Diarrhea associated with Clostridium difficile in the oncology clinic

Purpose of the study. To conduct typing of toxigenic strains of Clostridium difficile, obtained from oncological patients who are in hospital.

Material and Methods. The study included 130 patients with Clostridium difficile – associated diarrhea. First, the presence of toxins A+B+ in the feces was determined by enzyme immunoassay on an automatic miniVidas analyzer from BioMieux SA (France). For screening using real-time PCR, 26 toxigenic Clostridium difficile were selected. For the study used the system GeneXpert company «Cepheid» (Sweden).

Results. Of the 1287 patients with diarrhea who were treated in an oncologic hospital, 130 (10,1%) tested positive for toxin A+B+ Clostridium difficile. For the study using real-time PCR, 26 samples were taken. The average age of patients is 57 years. 10 (38,5%) toxigenic strains were identified as hypervirulent ribotype. 7/10 strains were isolated for 3 consecutive month. The average age of patients with hypervirulent strains was 45 years. Patients participating in the study, in most cases were from the surgical departments – 61,5%, from the therapeutic – 34,7%.

Conclusion. The study showed that the prevalence of Clostridium difficile infection in our clinic is lower than in other countries. Although hypervirulent strains accounted for 1/3 of all typed Clostridium difficile, special attention should be paid to them. Delayed diagnosis, delay in the onset of specific therapy in cancer patients can lead to a deterioration in the quality of life and in some cases be fatal. PCR diagnostics can determine the hypervirulent ribotype and carry out epidemiological measures aimed at preventing local outbreaks in the hospital.

1. Soto L.U., Avila S.G., Alonso A.I.C., Mesones M.P.R., Garcia A.M.A., Lamadrid M.C.V.D. Clostridium difficile associated diarrhea: An increased problem. J Med.Clin.- 2016;147(12):543- 546 doi:10.1016/j.medcle.2016.12.043

2. Elliott B., Androga G.O., Knight D.R., Riley T.V. Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology. Infection, Genetics and Evolution, 49 (2017) 1-11 doi: 10.1016/j.meegid.2016.12.018

3. Costa L.C., Carvalho G.B.M., Gonzalez R.H., Gifoni M.A.C., Albuquerque Ribeiro R., Quesado-Gomez C., Castro Brito G.A. Molecular epidemiology of Clostridium difficile infection in a Brazilian cancer hospital. Anaerobe,48 (2017) 232- 236 doi: 10.1016/j.anaerobe.2017.10.001

4. Belousova E.A. Antibiotiko-associirovanny`e porazheniya kishechnika/E.A. Belousova// Rukovodstvo po medicinskoj mikrobiologii Tom 2/ red. A.S. Labinskaya, E.G.Volina, E.P. Kovaleva.- Moskva, 2014. – S. 284 – 289. (in Russian)

5. Nagy E. What do we know about the diagnostics, treatment and epidemiology of Clostridioides (Clostridium) difficile infection in Europe? /E.Nagy//J.Infect Chemother, 24(2018) 164-170 doi: 10.1016/j.jiac.2017.12.003

6. Cancado G.G.L., Silva R.O.S., Rupnik M., Nader A.P., Carvalho J.S., Mattos Paixao C.M., Resende B.A.M., Lobato F.C.F., Vileva E.G. Clinical epidemiology of Clostridium difficile infection among hospitalized patients with antibiotic-associated diarrhea in a university hospital of Brazil. Anaerobe, 54 (2018) 65-71 doi: 10.1016/j.anaerobe.2018.08.005

7. Janoir C. Virulence factors of Clostridium difficile and their role during infection. Anaerobe, 37 (2016) 13-24 doi: 10.1016/j.anaerobe.2015.10.009[http://www.antibiotic.ru/index.php?article=1302]

8. Shil`nikova I.I. Infekcii, associirovanny`e s Clostridium difficile /I.I. Shil`nikova, N.V. Dmitrieva, I.A. Klyuchnikova// Antimikrobnaya ximioterapiya vnutribol`nichny`x infekcij/ red.N.V. Dmitrieva, I.I. Petuxova. – Moskva, 2015. – S. 304 – 311. (in Russian)

