Intensive Care Medicine

, Volume 35, Issue 3, pp 439–447

Influence of antipseudomonal agents on Pseudomonas aeruginosa colonization and acquisition of resistance in critically ill medical patients

  • José A. Martínez
  • Esther Delgado
  • Sara Martí
  • Francesc Marco
  • Jordi Vila
  • Josep Mensa
  • Antoni Torres
  • Carles Codina
  • Antoni Trilla
  • Alex Soriano
  • Aitor Alquezar
  • Pedro Castro
  • José M. Nicolás



To assess the role of antipseudomonal agents on Pseudomonasaeruginosa colonization and acquisition of resistance.


Prospective cohort study.


Two medical intensive care units.

Patients and participants

346 patients admitted for ≥ 48 h.


Analysis of data from an 8-month study comparing a mixing versus a cycling strategy of antibiotic use.

Measurements and results

Surveillance cultures from nares, pharynx, rectum, and respiratory secretions were obtained thrice weekly. Acquisition of resistance was defined as the isolation, after 48 h of ICU stay, of an isolate resistant to a given antibiotic if culture of admission samples were either negative or positive for a susceptible isolate. Emergence of resistance refers to the conversion of a defined pulsotype from susceptible to non-susceptible. Forty-four (13%) patients acquired 52 strains of P. aeruginosa. Administration of piperacillin-tazobactam for ≥ 3 days (OR 2.6, 95% CI 1.09–6.27) and use of amikacin for ≥ 3 days (OR 2.6, 95% CI 1.04–6.7) were positively associated with acquisition of P. aeruginosa, whereas use of quinolones (OR 0.27, 95% CI 0.1–0.7) and antipseudomonal cephalosporins (OR 0.27, 95% CI 0.08–0.9) was protective. Exposure to quinolones and cephalosporins was not associated with the acquisition of resistance, whereas it was linked with usage of all other agents. Neither quinolones nor cephalosporins were a major determinant on the emergence of resistance to themselves, as resistance to these antibiotics developed at a similar frequency in non-exposed patients.


In critically ill patients, quinolones and antipseudomonal cephalosporins may prevent the acquisition of P. aeruginosa and may have a negligible influence on the acquisition and emergence of resistance.


Intensive care unit Pseudomonas aeruginosa Antipseudomonal agents Antimicrobial resistance Emergence of resistance Nosocomial infection 


