Skip to main content

Advertisement

SpringerLink
Log in

Investigation of Clostridium difficile ribotypes in symptomatic patients of a German pediatric oncology center

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

In a German pediatric oncology unit, the attending physicians diagnosed 27 cases of Clostridium difficile-associated disease (CDI) from January 01, 2010 to October 31, 2013. This refers to a CDI incidence density of 2.0/1000 inpatient days. According to the hospital hygiene standard, symptomatic patients with CDI were kept in contact isolation. Most patients (median age 8.2 years) suffered from acute lymphoblastic leukemia; 88.9% were treated with broad-spectrum antibiotics during the preceding 4 weeks. 29.6% received intravenous morphine/metamizole and parenteral nutrition due to severe chemotherapy-induced mucositis. None of the patients experienced severe complications such as lower gastrointestinal tract bleeding, sepsis, or toxic megacolon. Genotyping of the isolates derived from symptomatic patients revealed many different ribotypes without detection of the hypervirulent 027 strain and did not point at hospital transmission as an important promoter of CDI in our unit.

Conclusion: Under strict standard hygiene and contact isolation for symptomatic patients, genotyping of clinical isolates revealed that in pediatric cancer patients, CDI is not necessarily based on nosocomial transmission. The rate of CDI-related severe complications was low.

What is Known:

• Pediatric cancer patients face an increased risk of Clostridium difficile-associated disease due to immunosuppression, cancer chemotherapy, mucositis, and dysbiosis following intravenous broad-spectrum antimicrobial treatment.

• C. difficile may be transmitted from patient to patient.

What is New:

• Under strict standard hygiene and contact isolation for symptomatic patients, genotyping of clinical isolates revealed that in pediatric cancer patients, CDI is not necessarily based on nosocomial transmission.

• The rate of CDI-related severe complications was low.

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
Fig. 3

Similar content being viewed by others

Abbreviations

ALL:

Acute lymphoblastic leukemia

CD:

Clostridium difficile

CDI:

Clostridium difficile-associated disease

EIA:

Enzyme immunoassay

GLDH:

Glutamate dehydrogenase

HA-CDI:

Healthcare-associated CDI

ID:

Incidence density

POC:

Pediatric oncology center

PPI:

Proton pump inhibitor

rCDI:

Recurrent CDI

References

  1. de Blank P, Zaoutis T, Fisher B, Troxel A, Kim J, Aplenc R (2013) Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer. J Pediatr 163(3):699–705 e691. https://doi.org/10.1016/j.jpeds.2013.01.062

    Article  PubMed  PubMed Central  Google Scholar 

  2. Boyle NM, Magaret A, Stednick Z, Morrison A, Butler-Wu S, Zerr D, Rogers K, Podczervinski S, Cheng A, Wald A, Pergam SA (2015) Evaluating risk factors for Clostridium difficile infection in adult and pediatric hematopoietic cell transplant recipients. Antimicrob Resist Infect Control 4(1):41. https://doi.org/10.1186/s13756-015-0081-4

    Article  PubMed  PubMed Central  Google Scholar 

  3. Castagnola E, Battaglia T, Bandettini R, Caviglia I, Baldelli I, Nantron M, Moroni C, Garaventa A (2009) Clostridium difficile-associated disease in children with solid tumors. Support Care Cancer 17(3):321–324. https://doi.org/10.1007/s00520-008-0507-0 [doi]

    Article  PubMed  Google Scholar 

  4. Dantes R, Epson EE, Dominguez SR, Dolan S, Wang F, Hurst A, Parker SK, Johnston H, West K, Anderson L, Rasheed JK, Moulton-Meissner H, Noble-Wang J, Limbago B, Dowell E, Hilden JM, Guh A, Pollack LA, Gould CV (2016) Investigation of a cluster of Clostridium difficile infections in a pediatric oncology setting. Am J Infect Control 44(2):138–145. https://doi.org/10.1016/j.ajic.2015.09.004

    Article  PubMed  Google Scholar 

  5. Dominguez SR, Dolan SA, West K, Dantes RB, Epson E, Friedman D, Littlehorn CA, Arms LE, Walton K, Servetar E, Frank DN, Kotter CV, Dowell E, Gould CV, Hilden JM, Todd JK (2014) High colonization rate and prolonged shedding of Clostridium difficile in pediatric oncology patients. Clin Infect Dis 59(3):401–403. https://doi.org/10.1093/cid/ciu302

    Article  PubMed  Google Scholar 

  6. Enoch DA, Butler MJ, Pai S, Aliyu SH, Karas JA (2012) Clostridium difficile in children: colonisation and disease. J Inf Secur 63(2):105–113. https://doi.org/10.1016/j.jinf.2011.05.016 [doi]

    Article  Google Scholar 

  7. Fisher BT, Sammons JS, Li Y, de Blank P, Seif AE, Huang YS, Kavcic M, Klieger S, Harris T, Torp K, Rheam D, Shah A, Aplenc R (2014) Variation in risk of hospital-onset Clostridium difficile infection across beta-lactam antibiotics in children with new-onset acute lymphoblastic leukemia. J Pediatric Infect Dis Soc 3(4):329–335. https://doi.org/10.1093/jpids/piu008

    Article  PubMed  PubMed Central  Google Scholar 

  8. Guzman-Cottrill JA, Ravin KA, Bryant KA, Zerr DM, Kociolek L, Siegel JD (2013) Infection prevention and control in residential facilities for pediatric patients and their families. Infect Control Hosp Epidemiol 34(10):1003–1041. https://doi.org/10.1086/673141

    Article  PubMed  Google Scholar 

  9. Joost I, Speck K, Herrmann M, von Muller L (2009) Characterisation of Clostridium difficile isolates by slpA and tcdC gene sequencing. Int J Antimicrob Agents 33(Suppl 1):S13–S18. https://doi.org/10.1016/s0924-8579(09)70010-x

