Advertisement

Variation of the antimicrobial susceptibility profiles of Burkholderia cepacia complex clonal isolates obtained from chronically infected cystic fibrosis patients: a five-year survey in the major Portuguese treatment center

  • J. H. Leitão
  • S. A. Sousa
  • M. V. Cunha
  • M. J. Salgado
  • J. Melo-Cristino
  • M. C. Barreto
  • I. Sá-CorreiaEmail author
Article

Abstract

The treatment of cystic fibrosis (CF) patients chronically infected with Burkholderia cepacia complex (Bcc) bacteria requires extensive and aggressive antibiotics therapy, exposing these bacteria to prolonged antibiotics-selective pressure. In the present study, we have compared the susceptibility patterns to 13 antimicrobials of 94 Bcc isolates obtained from 15 Portuguese CF patients in the course of chronic infection during a five-year survey. These isolates were previously genotyped and represent 11 different strains of the species B. cenocepacia (subgroups A and B), B. cepacia, B. multivorans, and B. stabilis. The results are consistent with the notion that CF Bcc isolates are resistant to the most clinically relevant antimicrobials and suggest an uneven distribution of resistance rates among the different species, with B. cenocepacia subgroup A isolates being the most resistant. Phenotypic variants exhibiting differences in the antimicrobial susceptibility patterns were obtained from the sputum samples of clinically deteriorated CF patients during chronic lung infection. The isolation of resistant variants coincided with periods of pulmonary exacerbation and antibiotics therapy.

Keywords

Cystic Fibrosis Minimal Inhibitory Concentration Ceftazidime Cystic Fibrosis Patient Antimicrobial Susceptibility Pattern 
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.

Abbreviations

Bcc

Burkholderia cepacia complex

IV

Intravenous therapy

IT

Inhaled tobramycin

Notes

Acknowledgments

This work was partially supported by FEDER and Fundação para a Ciência e Tecnologia (FCT), Portugal (contracts POCTI/BIO/38273/2001 and PTDC/SAU-MII/69591/2006 and PhD and post-doctoral grants to S.A.S and M.V.C., respectively).

