Skip to main content

Advertisement

SpringerLink
Log in

Clinical and microbiological profile of chronic Burkholderia cepacia complex infections in a cystic fibrosis reference hospital in Brazil

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Burkholderia sp. infections are extremely complex in cystic fibrosis (CF) patients, especially considering the lack of knowledge regarding its behavior, its relationship with prognosis, as well as its transmissibility and multidrug resistance features. This study evaluated the frequency of chronic infection by Burkholderia, using microbiological and clinical data. Ninety-eight patients with CF attended from July 2011 to April 2014 in a Brazilian reference hospital were included. Antimicrobial activity, molecular epidemiology, Shwachman score, body mass index, exacerbations, and lung function were analyzed. Nine patients had chronic colonization, and all of them showed preserved pulmonary function levels, body mass index, and Shwachman score. Meropenem was the most effective antibiotic; however, divergent results were shown by other studies. Cross-contamination may have occurred in only two unrelated patients of different ages, who were colonized by B. vietnamiensis, which does not occur frequently. Twelve new sequence types (STs) were identified and three STs have presented intercontinental distribution. None of the patients presented known epidemic strains. In conclusion, a relatively low number of patients with chronic colonization and suspected cross-infection were identified. Different from other studies that have found CF patients chronically colonized with Burkholderia sp. having a greater deterioration of lung function, more frequent antibiotic therapy, and increased mortality, in the current study, the patients showed good clinical outcomes and favorable options for antibiotics therapy. This study also updated the epidemiological database, which facilitates the multicentric collaborative analysis and assists in the control of global infection by these pathogens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hauser AR, Jain M, Bar-Meir M, McColley SA (2011) Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev 24:29–70. doi:10.1128/CMR.00036-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zemanick ET, Harris JK, Wagner BD, Robertson CE, Sagel SD, Stevens MJ et al (2013) Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS One 8:e62917. doi:10.1371/journal.pone.0062917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chmiel JF, Konstan MW, Elborn JS (2013) Antibiotic and anti-inflammatory therapies for cystic fibrosis. Cold Spring Harb Perspect Med 3:a009779. doi:10.1101/cshperspect.a009779

    Article  PubMed  PubMed Central  Google Scholar 

  4. De Smet B, Mayo M, Peeters C, Zlosnik JE, Spilker T, Hird TJ et al (2015) Burkholderia stagnalis sp. nov. and Burkholderia territorii sp. nov., two novel Burkholderia cepacia complex species from environmental and human sources. Int J Syst Evol Microbiol 65:2265–2271. doi:10.1099/ijs.0.000251

    Article  PubMed  Google Scholar 

  5. Lupo A, Isis E, Tinguely R, Endimiani A (2015) Clonality and antimicrobial susceptibility of Burkholderia cepacia complex isolates collected from cystic fibrosis patients during 1998–2013 in Bern, Switzerland. New Microbiol 38:281–288

    CAS  PubMed  Google Scholar 

  6. Caballero JdeD, del Campo R, Tato M, Gómez G de la Pedrosa E, Cobo M, López-Causapé C et al (2014) Microbiological diagnostic procedures for respiratory cystic fibrosis samples in Spain: towards standard of care practices. BMC Microbiol 14:335. doi: 10.1186/s12866-014-0335-y

  7. Schaffer K (2015) Epidemiology of infection and current guidelines for infection prevention in cystic fibrosis patients. J Hosp Infect 89:309–313. doi:10.1016/j.jhin.2015.02.005

    Article  CAS  PubMed  Google Scholar 

  8. Vasiljevic ZV, Novovic K, Kojic M, Minic P, Sovtic A, Djukic S et al (2016) Burkholderia cepacia complex in Serbian patients with cystic fibrosis: prevalence and molecular epidemiology. Eur J Clin Microbiol Infect Dis 35:1277–1284. doi:10.1007/s10096-016-2662-4

    Article  CAS  PubMed  Google Scholar 

  9. Spilker T, Baldwin A, Bumford A, Dowson CG, Mahenthiralingam E, LiPuma JJ (2009) Expanded multilocus sequence typing for Burkholderia species. J Clin Microbiol 47:2607–2610. doi:10.1128/JCM.00770-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Peeters C, Zlosnik JE, Spilker T, Hird TJ, LiPuma JJ, Vandamme P (2013) Burkholderia pseudomultivorans sp. nov., a novel Burkholderia cepacia complex species from human respiratory samples and the rhizosphere. Syst Appl Microbiol 36:483–489. doi:10.1016/j.syapm.2013.06.003

    Article  PubMed  Google Scholar 

  11. Barrado L, Martinez MT, Villa J, Orellana MÁ, Viedma E, Chaves F (2013) Clonal diversity among Burkholderia cepacia complex isolates from cystic fibrosis patients in a reference unit. Enferm Infecc Microbiol Clin 31:665–668. doi:10.1016/j.eimc.2013.04.025

    Article  PubMed  Google Scholar 

  12. Shwachman H, Kulczycki LL (1958) Long-term study of one hundred five patients with cystic fibrosis; studies made over a five- to fourteen-year period. AMA J Dis Child 96:6–15