9. Swati B., Dubberke E.R. Reprint of: Overview and changing epidemiology of Clostridium difficile infection. Seminars in Colon and Rectal Surgery, 29 (2018) 206-2011 doi: 10.1053/j.scrs.2018.11.001

10. Singh N., Klontz K. Clostridium difficile. In: Long S., Prober C., Fischer M., editors. Principles and Practice of Pediatric Infectioous Diseases, 5th ed.; 2018; ISBN: 9780323461320 doi: 10.1016/B 978-0-323-4018

11. Aktories K., Papatheodorou P., Schwan C. Binary Clostridium difficile toxin (CDT) – A virulence factor disturbing the cytoskeleton. Anaerobe, 53 (2018) 21-29 doi: 10.1016/j.anaerobe.2018.03.001

12. Lai C., Lin S., Tan C., Huang Y., Hsueh P. Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan. J Microbiol Immunol Infect, 47(2014) 491-496 doi: 10.1016/j.jmii.2013.06.007

13. Dmitrieva N.V. Rasprostranennost` Clostridium difficile – associirovannoj diarei u gospitalizirovanny`x bol`ny`x (rezul`taty` rossijskogo prospektivnogo mnogocentrovogo issledovaniya) /N.V. Dmitrieva [i dr.]// Klinicheskaya mikrobiologiya i antimikrobnaya ximioterapiya. 2017; 19(4). S.268-274 (in Russian)

14. Lagier J. Gut microbiota and Clostridium difficile infections. Human Microbiome Journal, 2 (2016) 10-14. doi: 10.1016/j.humic.2016.10.003

15. Daniel A., Rapose A. The evaluation of Clostridium difficile infection (CDI) in a community hospital. Journal of Infection and Public Health, 8 (2015) 155-160 doi: 10.1016/j. jiph.2014.08.002

16. Tkhawkho L., Nitzan O., Pastukh N., Brodsky D., Jackson K., Peretz A. Antimicrobial susceptibility of Clostridium difficile isolates in Israel. Journal of Global Antimicrobial Resistance, 10 (2017) 161-164 doi: 10.1016/j.jgar.2017.04.005

17. Hung Y., Lee J., Lin H., Liu H., Wu Y., Tsai P., Ko W. Clinical impact of Clostridium difficile colonization. J Microbiol Immunol Infect, 48 (2015) 241-248 doi: 10.1016/j.jmii.2014.04.011

18. Barker A.K., Zellmer C., Tischenolorf J., Duster M., Valentine S., Wright M.O., Safdar N. On the hands of patients with Clostridium difficile: A study of spore prevalence and effect of hand hygiene on C.difficile removal. American Journal of Infection Control, 45 (2017) 1154-1156 doi: 10.1016/j.ajic.2017.03.005

19. Fraga E.G., Nicodemo A.C., Sampaio J.L.M. Antimicrobial susceptibility of Brazilian Clostridium difficile strains determined by agar dillution and disk diffusion. The Brazilian Journal of Infectious Diseases 2016; 20(5); 476-481 doi: 10.1016/j.bjid.2016.07.004

20. Hensgens M.P.M., Dekkers O.M., Demeulemeester A., Buiting A.G.M., Bloembergen P., van Benthem B.H.B., Le Cessie S., Kuijper E.J. Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a rested case-control study. Clinical Microbiology and Infection, 20(2014) 01067-01074 doi: 10.1111/1469-0691.12758

21. Chang G.Y., Dembry L.M., Banach D.B. Epidemiology of Clostridium difficile infection in hospitalized oncology patients. American Journal of Infection Control, 44(2016) 1408- 1410 doi: 10.1016/j.ajic.2016.04.210

22. Jovanovic M., Drakulovic M., Tosic T., Stosovic R., Jovanovic S. Occurrence of Clostridium difficile infections in Serbia and high proportion of PCR ribotype 027 strains in two hospitals in Belgrade. Anaerobe, 51(2018) 64-67 doi: 10.1016/j.anaerobe.2018.04.005