HE, Gibson JA et al (1989) Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa. J Med Microbiol 29:41–50
Goranson J, Hovey AK, Frank DW (1997) Functional analysis of exsC and exsB in regulation of exoenzyme S production by Pseudomonas aeruginosa. J Bacteriol 179:1646–1654
Gotoh N, Itoh N, Tsujimoto H et al (1994) Isolation of OprM-deficient mutants of Pseudomonas aeruginosa by transposon insertion mutagenesis: evidence of involvement in multiple antibiotic resistance. FEMS Microbiol Lett 122:267–273
Govan JR, Deretic V (1996) Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 60:539–574
Grassme H, Jendrossek V, Riehle A et al (2003) Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat Med 9:322–330
Grimwood K (1992) The pathogenesis of Pseudomonas aeruginosa lung infections in cystic fibrosis. J Paediatr Child Health 28:4–11
Hahn HP (1997) The type-4 pilus is the major virulence-associated adhesin of Pseudomonas aeruginosa–a review. Gene 192:99–108
Hancock REW (1997) The bacterial outer membrane as a drug barrier. Trends Microbiol 5:37–42
Hancock REW (1998) Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin Infect Dis 27(Suppl 1):S93–S99
Hancock REW, Woodruff WA (1988) Roles of porin and beta-lactamase in beta-lactam resistance of Pseudomonas aeruginosa. Rev Infect Dis 10:770–775
Hancock REW, Raffle VJ, Nicas TI (1981) Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother 19:777–785
Hancock REW, Mutharia LM, Chan L et al (1983) Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun 42:170–177
Hanessian S, Regan W, Watson D et al (1971) Isolation and characterization of antigenic components of a new heptavalent Pseudomonas vaccine. Nat New Biol 229:209–210
Hansen JK, Forest KT (2006) Type IV pilin structures: insights on shared architecture, fiber assembly, receptor binding and type II secretion. J Mol Microbiol Biotechnol 11:192–207
Hansen M, Christrup LL, Jarlov JO et al (2001) Gentamicin dosing in critically ill patients. Acta Anaesthesiol Scand 45:734–740
Hauser AR, Cobb E, Bodi M et al (2002) Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med 30:521–528
Haussler S, Ziegler I, Lottel A et al (2003) Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. J Med Microbiol 52:295–301
Heine H, Rietschel ET, Ulmer AJ (2001) The biology of endotoxin. Mol Biotechnol 19:279–296
Henrichfreise B, Wiegand I, Pfister W et al (2007) Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation. Antimicrob Agents Chemother 51:4062–4070
Heurlier K, Williams F, Heeb S et al (2004) Positive control of swarming, rhamnolipid synthesis, and lipase production by the posttranscriptional RsmA/RsmZ system in Pseudomonas aeruginosa PAO1. J Bacteriol 186:2936–2945
Hidron AI, Edwards JR, Patel J et al (2008) NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 29:996–1011
Hilf M, Yu VL, Sharp J et al (1989) Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 87:540–546
Hodson ME (2000) Treatment of cystic fibrosis in the adult. Respiration 67:595–607
Hodson ME, Penketh AR, Batten JC (1981) Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. Lancet 2:1137–1139
Hoffmann N, Rasmussen TB, Jensen PO et al (2005) Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect Immun 73: 2504–2514
Hoffmann N, Lee B, Hentzer M et al (2007) Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Pseudomonas aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr(−/−) mice. Antimicrob Agents Chemother 51:3677–3687
Hogardt M, Hoboth C, Schmoldt S et al (2007) Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 195:70–80
Hoiby N (1998) Pseudomonas in cystic fibrosis: past, present, and future. Cystic Fibrosis Trust, London
Hollsing AE, Granstrom M, Vasil ML et al (1987) Prospective study of serum antibodies to Pseudomonas aeruginosa exoproteins in cystic fibrosis. J Clin Microbiol 25:1868–1874
Holmes KK, Clark H, Silverblatt F et al (1969) Emergence of resistance in Pseudomonas during carbenicillin therapy. Antimicrob Agents Chemother (Bethesda) 9:391–397
Hoyle BD, Costerton JW (1991) Bacterial resistance to antibiotics: the role of biofilms. Prog Drug Res 37:91–105
Hoyle BD, Jass J, Costerton JW (1990) The biofilm glycocalyx as a resistance factor. J Antimicrob Chemother 26:1–5
Huang H, Hancock REW (1993) Genetic definition of the substrate selectivity of outer membrane porin protein OprD of Pseudomonas aeruginosa. J Bacteriol 175:7793–7800
