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Pharmacokinetics and Pharmacodynamics of Antibiotics in Biofilm Infections of Pseudomonas aeruginosa In Vitro and In Vivo

  • Wang HengzhuangEmail author
  • Niels Høiby
  • Oana Ciofu
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1147)

Abstract

Although progress on biofilm research has been obtained during the past decades, the treatment of biofilm infections with antibiotics remains a riddle. The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of an antimicrobial agent provide important information helping to establish an efficient dosing regimen and to minimize the development of antimicrobial tolerance and resistance in biofilm infections. Unfortunately, most previous PK/PD studies of antibiotics have been done on planktonic cells, and extrapolation of the results on biofilms is problematic as bacterial biofilms differ from planktonic grown cells in the growth rate, gene expression, and metabolism. Here, we set up several protocols for the studies of PK/PD of antibiotics in biofilm infections of P. aeruginosa in vitro and in vivo. It should be underlined that none of the protocols in biofilms have yet been certificated for clinical use or proved useful for guidance of antibiotic therapy.

Key words

Biofilm Antibiotics PK/PD Pseudomonas aeruginosa 

References

  1. 1.
    Moskowitz SM, Emerson JC, McNamara S et al (2011) Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection. Pediatr Pulmonol 46:184–192PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Mueller M, de la Pena A, Derendorf H (2004) Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: kill curves versus MIC. Antimicrob Agents Chemother 48:369–377PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Høiby N, Krogh Johansen H, Moser C et al (2001) Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth. Microbes Infect 3:23–35PubMedCrossRefGoogle Scholar
  4. 4.
    Werner E, Roe F, Bugnicourt A et al (2004) Stratified growth in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 70:6188–6196PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Ceri H, Olson ME, Stremick C et al (1999) The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol 37:1771–1776PubMedCentralPubMedGoogle Scholar
  6. 6.
    Moskowitz SM, Foster JM, Emerson J, Burns JL (2004) Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol 42:1915–1922PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Nielsen EI, Viberg A, Lowdin E et al (2007) Semimechanistic pharmacokinetic/pharmacodynamic model for assessment of activity of antibacterial agents from time-kill curve experiments. Antimicrob Agents Chemother 51: 128–136PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Pankuch GA, Jacobs MR, Appelbaum PC (1994) Study of comparative antipneumococcal activities of penicillin-G, Rp-59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodology. Antimicrob Agents Chemother 38:2065–2072PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Hengzhuang W, Wu H, Ciofu O et al (2012) In vivo pharmacokinetics/pharmacodynamics of Colistin and Imipenem on biofilm Pseudomonas aeruginosa. Antimicrob Agents Chemother 56: 2683–2690PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Hengzhuang W, Ciofu O, Yang L et al (2013) High β-Lactamase levels change the pharmacodynamics of β-lactam antibiotics in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 57:196–204PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Hengzhuang W, Wu H, Ciofu O et al (2011) Pharmacokinetics/pharmacodynamics of Colistin and Imipenem on mucoid and nonmucoid Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 55:4469–4474PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    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 51:3677–3687PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Pedersen SS, Shand GH, Hansen BL, Hansen GN (1990) Induction of experimental chronic Pseudomonas aeruginosa lung infection with Pseudomonas aeruginosa entrapped in alginate microspheres. APMIS 98:203–211PubMedCrossRefGoogle Scholar
  14. 14.
    Wu H, Song ZJ, Hentzer M et al (2000) Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa. Microbiology 146: 2481–2493PubMedGoogle Scholar
  15. 15.
    Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York, NY, pp 451–457Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Clinical MicrobiologyRigshospitalet, University Hospital of CopenhagenCopenhagenDenmark

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