  1. 1.
    Vincent JL (2003) Nosocomial infections in adult intensive-care units. Lancet 361:2068–2077PubMedCrossRefGoogle Scholar
  2. 2.
    Bonten MJM, Bergmans DCJJ, Speijer H, Stobberingh EE (1999) Characteristics of polyclonal endemicity of Pseudomonas aeruginosa colonization in intensive care units. Implications for infection control. Am J Respir Crit Care Med 160:1212–1219PubMedGoogle Scholar
  3. 3.
    Lepelletier D, Caroff N, Riochet D, Bizouarn P, Bourdeau A, Le Gallou F, Esparze E, Reynaud A, Richet H (2006) Role of hospital stay and antibiotic use on Pseudomonas aeruginosa gastrointestinal colonization in hospitalized patients. Eur J Clin Microbiol Infect Dis 25:600–603PubMedCrossRefGoogle Scholar
  4. 4.
    Rello J, Ausina V, Ricart M, Castella J, Prats G (1993) Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 104:1230–1235PubMedCrossRefGoogle Scholar
  5. 5.
    Trouillet JL, Chastre J, Vuagnat A, Joly-Guillou ML, Combaux D, Dombret MC, Gibert C (1998) Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med 157:531–539PubMedGoogle Scholar
  6. 6.
    Carmeli Y, Troillet N, Eliopoulos GM, Samore MH (1999) Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 43:1379–1382PubMedGoogle Scholar
  7. 7.
    Fink MP, Snydman DR, Niederman MS, Leeper KV, Johnson RH, Heard SO, Wunderink RG, Caldwell JW, Schentag JJ, Siami GA, Zameck RL, Harverstock DC, Reinhart HH, Echols RM, the Severe Pneumonia Study Group (1994) Treatment of severe pneumonia in hospitalizae patients: result of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob Agents Chemother 38:547–557PubMedGoogle Scholar
  8. 8.
    Zanetti G, Bally F, Greub G, Garbino J, Kinge T, Lew D, Romand JA, Bille J, Aymon D, Stratchounski L, Krawczyk L, Rubinstein E, Schaller MD, Chiolero R, Cometta A, The Cefepime Study Group (2003) Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study. Antimicrob Agents Chemother 47:3442–3447PubMedCrossRefGoogle Scholar
  9. 9.
    Troillet N, Samore MH, Carmeli Y (1997) Imipenem-resistant Pseudomonas aeruginosa: risk factors and antibiotic susceptibility patterns. Clin Infect Dis 25:1094–1098PubMedCrossRefGoogle Scholar
  10. 10.
    El Amari EB, Chamot E, Auckenthaler R, Pechère JC, Van Delden C (2001) Influence of previous exposure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates. Clin Infect Dis 33:1859–1864PubMedCrossRefGoogle Scholar
  11. 11.
    Harris AD, Smith D, Johnson JA, Bradham DD, Roghmann MC (2002) Risk factors for imipenem-resistant Pseudomonas aeruginosa among hospitalized patients. Clin Infect Dis 34:340–345PubMedCrossRefGoogle Scholar
  12. 12.
    Harris AD, Perencevich E, Roghmann MC, Morris G, Kaye KS, Johnson JA (2002) Risk factors for piperacillin-tazobactam-resistant Pseudomonas aeruginosa among hospitalized patients. Antimicrob Agents Chemother 46:854–858PubMedCrossRefGoogle Scholar
  13. 13.
    Paladino JA, Sunderlin JL, Forrest A, Schentag JJ (2003) Characterization of the onset and consequences of pneumonia due to fluoroquinolone-susceptible or resistant Pseudomonas aeruginosa. J Antimicrob Chemother 52:457–463PubMedCrossRefGoogle Scholar
  14. 14.
    Hsu DI, Okamoto MP, Murthy R, Wong-Beringer A (2005) Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition and impact on outcomes. J Antimicrob Chemother 55:535–541PubMedCrossRefGoogle Scholar
  15. 15.
    Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, Oh MD, Choe KW (2005) Risk factors for antimicrobial resistance and influence of resistance on mortality in patients with bloodstream infection caused by Pseudomonas aeruginosa. Microb Drug Resist 11:68–74PubMedCrossRefGoogle Scholar
  16. 16.
