Skip to main content

Advertisement

SpringerLink
Log in

The efficacy of fidaxomicin in the treatment of Clostridium difficile infection in a real-world clinical setting: a Spanish multi-centre retrospective cohort

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

Abstract

The objective of this study was to evaluate the efficacy and safety of fidaxomicin in the real-life clinical setting. This was a retrospective cohort of patients with Clostridium difficile infection (CDI) treated with fidaxomicin in 20 Spanish hospitals between July 2013 and July 2014. Clinical cure, 30-day recurrence, 30-day mortality, sustained cure, and factors associated with the failure to achieve sustained cure were analyzed. Of the 72 patients in the cohort 41 (56.9 %) had a fatal underlying disease. There were 44 (61.1 %) recurrent episodes and 26 cases (36.1 %) with a history of multiple recurrences. Most episodes were severe (26, 36 %) or severe-complicated (14, 19.4 %). Clinical cure rate was 90.3 %, recurrence rate was 16.7 % and three patients (4.2 %) died during the follow-up period. Sustained cure was achieved in 52 cases (72.2 %). Adverse events were reported in five cases (6.9 %). Factors associated with the lack of sustained cure were cardiovascular comorbidity (OR 11.4; 95 %CI 1.9–67.8), acute kidney failure (OR 7.4; 95 %CI 1.3–43.1), concomitant systemic antibiotic treatment (OR 6.2; 95 %CI 1.1–36.8), and C-reactive protein value at diagnosis (OR 1.2 for each 1 mg/dl increase; 95 %CI 1.03–1.3). Fidaxomicin is an effective and well tolerable treatment for severe CDI and for cases with elevated recurrence risk.

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

Similar content being viewed by others

References

  1. Debast SB, Bauer MP, Kuijper EJ (2014) European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 20(Suppl 2):1–26. doi:10.1111/1469-0691.12418

    Article  CAS  PubMed  Google Scholar 

  2. Cornely O, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K et al (2012) Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet 12:281–289. doi:10.1016/S0140-6736(11)61514-6.WEB-ONLY

    Article  CAS  PubMed  Google Scholar 

  3. Louie TJ, Miller MA, Mullane K, Weiss K, Lentnek A, Golan Y et al (2011) Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 364:422–431

    Article  CAS  PubMed  Google Scholar 

  4. Cornely OA, Nathwani D, Ivanescu C, Odufowora-Sita O, Retsa P, Odeyemi IAO (2014) Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison. J Antimicrob Chemother 69:2892–2900. doi:10.1093/jac/dku261

    Article  CAS  PubMed  Google Scholar 

  5. Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL (2012) Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis 55(Suppl 2):S154–S161. doi:10.1093/cid/cis462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Goldstein EJC, Babakhani F, Citron DM (2012) Antimicrobial activities of fidaxomicin. Clin Infect Dis 55:143–148. doi:10.1093/cid/cis339

    Article  Google Scholar 

  7. Louie TJ, Cannon K, Byrne B, Emery J, Ward L, Eyben M et al (2012) Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile Infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis 55:S132–S142. doi:10.1093/cid/cis338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Babakhani F, Bouillaut L, Gomez A, Sears P, Nguyen L, Sonenshein AL (2012) Fidaxomicin inhibits spore production in clostridium difficile. Clin Infect Dis 55:S162–S169. doi:10.1093/cid/cis453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Biswas JS, Patel A, Otter JA, Wade P, Newsholme W, van Kleef E et al (2015) Reduction in Clostridium difficile environmental contamination by hospitalized patients treated with fidaxomicin. J Hosp Infect 90:267–270. doi:10.1016/j.jhin.2015.01.015

