Clostridium (Clostridioides) difficile infections (CDIs) are among the most frequent healthcare-associated infections in Serbia. In 2013, Serbia participated in the European Clostridium difficile Infection Surveillance Network (ECDIS-Net) who launched a pilot study to enhance laboratory capacity and standardize surveillance for CDI. Two clinics of Clinical Center of Serbia [Clinic for Infectious and Tropical Diseases (CITD) and Clinic of Orthopedic Surgery and Traumatology (COT)] from Belgrade and one general hospital from another metropolitan area of Serbia, Užice, participated. During a period of 3 months in 2013, all patients with diagnosed CDI were included. The CDI incidence rates in CITD, COT, and General Hospital Užice were 19.0, 12.2, and 3.9 per 10,000 patient-days, respectively. In total, 49 patients were enrolled in the study with average age of 72 years. A complicated course of CDI was found in 14.3% of all patients. Six (12.2%) of 49 patients died, but not attributable to CDI. Of 39 C. difficile isolates, available for ribotyping, 78.9% belonged to ribotype 027; other PCR ribotypes were 001, 015, 002, 005, 010, 014, and 276. Antimicrobial susceptibility testing revealed low levels of MIC50 and MIC90 for metronidazole (0.5 μg/ml both) and vancomycin (0.25 and 0.5 μg/ml), while 28 strains of ribotype 027 were resistant to moxifloxacin with MIC ≥4 μg/ml. National surveillance is important to obtain more insight in the epidemiology of CDI and to compare the results with other European countries. This study by ECDIS-Net gives bases for a national surveillance of CDI in Serbia.
Barbut, F., Lalande, V., Daprey, G., Cohen, P., Marle, N., Burghoffer, B., Petit, J. C.: Usefulness of simultaneous detection of toxin A and glutamate dehydrogenase for the diagnosis of Clostridium difficile-associated diseases. Eur J Clin Microbiol Infect Dis 19, 481–484 (2000).
Smith, A.: Outbreak of Clostridium difficile infection in English hospital linked to hypertoxin-producing strains in Canada and US. Euro Surveill 10, E050630.2 (2005).
van Steenbergen, J., Debast, S., van Kregten, E., van den Berg, R., Notermans, D., Kuijper, E.: Isolation of Clostridium difficile ribotype 027, toxinotype III in the Netherlands after increase in C. difficile-associated diarrhoea. Euro Surveill 10, E050714.1 (2005).
Vonberg, R.-P., Schwab, F., Gastmeier, P.: Clostridium difficile in discharged inpatients, Germany. Emerg Infect Dis 13, 179–180 (2007).
Kuijper, E. J., Barbut, F., Brazier, J. S., Kleinkauf, N., Eckmanns, T., Lambert, M. L., Drudy, D., Fitzpatrick, F., Wiuff, C., Brown, D. J., Coia, J. E., Pituch, H., Reichert, P., Even, J., Mossong, J., Widmer, A. F., Olsen, K. E., Allerberger, F., Notermans, D. W., Delmée, M., Coignard, B., Wilcox, M., Patel, B., Frei, R., Nagy, E., Bouza, E., Marin, M., Åkerlund, T., Virolainen-Julkunen, A., Lyytikäinen, O., Kotila, S., Ingebretsen, A., Smyth, B., Rooney, P., Poxton, I. R., Monnet, D. L.: Update of Clostridium difficile infection due to PCR ribotype 027 in Europe. Euro Surveill 13, 18942 (2008).
Warny, M., Pepin, J., Fang, A., Killgore, G., Thompson, A., Brazier, J., Frost, E., McDonald, L. C.: Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366, 1079–1084 (2005).
Du Pont, H.: The search for effective treatment of Clostridium difficile infection. N Engl J Med 364, 473–475 (2011).
Lessa, F. C., Winston, L. G., McDonald, L. C., Emerging Infections Program C. difficile Surveillance Team: Burden of Clostridium difficile infection in the United States. N Engl J Med 372, 2369–2370 (2015).
Miller, B. A., Chen, L. F., Sexton, D. J., Anderson, D. J.: Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Infect Control Hosp Epidemiol 32, 387–390 (2011).
Bauer, M. P., Notermans, D. W., van Benthem, B. H., Brazier, J. S., Wilcox, M. H., Rupnik, M., Monnet, D. L., van Dissel, J. T., Kuijper, E. J., ECDIS Study Group: Clostridium difficile infection in Europe: A hospital-based survey. Lancet 377, 63–73 (2011).
Stojanovic, P., Kocic, B. D., Stojanovic, M. M., Miljkovic-Selimovic, B., Tasic, S. A., Miladinovic-Tasic, N. L., Babic, T. M.: Clinical importance and representation of toxigenic and non-toxigenic Clostridium difficile cultivated from stool samples of hospitalized patients. Braz J Microbiol 43, 215–223 (2012).
Šuljagić, V., Djordjević, D., Lazić, S., Mijović, B.: Epidemiological characteristics of nosocomial diarrhea caused by Clostridium difficile in a tertiary level hospital in Serbia. Srp Arh Celok Lek 141, 482–489 (2013).
Stojanovic, P.: Analysis of risk factors and clinical manifestations associated with Clostridium difficile disease in Serbian hospitalized patients. Braz J Microbiol 47, 902–910 (2016).