Huang H, Hancock REW (1996) The role of specific surface loop regions in determining the function of the imipenem-specific pore protein OprD of Pseudomonas aeruginosa. J Bacteriol 178:3085–3090
Hudson VL, Wielinski CL, Regelmann WE (1993) Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years. J Pediatr 122:854–860
Jagger KS, Robinson DL, Franz MN et al (1982) Detection by enzyme-linked immunosorbent assays of antibody specific for Pseudomonas proteases and exotoxin A in sera from cystic fibrosis patients. J Clin Microbiol 15:1054–1058
Jalal S, Wretlind B (1998) Mechanisms of quinolone resistance in clinical strains of Pseudomonas aeruginosa. Microb Drug Resist 4:257–261
Jo JT, Brinkman FS, Hancock REW (2003) Aminoglycoside efflux in Pseudomonas aeruginosa: involvement of novel outer membrane proteins. Antimicrob Agents Chemother 47: 1101–1111
Khoury AE, Lam K, Ellis B et al (1992) Prevention and control of bacterial infections associated with medical devices. ASAIO J 38:M174–M178
Kirisits MJ, Prost L, Starkey M et al (2005) Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 71:4809–4821
Klausen M, Aaes-Jorgensen A, Molin S et al (2003) Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol Microbiol 50:61–68
Klausen M, Heydorn A, Ragas P et al (2003) Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol Microbiol 48:1511–1524
Knirel YA, Bystrova OV, Shashkov AS et al (2001) Structural analysis of the lipopolysaccharide core of a rough, cystic fibrosis isolate of Pseudomonas aeruginosa. Eur J Biochem 268:4708–4719
Knirel YA, Bystrova OV, Kocharova NA et al (2006) Conserved and variable structural features in the lipopolysaccharide of Pseudomonas aeruginosa. J Endotoxin Res 12:324–336
Kobayashi M, Yoshida T, Takeuchi D et al (2008) Gr-1(+)CD11b(+) cells as an accelerator of sepsis stemming from Pseudomonas aeruginosa wound infection in thermally injured mice. J Leukoc Biol 83:1354–1362
Kohler T, Michea-Hamzehpour M, Plesiat P et al (1997) Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 41:2540–2543
Kohler T, Curty LK, Barja F et al (2000) Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182:5990–5996
Kurahashi K, Kajikawa O, Sawa T et al (1999) Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 104:743–750
Kus JV, Tullis E, Cvitkovitch DG et al (2004) Significant differences in type IV pilin allele distribution among Pseudomonas aeruginosa isolates from cystic fibrosis (CF) versus non-CF patients. Microbiology 150:1315–1326
Lam JS, Lam MY, MacDonald LA et al (1987) Visualization of Pseudomonas aeruginosa O antigens by using a protein A-dextran-colloidal gold conjugate with both immunoglobulin G and immunoglobulin M monoclonal antibodies. J Bacteriol 169:3531–3538
Langaee TY, Dargis M, Huletsky A (1998) An ampD gene in Pseudomonas aeruginosa encodes a negative regulator of AmpC beta-lactamase expression. Antimicrob Agents Chemother 42:3296–3300
Langford DT, Hiller J (1984) Prospective, controlled study of a polyvalent Pseudomonas vaccine in cystic fibrosis–three year results. Arch Dis Child 59:1131–1134
Le Conte P, Potel G, Peltier P et al (1993) Lung distribution and pharmacokinetics of aerosolized tobramycin. Am Rev Respir Dis 147:1279–1282
Leibovici L, Paul M (2007) Aminoglycoside/beta-lactam combinations in clinical practice. J Antimicrob Chemother 60:911–912
Leibovici L, Paul M, Poznanski O et al (1997) Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study. Antimicrob Agents Chemother 41:1127–1133
Li XZ, Nikaido H, Poole K (1995) Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:1948–1953
Littlewood JM, Miller MG, Ghoneim AT et al (1985) Nebulised colomycin for early pseudomonas colonisation in cystic fibrosis. Lancet 1:865
Liu PV, Wang S (1990) Three new major somatic antigens of Pseudomonas aeruginosa. J Clin Microbiol 28:922–925
Livermore DM (1987) Clinical significance of beta-lactamase induction and stable derepression in gram-negative rods. Eur J Clin Microbiol 6:439–445
Llanes C, Hocquet D, Vogne C et al (2004) Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob Agents Chemother 48:1797–1802
Lodge J, Busby S, Piddock L (1993) Investigation of the Pseudomonas aeruginosa ampR gene and its role at the chromosomal ampC beta-lactamase promoter. FEMS Microbiol Lett 111:315–320
MacMillan BG (1980) Infections following burn injury. Surg Clin North Am 60:185–196