    Article  CAS  PubMed  Google Scholar 

  10. Oshima H, Yamazaki T, Benner L, Miki T, Michon I, Wojtkowski T et al (2015) Comparison of the safety, tolerability, and pharmacokinetics of fidaxomicin in healthy Japanese and Caucasian subjects. Clin Drug Investig 35:375–384. doi:10.1007/s40261-015-0291-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Deshpande A, Hurless K, Cadnum JL, Chesnel L, Gao L, Chan L et al (2016) Effect of fidaxomicin versus vancomycin on susceptibility to intestinal colonization with vancomycin-resistant enterococci and Klebsiella pneumoniae in mice. Antimicrob Agents Chemother 60:3988–3993. doi:10.1128/AAC.02904-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Snydman DR, McDermott LA, Jacobus NV, Thorpe C, Stone S, Jenkins SG et al (2015) U.S.-based national sentinel surveillance study for the epidemiology of clostridium difficile-associated diarrheal isolates and their susceptibility to fidaxomicin. Antimicrob Agents Chemother 59:6437–6443. doi:10.1128/AAC.00845-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Freeman J, Vernon J, Morris K, Nicholson S, Todhunter S, Longshaw C et al (2015) Pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes. Clin Microbiol Infect 21:248.e9–248.e16. doi:10.1016/j.cmi.2014.09.017

    Article  CAS  Google Scholar 

  14. Leeds JA, Sachdeva M, Mullin S, Barnes SW, Ruzin A (2014) In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin. J Antimicrob Chemother 69:41–44. doi:10.1093/jac/dkt302

    Article  CAS  PubMed  Google Scholar 

  15. Babakhani F, Gomez A, Robert N, Sears P (2011) Postantibiotic effect of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile. Antimicrob Agents Chemother 55:4427–4429. doi:10.1128/AAC.00104-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jin J, Sklar GE, Oh VMS, Li SC (2008) Factors affecting therapeutic compliance: a review from the patient’s perspective. Ther Clin Risk Manag 4:269–286

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sartelli M, Malangoni MA, Abu-Zidan FM, Griffiths EA, Di Bella S, McFarland LV et al (2015) WSES guidelines for management of Clostridium difficile infection in surgical patients. World J Emerg Surg 10:38. doi:10.1186/s13017-015-0033-6

    Article  PubMed  PubMed Central  Google Scholar 

  18. Trubiano JA, Cheng AC, Korman TM, Roder C, Campbell A, May MLA et al (2016) Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand. Intern Med J 46:479–493. doi:10.1111/imj.13027

    Article  CAS  PubMed  Google Scholar 

  19. Eiland EH, Sawyer AJ, Massie NL (2015) Fidaxomicin use and clinical outcomes for clostridium difficile-associated diarrhea. Infect Dis Clin Pract 23:32–35. doi:10.1097/IPC.0000000000000181

    Article  Google Scholar 

  20. Vargo CA, Bauer KA, Mangino JE, Johnston JEW, Goff DA (2014) An antimicrobial stewardship program’s real-world experience with fidaxomicin for treatment of clostridium difficile infection: a case series. Pharmacotherapy 34:901–909. doi:10.1002/phar.1451

    Article  CAS  PubMed  Google Scholar 

  21. Esmaily-Fard A, Tverdek FP, Crowther DM, Ghantoji SS, Adachi JA, Chemaly RF (2014) The use of fidaxomicin for treatment of relapsed clostridium difficile infections in patients with cancer. Pharmacotherapy 34:1220–1225. doi:10.1002/phar.1479

    Article  CAS  PubMed  Google Scholar 

  22. Penziner S, Dubrovskaya Y, Press R, Safdar A (2015) Fidaxomicin therapy in critically ill patients with clostridium difficile infection. Antimicrob Agents Chemother 59:1776–1781. doi:10.1128/AAC.04268-14

    Article  PubMed  PubMed Central  Google Scholar 

  23. Clutter DS, Dubrovskaya Y, Merl MY, Teperman L, Press R, Safdar A (2013) Fidaxomicin versus conventional antimicrobial therapy in 59 recipients of solid organ and hematopoietic stem cell transplantation with clostridium difficile-associated diarrhea. Antimicrob Agents Chemother 57:4501–4505. doi:10.1128/AAC.01120-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gallagher JC, Reilly JP, Navalkele B, Downham G, Haynes K, Trivedi M (2015) Clinical and economic benefits of fidaxomicin compared to vancomycin for clostridium difficile infection. Antimicrob Agents Chemother 59:7007–7010. doi:10.1128/AAC.00939-15.Address