    Ozkurt Z, Erteck M, Ero S, Altoparlak U, Akcay MN (2005) The risk for acquisition of imipenem-resistant Pseudomonas aeruginosa in the burn unit. Burn 31:870–873CrossRefGoogle Scholar
  17. 17.
    Zavascki AP, Cruz RP, Goldani LZ (2005) Risk factors for imipenem-resistant Pseudomonas aeruginosa: a comparitive analysis of two case-control studies in hospitalized patients. J Hosp Infect 59:96–101PubMedCrossRefGoogle Scholar
  18. 18.
    Fortaleza CM, Freire MP, Filho Dde C, de Carvalho Ramos M (2006) Risk factors for recovery of imipenem- or ceftazidime-resistant Pseudomonas aeruginosa among patients admitted to a teaching hospital in Brazil. Infect Control Hosp Epidemiol 27:901–906PubMedCrossRefGoogle Scholar
  19. 19.
    Gasink LB, Fishman NO, Weiner MG, Nachmkin I, Bilker WB, Lautehnbach E (2006) Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact. Am J Med 119:526.e19–526.e25CrossRefGoogle Scholar
  20. 20.
    Kaye KS, Kanafani ZA, Dodds AE, Engemann JJ, Weber SG, Carmeli Y (2006) Differential efects of levofloxacin and ciprofloxacin on the risk for isolation of quinolone-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 50:2192–2196PubMedCrossRefGoogle Scholar
  21. 21.
    Peña C, Guzmán A, Suarez C, Dominguez MA, Tubau F, Pujol M, Gudiol F, Ariza J (2007) Effects of carbapenem exposure on the risk for digestive tract carriage of intensive care unit-endemic carbapenem-resistant Pseudomonas aeruginosa strains in critically ill patients. Antimicrob Agents Chemother 51:1967–1971PubMedCrossRefGoogle Scholar
  22. 22.
    Arruda EAG, Marinho IS, Boulos M, Sinto SI, Caiaffa HH, Mendes CM, Oplustil CP, Sader H, Levy CE, Levin AS (1999) Nosocomial infections caused by multiresistant Pseudomonas aeruginosa. Infect Control Hosp Epidemiol 20:620–623PubMedCrossRefGoogle Scholar
  23. 23.
    Cao B, Wang H, Sun H, Zhu Y, Chen M (2004) Risk factors and clinical outcomes of nosocomial multi-drug resistant Pseudomonas aeruginosa infections. J Hosp Infect 57:112–118PubMedCrossRefGoogle Scholar
  24. 24.
    Defez C, Fabbro-Peray P, Bouziges N, Gouby A, Mahamat A, Daurès JP, Sotto A (2004) Risk factors for multidrug-resistant Pseudomonas aeruginosa nosocomial infection. J Hosp Infect 57:209–216PubMedCrossRefGoogle Scholar
  25. 25.
    Lauthenbach E, Weiner MG, Nachamkin I, Bilker WB, Sheridan A, Fishman NO (2006) Imipenem resistance among Pseudomonas aeruginosa isolates: risk factors for infection and impact of resistance on clinical and economic outcomes. Infec Control Hosp Epidemiol 27:893–900CrossRefGoogle Scholar
  26. 26.
    Lee SC, Fung CP, Liu PYF, Wang TC, See LC, Lee N, Chen SC, Shieh WB (1999) Nosocomial infections with ceftazidime-resistant Pseudomonas aeruginosa: risk factors and outcome. Infect Control Hosp Epidemiol 20:205–207PubMedCrossRefGoogle Scholar
  27. 27.
    Ohmagari N, Hanna H, Graviss L, Hackett B, Perego C, Gonzalez V, Dvorak T, Hogan H, Hachem R, Rolston K, Raad I (2005) Risk factors for infections with multidrug-resistant Pseudomonas aeruginosa in patients with cancer. Cancer 104:205–212PubMedCrossRefGoogle Scholar
  28. 28.
    Ortega B, Groeneveld ABJ, Schultsz C (2004) Endemic multidrug-resistant Pseudomonas aeruginosa in critically ill patients. Infect Control Hosp Epìdemiol 25:825–831PubMedCrossRefGoogle Scholar
  29. 29.
    Paramythiotou E, Lucet JC, Timsit JF, Vanjak D, Paugam-Burtz C, Trouillet JL, Belloc S, Kassis N, Karabinis A, Andremont A (2004) Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomoal activity. Clin Infect Dis 38:670–677PubMedCrossRefGoogle Scholar
  30. 30.