    Article  CAS  PubMed  Google Scholar 

  13. Bilton D, Canny G, Conway S, Dumcius S, Hjelte L, Proesmans M et al (2011) Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF working group on outcome parameters in clinical trials. J Cyst Fibros 10:S79–S81. doi:10.1016/S1569-1993(11)60012-X

    Article  PubMed  Google Scholar 

  14. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A et al (2005) Standardisation of spirometry. Eur Respir J 26:319–338. doi: 10.1183/09031936.05.00034805

    Article  CAS  PubMed  Google Scholar 

  15. Sherrill DL, Lebowitz MD, Knudson RJ, Burrows B (1992) Continuous longitudinal regression equations for pulmonary function measures. Eur Respir J 5:452–462

    CAS  PubMed  Google Scholar 

  16. Gilligan PH, Kiska DL, Appleman MD (2006) Cumitech 43, cystic fibrosis microbiology. ASM Press, Washington, DC

    Google Scholar 

  17. Mahenthiralingam E, Bischof J, Byrne SK, Radomski C, Davies JE, Av-Gay Y et al (2000) DNA-based diagnostic approaches for identification of Burkholderia cepacia complex, Burkholderia vietnamiensis, Burkholderia multivorans, Burkholderia stabilis, and Burkholderia cepacia genomovars I and III. J Clin Microbiol 38:3165–3173

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Clinical and Laboratory Standards Institute (CLSI) (2016) Performance standards for antimicrobial susceptibility testing. CLSI document M100S, 26th edn. CLSI, Wayne, PA

  19. 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 35:2977–2980

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Medina-Pascual MJ, Valdezate S, Villalón P, Garrido N, Rubio V, Saéz-Nieto JA (2012) Identification, molecular characterisation and antimicrobial susceptibility of genomovars of the Burkholderia cepacia complex in Spain. Eur J Clin Microbiol Infect Dis 31:3385–3396. doi:10.1007/s10096-012-1707-6

    Article  CAS  PubMed  Google Scholar 

  21. Lambiase A, Del Pezzo M, Cerbone D, Raia V, Rossano F, Catania MR (2013) Rapid identification of Burkholderia cepacia complex species recovered from cystic fibrosis patients using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J Microbiol Methods 92:145–149. doi:10.1016/j.mimet.2012.11.010

    Article  CAS  PubMed  Google Scholar 

  22. AbdulWahab A, Taj-Aldeen SJ, Ibrahim EB, Talaq E, Abu-Madi M, Fotedar R (2015) Discrepancy in MALDI-TOF MS identification of uncommon Gram-negative bacteria from lower respiratory secretions in patients with cystic fibrosis. Infect Drug Resist 8:83–88. doi:10.2147/IDR.S80341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Alby K, Gilligan PH, Miller MB (2013) Comparison of matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry platforms for the identification of gram-negative rods from patients with cystic fibrosis. J Clin Microbiol 51:3852–3854. doi:10.1128/JCM.01618-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Boussaud V, Guillemain R, Grenet D, Coley N, Souilamas R, Bonnette P et al (2008) Clinical outcome following lung transplantation in patients with cystic fibrosis colonised with Burkholderia cepacia complex: results from two French centres. Thorax 63:732–737. doi:10.1136/thx.2007.089458

    Article  CAS  PubMed  Google Scholar 

  25. Coburn B, Wang PW, Diaz Caballero J, Clark ST, Brahma V, Donaldson S et al (2015) Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 5:10241. doi:10.1038/srep10241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vicenzi FJ, Pillonetto M, de Souza HAPHM, Palmeiro JK, Riedi CA, Rosario-Filho NA et al (2016) Polyphasic characterisation of Burkholderia cepacia complex species isolated from children with cystic fibrosis. Mem Inst Oswaldo Cruz 111:37–42. doi:10.1590/0074-02760150314

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fothergill JL, Walshaw MJ, Winstanley C (2012) Transmissible strains of Pseudomonas aeruginosa in cystic fibrosis lung infections. Eur Respir J 40:227–238. doi:10.1183/09031936.00204411

    Article  PubMed  Google Scholar 

  28. Fehlberg LCC, Nicoletti AG, Ramos AC, Rodrigues-Costa F, de Matos AP, Girardello R et al (2016) In vitro susceptibility of Burkholderia cepacia complex isolates: comparison of disk diffusion, Etest®, agar dilution, and broth microdilution methods. Diagn Microbiol Infect Dis 86:422–427. doi:10.1016/j.diagmicrobio.2016.08.015

    Article  CAS  PubMed  Google Scholar 

  29. Raidt L, Idelevich EA, Dübbers A, Küster P, Drevinek P, Peters G et al (2015) Increased prevalence and resistance of important pathogens recovered from respiratory specimens of cystic fibrosis patients during a decade. Pediatr Infect Dis J 34:700–705. doi:10.1097/INF.0000000000000714

    Article  PubMed  Google Scholar 

  30. Rhodes KA, Schweizer HP (2016) Antibiotic resistance in Burkholderia species. Drug Resist Updat 28:82–90. doi:10.1016/j.drup.2016.07.003