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Goldenberg S, Brown S, Edwards L, Gnanarajah D, Howard P, Jenkins D et al (2016) The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations. Eur J Clin Microbiol Infect Dis 35:251–259. doi:10.1007/s10096-015-2538-z

    Article  CAS  PubMed  Google Scholar 

  26. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 31:1250–1256. doi:10.1097/01.CCM.0000050454.01978.3B

    Article  PubMed  Google Scholar 

  27. Charlson ME, Pompei P, Ales KL, MacKenzie R (1987) A new method of classifying prognostic in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383

  28. McCabe WR, Jackson GG (1962) Gram-negative bacteremia I. etiology and ecology. Arch Intern Med 110:847–855. doi:10.1001/archinte.1962.03620240029006

    Article  Google Scholar 

  29. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC et al (2010) Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 31:431–455. doi:10.1086/651706

    Article  PubMed  Google Scholar 

  30. Miller MA, Louie T, Mullane K, Weiss K, Lentnek A, Golan Y et al (2013) Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect Dis 13:148–154. doi:10.1186/1471-2334-13-148

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bauer MP, Hensgens MPM, Miller MA, Gerding DN, Wilcox MH, Dale AP et al (2012) Renal failure and leukocytosis are predictors of a complicated course of clostridium difficile infection if measured on day of diagnosis. Clin Infect Dis 55:149–153. doi:10.1093/cid/cis340

    Article  Google Scholar 

  32. Cadena J, Thompson GR, Patterson JE, Nakashima B, Owens A, Echevarria K et al (2010) Clinical predictors and risk factors for relapsing clostridium difficile infection. Am J Med Sci 339:350–355

    Article  PubMed  Google Scholar 

  33. Dudukgian H, Sie E, Gonzalez-Ruiz C, Etzioni DA, Kaiser AM (2010) C. difficile colitis-predictors of fatal outcome. J Gastrointest Surg 14:315–322. doi:10.1007/s11605-009-1093-2

    Article  PubMed  Google Scholar 

  34. Abou Chakra CN, Pepin J, Sirard S, Valiquette L (2014) Risk factors for recurrence, complications and mortality in clostridium difficile infection: a systematic review. PLoS One 9:e98400. doi:10.1371/journal.pone.0098400

    Article  PubMed  PubMed Central  Google Scholar 

  35. Garey KW, Sethi S, Yadav Y, Dupont HL (2008) Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect 70:298–304. doi:10.1016/j.jhin.2008.08.012

    Article  CAS  PubMed  Google Scholar 

  36. Crook DW, Walker AS, Kean Y, Weiss K, Cornely OA, Miller MA et al (2012) Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis 55(Suppl 2):S93–S103. doi:10.1093/cid/cis499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hu MY, Katchar K, Kyne L, Maroo S, Tummala S, Dreisbach V et al (2009) Prospective derivation and validation of a clinical prediction rule for recurrent clostridium difficile infection. Gastroenterology 136:1206–1214. doi:10.1053/j.gastro.2008.12.038

    Article  PubMed  Google Scholar 

  38. Eyre DW, Walker AS, Wyllie D, Dingle KE, Grif D, Finney J et al (2012) Predictors of first recurrence of clostridium difficile infection: implications for initial management. Clin Infect Dis 55:77–87. doi:10.1093/cid/cis356