Mah TF, Pitts B, Pellock B et al (2003) A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426:306–310
Masuda N, Sakagawa E, Ohya S (1995) Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 39:645–649
Masuda N, Sakagawa E, Ohya S et al (2000) Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:3322–3327
Masuda N, Sakagawa E, Ohya S et al (2000) Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 44:2242–2246
McCall CY, Spruill WJ, Wade WE (1989) The use of aerosolized tobramycin in the treatment of a resistant pseudomonal pneumonitis. Ther Drug Monit 11:692–695
McCoy KS, Quittner AL, Oermann CM et al (2008) Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med 178: 921–928
Morrison AJ Jr, Wenzel RP (1984) Epidemiology of infections due to Pseudomonas aeruginosa. Rev Infect Dis 6(Suppl 3):S627–S642
Moskowitz SM, Ernst RK, Miller SI (2004) PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 186:575–579
Nicas TI, Hancock REW (1983) Alteration of susceptibility to EDTA, polymyxin B and gentamicin in Pseudomonas aeruginosa by divalent cation regulation of outer membrane protein H1. J Gen Microbiol 129:509–517
Nikaido H (2001) Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria. Semin Cell Dev Biol 12:215–223
Nikaido H, Nikaido K, Harayama S (1991) Identification and characterization of porins in Pseudomonas aeruginosa. J Biol Chem 266:770–779
Nixon GM, Armstrong DS, Carzino R et al (2001) Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. J Pediatr 138:699–704
NNIS (2004) National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 32:470–485
Ochs MM, McCusker MP, Bains M et al (1999) Negative regulation of the Pseudomonas aeruginosa outer membrane porin OprD selective for imipenem and basic amino acids. Antimicrob Agents Chemother 43:1085–1090
Oliver A, Canton R, Campo P et al (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–1254
Orriols R, Roig J, Ferrer J et al (1999) Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa. Respir Med 93:476–480
Pai H, Kim J, Lee JH et al (2001) Carbapenem resistance mechanisms in Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 45:480–484
Palmer LB, Smaldone GC, Simon SR et al (1998) Aerosolized antibiotics in mechanically ventilated patients: delivery and response. Crit Care Med 26:31–39
Passador L, Iglewski W (1994) ADP-ribosylating toxins. Methods Enzymol 235:617–631
Paul M, Leibovici L (2005) Combination antibiotic therapy for Pseudomonas aeruginosa bacteraemia. Lancet Infect Dis 5:192–193, Discussion 3–4
Pennington JE (1979) Lipopolysaccharide Pseudomonas vaccine: efficacy against pulmonary infection with Pseudomonas aeruginosa. J Infect Dis 140:73–80
Pennington JE (1981) Penetration of antibiotics into respiratory secretions. Rev Infect Dis 3:67–73
Pennington JE, Miler JJ (1979) Evaluation of a new polyvalent Pseudomonas vaccine in respiratory infections. Infect Immun 25:1029–1034
Pier GB (2007) Pseudomonas aeruginosa lipopolysaccharide: a major virulence factor, initiator of inflammation and target for effective immunity. Int J Med Microbiol 297:277–295
Pier GB, Ames P (1984) Mediation of the killing of rough, mucoid isolates of Pseudomonas aeruginosa from patients with cystic fibrosis by the alternative pathway of complement. J Infect Dis 150:223–228
Pier GB, Ramphal R (2005) Pseudomonas aeruginosa. In: Mandell GL, Bennett JE (eds) Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Elsevier/Churchill Livingstone, New York
Pier GB, Coleman F, Grout M et al (2001) Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis. Infect Immun 69:1895–1901
Poole K, Gotoh N, Tsujimoto H et al (1996) Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 21:713–724
Punsalang AP Jr, Sawyer WD (1973) Role of pili in the virulence of Neisseria gonorrhoeae. Infect Immun 8:255–263
Ramphal R, Guay C, Pier GB (1987) Pseudomonas aeruginosa adhesins for tracheobronchial mucin. Infect Immun 55:600–603
Ramsey BW, Pepe MS, Quan JM et al (1999) Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic fibrosis inhaled tobramycin study group. N Engl J Med 340:23–30
Rasmussen TB, Givskov M (2006) Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296:149–161
Ratjen F, Doring G (2003) Cystic fibrosis. Lancet 361:681–689
Ratjen F, Doring G, Nikolaizik WH (2001) Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Lancet 358:983–984