References

  1. 1.
    Mahenthiralingam E, Urban TA, Goldberg JB (2005) The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3:144–156PubMedCrossRefGoogle Scholar
  2. 2.
    LiPuma JJ (2003) Burkholderia and emerging pathogens in cystic fibrosis. Semin Respir Crit Care Med 24:681–692PubMedCrossRefGoogle Scholar
  3. 3.
    Speert DP (2002) Advances in Burkholderia cepacia complex. Paediatr Respir Rev 3:230–235PubMedCrossRefGoogle Scholar
  4. 4.
    Collins FS (1992) Cystic fibrosis: molecular biology and therapeutic implications. Science 256:774–779PubMedCrossRefGoogle Scholar
  5. 5.
    Cunha MV, Leitão JH, Mahenthiralingam E, Vandamme P, Lito L, Barreto C, Salgado MJ, Sá-Correia I (2003) Molecular analysis of Burkholderia cepacia complex isolates from a Portuguese cystic fibrosis center: a 7-year study. J Clin Microbiol 41:4113–4120PubMedCrossRefGoogle Scholar
  6. 6.
    Cunha MV, Pinto-de-Oliveira A, Meirinhos-Soares L, Melo-Cristino J, Salgado MJ, Correia S, Barreto C, Sá-Correia I (2007) Exceptionally high representation of Burkholderia cepacia among B. cepacia complex isolates recovered from the major Portuguese cystic fibrosis center. J Clin Microbiol 45:1628–1633PubMedCrossRefGoogle Scholar
  7. 7.
    Agodi A, Mahenthiralingam E, Barchitta M, Gianninò V, Sciacca A, Stefani S (2001) Burkholderia cepacia complex infection in Italian patients with cystic fibrosis: prevalence, epidemiology, and genomovar status. J Clin Microbiol 39:2891–2896PubMedCrossRefGoogle Scholar
  8. 8.
    Brisse S, Cordevant C, Vandamme P, Bidet P, Loukil C, Chabanon G, Lange M, Bingen E (2004) Species distribution and ribotype diversity of Burkholderia cepacia complex isolates from French patients with cystic fibrosis. J Clin Microbiol 42:4824–4827PubMedCrossRefGoogle Scholar
  9. 9.
    Campana S, Taccetti G, Ravenni N, Favari F, Cariani L, Sciacca A, Savoia D, Collura A, Fiscarelli E, De Intinis G, Busetti M, Cipolloni A, d’Aprile A, Provenzano E, Collebrusco I, Frontini P, Stassi G, Trancassini M, Tovagliari D, Lavitola A, Doherty CJ, Coenye T, Govan JRW, Vandamme P (2005) Transmission of Burkholderia cepacia complex: evidence for new epidemic clones infecting cystic fibrosis patients in Italy. J Clin Microbiol 43:5136–5142PubMedCrossRefGoogle Scholar
  10. 10.
    LiPuma JJ, Spilker T, Gill LH, Campbell PW 3rd, Liu L, Mahenthiralingam E (2001) Disproportionate distribution of Burkholderia cepacia complex species and transmissibility markers in cystic fibrosis. Am J Respir Crit Care Med 164:92–96PubMedGoogle Scholar
  11. 11.
    Reik R, Spilker T, LiPuma JJ (2005) Distribution of Burkholderia cepacia complex species among isolates recovered from persons with or without cystic fibrosis. J Clin Microbiol 43:2926–2928PubMedCrossRefGoogle Scholar
  12. 12.
    Speert DP, Henry D, Vandamme P, Corey M, Mahenthiralingam E (2002) Epidemiology of Burkholderia cepacia complex in patients with cystic fibrosis, Canada. Emerg Infect Dis 8:181–187PubMedGoogle Scholar
  13. 13.
    Isles A, Maclusky I, Corey M, Gold R, Prober C, Fleming P, Levison H (1984) Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr 104:206–210PubMedCrossRefGoogle Scholar
  14. 14.
    Furukawa S, Kuchma SL, O’Toole GA (2006) Keeping their options open: acute versus persistent infections. J Bacteriol 188:1211–1217PubMedCrossRefGoogle Scholar
  15. 15.
    Fux CA, Costerton JW, Stewart PS, Stoodley P (2005) Survival strategies of infectious biofilms. Trends Microbiol 13:34–40PubMedCrossRefGoogle Scholar
  16. 16.
    Bevivino A, Dalmastri C, Tabacchioni S, Chiarini L, Belli ML, Piana S, Materazzo A, Vandamme P, Manno G (2002) Burkholderia cepacia complex bacteria from clinical and environmental sources in Italy: genomovar status and distribution of traits related to virulence and transmissibility. J Clin Microbiol 40:846–851PubMedCrossRefGoogle Scholar
  17. 17.
    Bauer AN, Kirby WMM, Sherris JC, Turck M (1966) Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 45:493–496PubMedGoogle Scholar
  18. 18.
    Clinical Laboratory Standards Institute (CLSI) (2005) Performance standards for antimicrobial susceptibility testing; fifteenth informational supplement. National Committee for Clinical Laboratory Standards (NCCLS), M100-S15 (vol. 25, no.1)Google Scholar
  19. 19.
    Mackenzie FM, Smith SV, Milne KE, Griffiths K, Legge J, Gould IM (2004) Antibiograms of resistant Gram-negative bacteria from Scottish CF patients. J Cystic Fibrosis 3:151–157CrossRefGoogle Scholar
  20. 20.
    Pitt TL, Kaufmann ME, Patel PS, Benge LCA, Gaskin S, Livermore DM (1996) Type characterisation and antibiotic susceptibility of Burkholderia (Pseudomonas) cepacia isolates from patients with cystic fibrosis in the United Kingdom and the Republic of Ireland. J Med Microbiol 44:203–210PubMedCrossRefGoogle Scholar
  21. 21.
    Sader HS, Jones RN (2005) Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli. Int J Antimicrob Agents 25:95–109PubMedCrossRefGoogle Scholar
  22. 22.
    Zhou J, Chen Y, Tabibi S, Alba L, Garber E, Saiman L (2007) Antimicrobial susceptibility and synergy studies of Burkholderia cepacia complex isolated from patients with cystic fibrosis. Antimicrob Agents Chemother 51:1085–1088PubMedCrossRefGoogle Scholar
  23. 23.
    Gold R, Jin E, Levison H, Isles A, Fleming PC (1983) Ceftazidime alone and in combination in patients with cystic fibrosis: lack of efficacy in treatment of severe respiratory infections caused by Pseudomonas cepacia. J Antimicrob Chemother 12(Suppl A):331–336PubMedGoogle Scholar
  24. 24.
    Golini G, Cazzola G, Fontana R (2006) Molecular epidemiology and antibiotic susceptibility of Burkholderia cepacia-complex isolates from an Italian cystic fibrosis centre. Eur J Clin Microbiol Infect Dis 25:175–180PubMedCrossRefGoogle Scholar
  25. 25.
    Nzula S, Vandamme P, Govan JRW (2002) Influence of taxonomic status on the in vitro antimicrobial susceptibility of the Burkholderia cepacia complex. J Antimicrob Chemother 50:265–269PubMedCrossRefGoogle Scholar
  26. 26.
    Caraher E, Reynolds G, Murphy P, McClean S, Callaghan M (2007) Comparison of antibiotic susceptibility of Burkholderia cepacia complex organisms when grown planktonically or as biofilm in vitro. Eur J Clin Microbiol Infect Dis 26:213–216PubMedCrossRefGoogle Scholar
  27. 27.
    Cunha MV, Sousa SA, Leitão JH, Moreira LM, Videira PA, Sá-Correia I (2004) Studies on the involvement of the exopolysaccharide produced by cystic fibrosis-associated isolates of the Burkholderia cepacia complex in biofilm formation and in persistence of respiratory infections. J Clin Microbiol 42:3052–3058PubMedCrossRefGoogle Scholar
  28. 28.
    St Denis MS, Ramotar K, Vandemheen K, Tullis E, Ferris W, Chan F, Lee C, Slinger R, Aaron SD (2007) Infection with Burkholderia cepacia complex bacteria and pulmonary exacerbations of cystic fibrosis. Chest 131:1188–1196PubMedCrossRefGoogle Scholar
  29. 29.
    Denamur E, Matic I (2006) Evolution of mutation rates in bacteria. Mol Microbiol 60:820–827PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • J. H. Leitão
    • 1
  • S. A. Sousa
    • 1
  • M. V. Cunha
    • 1
  • M. J. Salgado
    • 2
  • J. Melo-Cristino
    • 2
  • M. C. Barreto
    • 3
  • I. Sá-Correia
    • 1
    Email author
  1. 1.IBB—Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical EngineeringInstituto Superior TécnicoLisboaPortugal
  2. 2.Laboratório de BacteriologiaHospital de Santa MariaLisboaPortugal
  3. 3.Centro Especializado em Fibrose QuísticaHospital de Santa MariaLisboaPortugal

Personalised recommendations