    Article  Google Scholar 

  39. Hardt C, Berns T, Treder W, Dumoulin FL, Hardt C, Dumoulin FL (2008) Univariate and multivariate analysis of risk factors for severe clostridium difficile -associated diarrhoea: Importance of co-morbidity and serum C-reactive protein. World J Gastroenterol 14:4338–4341. doi:10.3748/wjg.14.4338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Miller M, Gravel D, Mulvey M, Taylor G, Boyd D, Simor A et al (2010) Health care – associated clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis 50:194–201. doi:10.1086/649213

    Article  PubMed  Google Scholar 

  41. Andrews CN, Raboud J, Frcpc BOK, Frcpc RE, Andrews CN, Raboud J et al (2003) Clostridium difficile-associated diarrhea: predictors of severity in patients presenting to the emergency department. Can J Gastroenterol 17:369–373

    Article  PubMed  Google Scholar 

  42. Wilson V, Cheek L, Satta G, Walker-bone K, Cubbon M, Citron D et al (2010) Predictors of death after clostridium difficile infection: a report on 128 strain-typed cases from a teaching hospital in the United Kingdom. Clin Infect Dis 50:e77–e81. doi:10.1086/653012

    Article  CAS  PubMed  Google Scholar 

  43. Cober ED, Malani PN (2009) Clostridium difficile infection in the “oldest” old: clinical outcomes in patients aged 80 and older. J Am Geriatr Soc 57:659–662. doi:10.1111/j.1532-5415.2009.02182.x

    Article  PubMed  Google Scholar 

  44. Welfare MR, Lalayiannis LC, Martin KE, Corbett S, Marshall B, Sarma JB (2011) Co-morbidities as predictors of mortality in Clostridium difficile infection and derivation of the ARC predictive score. J Hosp Infect 79:359–363. doi:10.1016/j.jhin.2011.08.015

    Article  CAS  PubMed  Google Scholar 

  45. McDonald EG, Milligan J, Frenette C, Lee TC (2015) Continuous proton pump inhibitor therapy and the associated risk of recurrent clostridium difficile infection. JAMA Intern Med 175:784–794. doi:10.1001/jamainternmed.2015.42

    Article  PubMed  Google Scholar 

  46. Deshpande A, Pasupuleti V, Thota P, Pant C, Rolston DDK, Hernandez AV et al (2015) Risk factors for recurrent clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 36:452–460. doi:10.1017/ice.2014.88

    Article  PubMed  Google Scholar 

  47. Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK (2012) Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol 107:1011–1019. doi:10.1038/ajg.2012.108

    Article  CAS  PubMed  Google Scholar 

  48. Rea MC, Dobson A, O’Sullivan O, Crispie F, Fouhy F, Cotter PD et al (2011) Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon. Proc Natl Acad Sci USA 108:4639–4644. doi:10.1073/pnas.1001224107

    Article  CAS  PubMed  Google Scholar 

  49. Lewis BB, Buffie CG, Carter RA, Leiner I, Toussaint NC, Miller LC et al (2015) Loss of microbiota-mediated colonization resistance to Clostridium difficile infection with oral vancomycin compared with metronidazole. J Infect Dis 212:1656–1665. doi:10.1093/infdis/jiv256

    Article  PubMed  PubMed Central  Google Scholar 

  50. Bassis CM, Theriot CM, Young VB (2014) Alteration of the murine gastrointestinal microbiota by tigecycline leads to increased susceptibility to clostridium difficile infection. Antimicrob Agents Chemother 58:2767–2774. doi:10.1128/AAC.02262-13

    Article  PubMed  PubMed Central  Google Scholar 

  51. Watt M, McCrea C, Johal S, Posnett J, Nazir J (2016) A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany. Infection 44(5):599–606. doi:10.1007/s15010-016-0894-y