Ratjen F, Comes G, Paul K et al (2001) Effect of continuous antistaphylococcal therapy on the rate of P. aeruginosa acquisition in patients with cystic fibrosis. Pediatr Pulmonol 31: 13–16
Reimmann C, Beyeler M, Latifi A et al (1997) The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24:309–319
Rello J, Ausina V, Ricart M et al (1993) Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 104:1230–1235
Richmond MH, Sykes RB (1973) The beta-lactamases of gram-negative bacteria and their possible physiological role. Adv Microb Physiol 9:31–88
Rosenfeld M, Ramsey BW, Gibson RL (2003) Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. Curr Opin Pulm Med 9:492–497
Ryder C, Byrd M, Wozniak DJ (2007) Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr Opin Microbiol 10:644–648
Sabath LD (1984) Biochemical and physiologic basis for susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents. Rev Infect Dis 6(Suppl 3):S643–S656
Sacha P, Wieczorek P, Hauschild T et al (2008) Metallo-beta-lactamases of Pseudomonas aeruginosa–a novel mechanism resistance to beta-lactam antibiotics. Folia Histochem Cytobiol 46:137–142
Saiman L, Marshall BC, Mayer-Hamblett N et al (2003) Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. J Am Med Assoc 290:1749–1756
Salunkhe P, Smart CH, Morgan JA et al (2005) A cystic fibrosis epidemic strain of Pseudomonas aeruginosa displays enhanced virulence and antimicrobial resistance. J Bacteriol 187:4908–4920
Sanders CC (1992) Beta-lactamases of gram-negative bacteria: new challenges for new drugs. Clin Infect Dis 14:1089–1099
Sato H, Frank DW (2004) ExoU is a potent intracellular phospholipase. Mol Microbiol 53:1279–1290
Sauer K, Camper AK, Ehrlich GD et al (2002) Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 184:1140–1154
Schimpff S, Satterlee W, Young VM et al (1971) Empiric therapy with carbenicillin and Âgentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med 284: 1061–1065
Schultz MJ, Rijneveld AW, Florquin S et al (2002) Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia. Am J Physiol Lung Cell Mol Physiol 282:L285–L290
Schurek KN, Marr AK, Taylor PK et al (2008) Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 52: 4213–4219
Scott RE, Robson HG (1976) Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats. Antimicrob Agents Chemother 10: 646–651
Shaw KJ, Rather PN, Hare RS et al (1993) Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev 57:138–163
Shawar RM, MacLeod DL, Garber RL et al (1999) Activities of tobramycin and six other antibiotics against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 43:2877–2880
Shime N, Sawa T, Fujimoto J et al (2001) Therapeutic administration of anti-PcrV F(ab′)(2) in sepsis associated with Pseudomonas aeruginosa. J Immunol 167:5880–5886
Singh PK, Schaefer AL, Parsek MR et al (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407:762–764
Smith AL, Doershuk C, Goldmann D et al (1999) Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis. J Pediatr 134:413–421
Smith RS, Harris SG, Phipps R et al (2002) The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 184:1132–1139
Sorensen VJ, Horst HM, Obeid FN et al (1986) Endotracheal aminoglycosides in gram negative pneumonia. A preliminary report. Am Surg 52:391–394
Souli M, Galani I, Giamarellou H (2008) Emergence of extensively drug-resistant and pandrug-resistant Gram-negative bacilli in Europe. Euro Surveill 13 (47) pii:19045
Spoering AL, Lewis K (2001) Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 183:6746–6751
Starner TD, McCray PB Jr (2005) Pathogenesis of early lung disease in cystic fibrosis: a window of opportunity to eradicate bacteria. Ann Intern Med 143:816–822
Stead RJ, Hodson ME, Batten JC (1987) Inhaled ceftazidime compared with gentamicin and carbenicillin in older patients with cystic fibrosis infected with Pseudomonas aeruginosa. Br J Dis Chest 81:272–279
Steinkamp G, Tummler B, Gappa M et al (1989) Long-term tobramycin aerosol therapy in cystic fibrosis. Pediatr Pulmonol 6:91–98
Stieritz DD, Holder IA (1975) Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: description of a burned mouse model. J Infect Dis 131:688–691
Stillwell PC, Kearns GL, Jacobs RF (1988) Endotracheal tobramycin in gram-negative pneumonitis. Drug Intell Clin Pharm 22:577–581