    Article  PubMed  PubMed Central  Google Scholar 

  31. Correa-Ruiz A, Girón R, Buendía B, Medina-Pascual MJ, Valenzuela C, López-Brea M et al (2013) Burkholderia cepacia complex infection in an adult cystic fibrosis unit in Madrid. Enferm Infecc Microbiol Clin 31:649–654. doi:10.1016/j.eimc.2012.12.001

    Article  PubMed  Google Scholar 

  32. Waine DJ, Whitehouse J, Honeybourne D (2007) Cross-infection in cystic fibrosis: the knowledge and behaviour of adult patients. J Cyst Fibros 6:262–266. doi:10.1016/j.jcf.2006.10.006

    Article  PubMed  Google Scholar 

  33. Wiener-Well Y, Segonds C, Mazuz B, Kopuit P, Assous MV (2014) Successful outbreak investigation of Burkholderia cepacia complex bacteremia in intensive care patients. Am J Infect Control 42:580–581. doi:10.1016/j.ajic.2013.12.015

    Article  PubMed  Google Scholar 

  34. Dedeckova K, Fila L, Skalicka V, Bartosova J, Kucerova T, Vavrova V et al (2012) PCR detection of Burkholderia cepacia complex as one of key factors to handle a long-term outbreak. J Cyst Fibros 11:440–445. doi:10.1016/j.jcf.2012.04.005

    Article  CAS  PubMed  Google Scholar 

  35. Nannini EC, Ponessa A, Muratori R, Marchiaro P, Ballerini V, Flynn L et al (2015) Polyclonal outbreak of bacteremia caused by Burkholderia cepacia complex and the presumptive role of ultrasound gel. Braz J Infect Dis 19:543–545. doi:10.1016/j.bjid.2015.06.009

    Article  PubMed  Google Scholar 

  36. Shommu NS, Vogel HJ, Storey DG (2015) Potential of metabolomics to reveal Burkholderia cepacia complex pathogenesis and antibiotic resistance. Front Microbiol 6:668. doi:10.3389/fmicb.2015.00668

    Article  PubMed  PubMed Central  Google Scholar 

  37. Coutinho CP, Dos Santos SC, Madeira A, Mira NP, Moreira AS, Sá-Correia I (2011) Long-term colonization of the cystic fibrosis lung by Burkholderia cepacia complex bacteria: epidemiology, clonal variation, and genome-wide expression alterations. Front Cell Infect Microbiol 1:12. doi:10.3389/fcimb.2011.00012

    Article  PubMed  PubMed Central  Google Scholar 

  38. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH et al (1995) Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33:2233–2239

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Fernández-Olmos A, García-Castillo M, Alba JM, Morosini MI, Lamas A, Romero B et al (2013) Population structure and antimicrobial susceptibility of both nonpersistent and persistent Pseudomonas aeruginosa isolates recovered from cystic fibrosis patients. J Clin Microbiol 51:2761–2765. doi:10.1128/JCM.00802-13

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gautam V, Patil PP, Kumar S, Midha S, Kaur M, Kaur S et al (2016) Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India. Sci Rep 6:35769. doi:10.1038/srep35769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We wish to thank Lucélia A. Pereira for the Vitek® 2 identification of isolates and Joseane C. Ferreira and Rubens E. Silva for their technical assistance. We would like to thank Roberto Martinez from Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto for the clinical isolates provided. We acknowledge Elizabeth Andrade Marques from Universidade Estadual do Rio de Janeiro and Carlos Emílio Levy from Universidade Estadual de Campinas, who kindly provided standard strains used as controls.

Author information

Authors and Affiliations

  1. Department of Clinical Analysis, Toxicological and Bromatological, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

    C. P. da Costa Capizzani, N. C. Caçador, L. Tonani & A. L. da Costa Darini

  2. Department of Pediatrics, Cystic Fibrosis Referral Service, Clinic Hospital of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    L. A. G. M. M. Torres

  3. Laboratory of Microbiology, Ghent University, Ghent, Belgium

    P. Vandamme

  4. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

    A. L. da Costa Darini

Authors
  1. C. P. da Costa Capizzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. C. Caçador
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. A. G. M. M. Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Tonani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Vandamme
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. L. da Costa Darini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. L. da Costa Darini.

Ethics declarations

Funding

This study was funded by the São Paulo Research Foundation (FAPESP, grant number 2014/14494-8). CPCC and NCC were supported by PhD fellowships from the FAPESP (grant numbers 2013/13455-6 and 2013/13358-0).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Research Ethics Committee of Faculdade de Ciências Farmacêuticas de Ribeirão Preto of the University of Sao Paulo by the number 210, with the agreement of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, University of São Paulo (HCFMRP-USP).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Costa Capizzani, C.P., Caçador, N.C., Torres, L.A.G.M.M. et al. Clinical and microbiological profile of chronic Burkholderia cepacia complex infections in a cystic fibrosis reference hospital in Brazil. Eur J Clin Microbiol Infect Dis 36, 2263–2271 (2017). https://doi.org/10.1007/s10096-017-3058-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-017-3058-9

Keywords

Search

Navigation