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to express their gratitude for the data collection to the following people: María Soledad Azcona, Unit of Internal Medicine, Hospital Santa Marina, Bilbao, Spain. Cristina Badía, Unit of Nosocomial Infections, Hospital Universitari Mútua Terrassa, Terrassa (Barcelona), Spain. Juan Miguel Bergua Burgués, Department of Hematology Department. Hospital San Pedro de Alcántara, Cáceres, Spain. María Bodi, Department of Critical Surgical Care, Hospital Joan XXIII, Tarragona, Spain. María Teresa Bravo Fernández, Department of Gastroenterology, Hospital de Basurto, Bilbao, Spain. Elena Chamorro, Unit of Internal Medicine, Hospital Verge de la Cinta, Tortosa, Spain. Beatriz Díaz Pollán, Unit of Infectious Diseases and Clinical Microbiology, Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain. Elena Espejo, Unit of Infectious Diseases, Department of Internal Medicine, Consorci Sanitari de Terrassa, Terrassa, Spain. Alicia Hernández Torre, Department of Infectious Diseases, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. Samantha Elizabeth de Jesús, Department of Infectious Diseases, Hospital Universitario Virgen de las Nieves, Granada, Spain. Belén Loeches Yagüe, Unit of Infectious Diseases and Clinical Microbiology, Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain. Thais López, Department of Infectious Diseases, Hospital Vall d’Hebron, Barcelona, Spain. Helena Monzón. Unit of Internal Medicine, Hospital San Joan de Deu, Martorell, Spain. Juan Francisco Pascual Gázquez, Department of Paediatric Haematology and Oncology. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. Alicia Rico Nieto, Unit of Infectious Diseases and Clinical Microbiology, Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain. Andrés Sánchez Salinas, Department of Hematology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. Julio Valle, Department of Gastroenterology, Hospital Virgen de la Salud, Toledo, Spain.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Hospital Clínic de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain

    C. Fehér & J. Mensa

  2. Unit of Infectious Diseases, Department of Internal Medicine, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain

    E. Múñez Rubio

  3. Department of Microbiology, Hospital Clínico San Carlos, Madrid, Spain

    P. Merino Amador

  4. Department of Microbiology, Fundación Hospital Alcorcón, Madrid, Spain

    A. Delgado-Iribarren Garcia-Campero

  5. Unit of Infectious Diseases, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    M. Salavert

  6. Unit of Infectious Diseases, Hospital General Universitario de Alicante, Alicante, Spain

    E. Merino

  7. Department of Anesthesiology and Critical Surgical Care, Hospital Universitario La Paz, Madrid, Spain

    E. Maseda Garrido

  8. Unit of Infectious Diseases, Parc Sanitari Sant Joan de Deu, Sant Boi de Llobregat, Barcelona, Spain

    V. Díaz-Brito

  9. Department of Microbiology, Hospital Clínic de Barcelona, Barcelona, Spain

    M. J. Álvarez

Authors
  1. C. Fehér
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Múñez Rubio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Merino Amador
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Delgado-Iribarren Garcia-Campero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Salavert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Merino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. Maseda Garrido
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. V. Díaz-Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. J. Álvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. Mensa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Fehér.

Ethics declarations

Conflict of interest

C. F. received support to attend scientific meetings and congresses from Glaxo-Smith-Klein, Pfizer, Astellas and Gilead. E. M. R. received honoraria from Astellas for scientific presentations. M. S. gave scientific presentations at meetings organized by Pfizer, Astellas, MSD, Novartis and Gilead, and received grants for research projects and clinical trials from Astellas and MSD. V. D. B. received lecture fees, travel support for attending meetings and fees for advisory boards from Novartis, Astellas, Merck and Pfizer. J. M. gave scientific presentations at meetings organized by Novartis, Pfizer, MSD, Astellas, and Gilead. All other authors had no competing interests to declare.

Funding

This work was an Investigator Sponsored Research supported by Astellas Pharma.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fehér, C., Múñez Rubio, E., Merino Amador, P. et al. The efficacy of fidaxomicin in the treatment of Clostridium difficile infection in a real-world clinical setting: a Spanish multi-centre retrospective cohort. Eur J Clin Microbiol Infect Dis 36, 295–303 (2017). https://doi.org/10.1007/s10096-016-2802-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-016-2802-x

Keywords

Search

Navigation