Stoutenbeek CP, van Saene HK, Miranda DR et al (1986) Nosocomial gram-negative pneumonia in critically ill patients. A 3-year experience with a novel therapeutic regimen. Intensive Care Med 12:419–423
Stover CK, Pham XQ, Erwin AL et al (2000) Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406:959–964
Sykes RB, Matthew M (1976) The beta-lactamases of gram-negative bacteria and their role in resistance to beta-lactam antibiotics. J Antimicrob Chemother 2:115–157
Taccetti G, Campana S, Festini F et al (2005) Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients. Eur Respir J 26:458–461
Takada H, Kotani S (1989) Structural requirements of lipid A for endotoxicity and other biological activities. Crit Rev Microbiol 16:477–523
Tart AH, Wolfgang MC, Wozniak DJ (2005) The alternative sigma factor AlgT represses Pseudomonas aeruginosa flagellum biosynthesis by inhibiting expression of fleQ. J Bacteriol 187:7955–7962
Tateda K, Comte R, Pechere JC et al (2001) Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother 45:1930–1933
Tateda K, Standiford TJ, Pechere JC et al (2004) Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors. Curr Pharm Des 10:3055–3065
Trafny EA (1998) Susceptibility of adherent organisms from Pseudomonas aeruginosa and Staphylococcus aureus strains isolated from burn wounds to antimicrobial agents. Int J Antimicrob Agents 10:223–228
Treggiari MM, Rosenfeld M, Retsch-Bogart G et al (2007) Approach to eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Pediatr Pulmonol 42:751–756
Valcke Y, Pauwels R, Van der Straeten M (1990) Pharmacokinetics of antibiotics in the lungs. Eur Respir J 3:715–722
Valerius NH, Koch C, Hoiby N (1991) Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 338:725–726
van Hartingsveldt J, Stouthamer AH (1973) Mapping and characerization of mutants of Pseudomonas aeruginosa affected in nitrate respiration in aerobic or anaerobic growth. J Gen Microbiol 74:97–106
Verhagen C, de Pauw BE, Donnelly JP et al (1986) Ceftazidime alone for treating Pseudomonas aeruginosa septicaemia in neutropenic patients. J Infect 13:125–131
Verma A, Arora SK, Kuravi SK et al (2005) Roles of specific amino acids in the N terminus of Pseudomonas aeruginosa flagellin and of flagellin glycosylation in the innate immune response. Infect Immun 73:8237–8246
Westbrock-Wadman S, Sherman DR, Hickey MJ et al (1999) Characterization of a Pseudomonas aeruginosa efflux pump contributing to aminoglycoside impermeability. Antimicrob Agents Chemother 43:2975–2983
Whitecar JP Jr, Luna M, Bodey GP (1970) Pseudomonas bacteremia in patients with malignant diseases. Am J Med Sci 60:216–223
Winstanley C, Fothergill JL (2009) The role of quorum sensing in chronic cystic fibrosis Pseudomonas aeruginosa infections. FEMS Microbiol Lett 290:1–9
Yahr TL, Mende-Mueller LM, Friese MB et al (1997) Identification of type III secreted products of the Pseudomonas aeruginosa exoenzyme S regulon. J Bacteriol 179:7165–7168
Yahr TL, Vallis AJ, Hancock MK et al (1998) ExoY, an adenylate cyclase secreted by the Pseudomonas aeruginosa type III system. Proc Natl Acad Sci USA 95:13899–13904
Zhuo H, Yang K, Lynch SV et al (2008) Increased mortality of ventilated patients with endotracheal Pseudomonas aeruginosa without clinical signs of infection. Crit Care Med 36: 2495–2503
Ziha-Zarifi I, Llanes C, Kohler T et al (1999) In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Antimicrob Agents Chemother 43:287–291
Acknowledgments
We would like to thank the Canadian Institutes of Health Research as well as Cystic Fibrosis Canada for supporting our work. Furthermore, K.N.S. holds a Natural Sciences and Engineering Council of Canada postgraduate scholarship and a Michael Smith Foundation for Health Research Senior graduate studentship. E.B.M.B. is a recipient of a scholarship from Cystic Fibrosis Canada. R.E.W.H. holds a Canada Research Chair.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Schurek, K.N., Breidenstein, E.B.M., Hancock, R.E.W. (2012). Pseudomonas aeruginosa: A Persistent Pathogen in Cystic Fibrosis and Hospital-Associated Infections. In: Dougherty, T., Pucci, M. (eds) Antibiotic Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1400-1_21
Download citation
DOI: https://doi.org/10.1007/978-1-4614-1400-1_21
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-1399-8
Online ISBN: 978-1-4614-1400-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)