    Article  PubMed  CAS  Google Scholar 

  10. Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, Hakim H, Santolaya M, Castagnola E, Davis BL, Dupuis LL, Gibson F, Groll AH, Gaur A, Gupta A, Kebudi R, Petrilli S, Steinbach WJ, Villarroel M, Zaoutis T, Sung L (2012) Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol 30(35):4427–4438. https://doi.org/10.1200/JCO.2012.42.7161 [doi]

    Article  PubMed  Google Scholar 

  11. Nicholson MR, Thomsen IP, Slaughter JC, Creech CB, Edwards KM (2015) Novel risk factors for recurrent Clostridium difficile infection in children. J Pediatr Gastroenterol Nutr 60(1):18–22. https://doi.org/10.1097/mpg.0000000000000553

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sammons JS, Localio R, Xiao R, Coffin SE, Zaoutis T (2013) Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis 57(1):1–8. https://doi.org/10.1093/cid/cit155

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sammons JS, Gerber JS, Tamma PD, Sandora TJ, Beekmann SE, Polgreen PM, Hersh AL (2014) Diagnosis and management of Clostridium difficile infection by pediatric infectious diseases physicians. J Pediatric Infect Dis Soc 3(1):43–48. https://doi.org/10.1093/jpids/pit065

    Article  PubMed  Google Scholar 

  14. Simon A, Ammann RA, Bode U, Fleischhack G, Wenchel HM, Schwamborn D, Gravou C, Schlegel P, Rutkowski S, Dannenberg C, Körholz D, Laws HJ, Kramer M (2008) Nosocomial infections in pediatric cancer patients: results of a prospective surveillance study from 7 university hospitals in Germany and Switzerland. BMC Infect Dis E-Pub (8):70

  15. Toltzis P, Kim J, Dul M, Zoltanski J, Smathers S, Zaoutis T (2009) Presence of the epidemic North American pulsed field type 1 Clostridium difficile strain in hospitalized children. J Pediatr 154(4):607–608. https://doi.org/10.1016/j.jpeds.2008.10.016 [doi]

    Article  PubMed  Google Scholar 

  16. Tschudin-Sutter S, Tamma PD, Milstone AM, Perl TM (2014) Predictors of first recurrence of Clostridium difficile infections in children. Pediatr Infect Dis J 33(4):414–416. https://doi.org/10.1097/inf.0000000000000108

    Article  PubMed  Google Scholar 

  17. Vendetti N, Zaoutis T, Coffin SE, Sammons JS (2015) Risk factors for in-hospital mortality among a cohort of children with Clostridium difficile infection. Infect Control Hosp Epidemiol 36(10):1183–1189. https://doi.org/10.1017/ice.2015.152

    Article  PubMed  Google Scholar 

  18. van Vliet MJ, Tissing WJ, Dun CA, Meessen NE, Kamps WA, de Bont ES, Harmsen HJ (2009) Chemotherapy treatment in pediatric patients with acute myeloid leukemia receiving antimicrobial prophylaxis leads to a relative increase of colonization with potentially pathogenic bacteria in the gut. Clin Infect Dis 49(2):262–270. https://doi.org/10.1086/599346 [doi]

    Article  PubMed  Google Scholar 

  19. van Vliet MJ, Harmsen HJ, de Bont ES, Tissing WJ (2010) The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog 6(5):e1000879. https://doi.org/10.1371/journal.ppat.1000879 [doi]

    Article  PubMed  PubMed Central  Google Scholar 

  20. von Muller L, Mock M, Halfmann A, Stahlmann J, Simon A, Herrmann M (2015) Epidemiology of Clostridium difficile in Germany based on a single center long-term surveillance and German-wide genotyping of recent isolates provided to the advisory laboratory for diagnostic reasons. Int J Med Microbiol 305(7):807–813. https://doi.org/10.1016/j.ijmm.2015.08.035

    Article  Google Scholar 

Download references

Acknowledgements

We thankfully acknowledge the outstanding work of the pediatric oncology team at the Children’s Hospital Medical Center, University of Saarland, Germany.

Author information

Authors and Affiliations

  1. Pediatric Oncology and Hematology, Saarland University Hospital, Saar, Homburg, Germany

    Arne Simon & Norbert Graf

  2. Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Kirrberger Straße, Gebäude 9 Saar, 66421, Homburg, Germany

    Arne Simon

  3. Institute of Medical Microbiology and Hygiene, National Consultant Laboratory for Clostridium difficile, University of Saarland Medical Centre, Homburg, Germany

    Markus Mock & Lutz von Müller

Authors
  1. Arne Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus Mock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Norbert Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lutz von Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AS and LvM designed the study, MM did the sampling of the clinical data, MM and LvM performed the laboratory investigations including ribotyping, and AS and NG wrote the draft of the manuscript, which has been finally consented by all authors.

Corresponding author

Correspondence to Arne Simon.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The study protocol was approved by the ethics committee of the medical association of Saarland, Germany (October 11, 2011; Ref. No. 206/11). Patients or their legal guardians gave informed consent during the prospective surveillance period. Since all clinical and laboratory data in the final dataset was analyzed anonymously, informed consent was not deemed necessary for the retrospective surveillance period.

Additional information

Communicated by Nicole Ritz

Electronic supplementary material

ESM 1

(DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Simon, A., Mock, M., Graf, N. et al. Investigation of Clostridium difficile ribotypes in symptomatic patients of a German pediatric oncology center. Eur J Pediatr 177, 403–408 (2018). https://doi.org/10.1007/s00431-017-3070-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-017-3070-1

Keywords

Search

Navigation