    Philippe E, Weiss M, Schultz JM, Yeomans F, Ehrenkranz NJ (1999) Emergence of highly antibiotic-resistant Pseudomonas aeruginosa in relation to duration of empirical antipseudomonal antibiotic treatment. Clin Perform Qual Health Care 7:83–87PubMedGoogle Scholar
  31. 31.
    Trouillet JL, Vuagnat A, Combes A, Kassis N, Chastre J, Gibert C (2002) Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis 34:1047–1054PubMedCrossRefGoogle Scholar
  32. 32.
    Martinez JA, Nicolas JM, Marco F, Horcajada JP, Garcia-Segarra G, Trilla A, Codina C, Torres A, Mensa J (2006) Comparison of antimicrobial cycling and mixing strategies in two medical intensive care units. Crit Care Med 34:329–336PubMedCrossRefGoogle Scholar
  33. 33.
    Clinical and Laboratory Standard Institute. Performance standards for antimicrobial susceptibility testing; sixteenth informational supplement (2006) Document M100-S16. Wayne, PennsylvaniaGoogle Scholar
  34. 34.
    Gautom RK (1997) Rapid pulsed-field gel electrophoresis protocol for typing of Escherichia coli O157:H7 and other gram-negative organisms in 1 day. J Clin Microbiol 35:2977–2980PubMedGoogle Scholar
  35. 35.
    Bonten MJM, Slaugther S, Ambergen AW, Hayden MK, von Voorhis J, Nathan C, Weinstein RA (1998) The role of “colonization pressure” in the spread of vancomycin-resistant enterococci. Arch Intern Med 158:1127–1132PubMedCrossRefGoogle Scholar
  36. 36.
    Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, Allione B, D’Antonio D, Buelli M, Nosari AM, Cilloni D, Zuffa E, Cantaffa R, Specchia G, Amadori S, Fabbiano F, Deliliers GL, Lauria F, Foa R, Del Favero A, Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) Infection Program (2005) Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 353:977–987PubMedCrossRefGoogle Scholar
  37. 37.
    Polk RE, Johnson CK, McClish D, Wenzel RP, Edmond MB (2004) Predicting hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from fluoroquinolone use in US hospitals and their surrounding communities. Clin Infect Dis 39:497–503PubMedCrossRefGoogle Scholar
  38. 38.
    Schwaber MJ, Cosgrove SE, Gold HS, Kaye KS, Carmeli Y (2004) Fluoroquinolones protective against cephalosporin resistance in gram-negative nosocomial pathogens. Em Infect Dis 10:94–99Google Scholar
  39. 39.
    Ziha-Zarifi I, Llanes C, Kohler T, Pechere JC, Plesiat P (1999) In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressin the active efflux system MexA-MexB-OprM. Antimicrob Agents Chemother 43:287–291PubMedGoogle Scholar
  40. 40.
    Bliziotis IA, Samonis G, Vardakas KZ, Chrysanthopoulou S, Falagas ME (2005) Effect of aminoglycoside and beta-lactam combination therapy versus beta-lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials. Clin Infect Dis 41:149–158PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • José A. Martínez
    • 1
  • Esther Delgado
    • 2
  • Sara Martí
    • 3
  • Francesc Marco
    • 3
  • Jordi Vila
    • 3
  • Josep Mensa
    • 1
  • Antoni Torres
    • 4
  • Carles Codina
    • 5
  • Antoni Trilla
    • 6
  • Alex Soriano
    • 1
  • Aitor Alquezar
    • 2
  • Pedro Castro
    • 2
  • José M. Nicolás
    • 2
  1. 1.Department of Infectious DiseasesHospital Clínic, IDIBAPS, University of BarcelonaBarcelonaSpain
  2. 2.Medical Intensive Care UnitHospital Clínic, IDIBAPS, University of BarcelonaBarcelonaSpain
  3. 3.Microbiology LaboratoryHospital Clínic, IDIBAPS, University of BarcelonaBarcelonaSpain
  4. 4.Respiratory Intensive Care Unit-ICPTCHospital Clínic, IDIBAPS, University of BarcelonaBarcelonaSpain
  5. 5.Department of PharmacyHospital Clínic, IDIBAPS, University of BarcelonaBarcelonaSpain
  6. 6.Unit for Evaluation, Supporting and PreventionHospital Clínic, IDIBAPS, University of BarcelonaBarcelonaSpain

Personalised recommendations