EUCAST: The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 4.0, 2014. Available at http://www.eucast.org/ast_of_bacteria/previous_versions_of_documents/
Field, A. P.: Non-parametric tests. In Field, A. P. (ed): Discovering Statistics Using SPSS, 2nd Edition. Sage Publications, London, 2005.
Šuljagić, V., Đorđević, D., Lazić, S., Mijović, B.: Epidemiological characteristics of nosocomial diarrhea caused by Clostridium difficile in a tertiary level hospital in Serbia. Srpski arhiv za celokupno lekarstvo 141, 482–489 (2013).
Kurti, Z., Lovasz, B. D., Mandel, M. D., Csima, Z., Golovics, P. A., Csako, B. D., Mohas, A., Gönczi, L., Gecse, K. B., Kiss, L. S., Szathmari, M., Lakatos, P. L.: Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe. World J Gastroenterol 21, 6728–6735 (2015).
Nyc, O., Krutova, M., Liskova, A., Matejkova, J., Drabek, J., Kuijper, E. J.: The emergence of Clostridium difficile PCR-ribotype 001 in Slovakia. Eur J Clin Microbiol Infect Dis 34, 1701–1708 (2015).
Rafila, A., Indra, A., Popescu, G. A., Wewalka, G., Allerberger, F., Benea, S., Badicut, I., Aschbacher, R., Huhulescu, S.: Occurrence of Clostridium difficile infections due to PCR ribotype 027 in Bucharest, Romania. J Infect Dev Countries 8, 694–698 (2014).
Popescu, G. A., Florea, D., Rafila, A.: Clostridium difficile is emerging in Romania: A story of 027 ribotype and excessive antibiotic consumption. J Gastrointestin Liver Dis 23, 342–343 (2014).
Obuch-Woszczatyński, P., Lachowicz, D., Schneider, A., Mól, A., Pawłowska, J., Ożdżeńska-Milke, E., Pruszczyk, P., Wultańska, D., Młynarczyk, G., Harmanus, C., Kuijper, E. J., van Belkum, A., Pituch, H.: Occurrence of Clostridium difficile PCR-ribotype 027 and it’s closely related PCR-ribotype 176 in hospitals in Poland in 2008–2010. Anaerobe 28, 13–17 (2014).
Starzengruber, P., Segagni Lusignani, L., Wrba, T., Mitteregger, D., Indra, A., Graninger, W., Presterl, E., Diab-Elschahaw, M.: Severe Clostridium difficile infection: Incidence and risk factors at a tertiary care university hospital in Vienna, Austria. Wien Klin Wochenschr 126, 427–430 (2014).
Oleastro, M., Coelho, M., Gião, M., Coutinho, S., Mota, S., Santos, A., Rodrigues, J., Faria, D.: Outbreak of Clostridium difficile PCR ribotype 027 – The recent experience of a regional hospital. BMC Infect Dis 14, 209 (2014).
van Dorp, S. M., Kinross, P., Gastmeier, P., Behnke, M., Kola, A., Delmée, M., Pavelkovich, A., Mentula, S., Barbut, F., Hajdu, A., Ingebretsen, A., Pituch, H., Macovei, I. S., Jovanović, M., Wiuff, C., Schmid, D., Olsen, K. E., Wilcox, M. H., Suetens, C., Kuijper, E. J., European Clostridium difficile Infection Surveillance Network (ECDIS-Net) on behalf of all participants: Standardised surveillance of Clostridium difficile infection in European acute care hospitals: A pilot study. Euro Surveill 21, 30293 (2016).
Morgan, O., Rodrigues, B., Elston, T., Verlander, N., Brown, D., Brazier, J., Reacher, M.: Clinical severity of Clostridium difficile PCR ribotype 027: A case-case study. PLoS One 3, e1812 (2008).
Nedelcu, I. N., Calistru, P. I., Ceausu, E.: Clostridium difficile associated disease: Burden of and predictors for in hospital fatal outcome. Results of a hospital-based study, Bucharest, Romania. Maedica (Buchar) 10, 97–100 (2015).
Popescu, G. A., Serban, R., Pistol, A., Niculcea, A., Preda, A., Lemeni, D., Macovei, I. S., Tălăpan, D., Rafila, A., Florea, D.: The recent emergence of Clostridium difficile infection in Romanian hospitals is associated with a high prevalence of polymerase chain reaction ribotype 027. Balkan Med J 35, 191–195 (2017).
Laza, R., Jurac, R., Crişan, A., Lăzureanu, V., Licker, M., Popovici, E. D., Bădiţoiu, L. M.: Clostridium difficile in western Romania: Unfavourable outcome predictors in a hospital for infectious diseases. BMC Infect Dis 15, 141 (2015).
Trifan, A., Cojocariu, C., Stoica, O., Stanciu, C.: The epidemiology of Clostridium difficile infection in Romania: What we know, or do not know and why? J Gastrointestin Liver Dis 23, 99–100 (2014).
Šuljagić, V., Miljković, I., Starčević, S., Stepić, N., Kostić, Z., Jovanović, D., Brusić-Renaud, J., Mijović, B., Šipetić-Grujičić, S.: Risk factors for Clostridium difficile infection in surgical patients hospitalized in a tertiary hospital in Belgrade, Serbia: A case-control study. Antimicrob Resist Infect Control 6, 31 (2017).