Back
 JBM  Vol.7 No.2 , February 2019
Association of Clostridium difficile with Antibiotic Associated Diarrhea among Hospitalized Children in Diyala-Iraq
Abstract: Background: Clostridium difficile infection (CDI) is an increasingly important cause of morbidity in hospitalized children. Absence of clinical suspicion and suboptimum laboratory diagnostic methods are behind the misdiagnosed infections. Objectives: To determine the association of Cl. difficle infection among hospitalized children suspected of having antibiotic associated diarrhea (AAD) plus detection of the bacterium’s toxins A and B and the enzyme glutamate dehydrogenase (GDH). Patients and methods: This cross-sectional study was conducted in Al-Batool Hospital for Maternity and Children in Baquba City for the period from March 2017 to April 2018. Sixty stool samples were collected from children inpatients. The age range was 15 days up to one year. 41 (68.3%) and 19 (31.7%) were males and females respectively. Additionally, 20 healthy children were enrolled as control group. The age range was 50 days up to one year, 12 (60%) and 8 (40%) were males and females respectively. Special questionnaire was preconstructed for collection of demographic information. Isolation of Cl. difficile was carried out on Colombia blood agar and tryptose sulfite cycloserine agar. Enzyme linked immunosorband assays were used for the detection of toxin A and B (CerTest-Biotec, Spain), and for the detection of glutamate dehydrogenase enzyme (CerTest-Biotec, Spain). Human privacy was respected by obtaining the parents’ oral consent. Statistical analyses were done using SPSS Version 18 and P values less than 0.05 were considered significant. Results: The isolation rate of Cl. difficile form patients and healthy children was 11.7% and 5% respectively. The toxins detection rate among patients was 23.3%, of these 35.7% for toxin A, and 64.3% for toxin A and B together. Neither of the patients’ specimens was positive for toxin B alone, nor was healthy control positive for all toxins. The overall detection rate of GDH enzyme in study groups was 32.5%, with a significantly higher among patients as compared to control (28.8% vs. 3.8% , P = 0.045). The isolation and detection rate of Cl. difficile were increased as the time of the onset of diarrhea was increased. Other factors: age, sex, residence, and type of feeding were insignificantly affecting the isolation and detection rate of Cl. difficile by different techniques. The third generation cephalosporines either singly or in combinations with each other or with another antibiotic were mostly associated with the higher rates of diarrhea. Conclusion: Cl. difficile infection is associated with about one third of antibiotic associated diarrhea among hospitalized children one year of age in Diyala province. CDI should be included in the routine differential diagnoses for hospitalized children presenting with AAD.
Cite this paper: Hasan, A. , Al-Zubaidi, R. and Al-Duliami, A. (2019) Association of Clostridium difficile with Antibiotic Associated Diarrhea among Hospitalized Children in Diyala-Iraq. Journal of Biosciences and Medicines, 7, 64-73. doi: 10.4236/jbm.2019.72006.
References

[1]   Samady, W., Pong, A. and Fisher, E. (2014) Risk Factors for the Development of Clostridium difficile Infection in Hospitalized Children. Current Opinion in Pediatrics, 26, 568-572.
https://doi.org/10.1097/MOP.0000000000000126

[2]   Leffler, D.A. and Lamont, J.T. (2015) Clostridium difficile Infection. New England Journal of Medicine, 372, 1539-1548.
https://doi.org/10.1056/NEJMra1403772

[3]   Krutova, M., Kinross, P., Barbut, F., Hajdu, A., Wilcox, M.H. and Kuijper, E.J. (2018) Survey Contributors. How to: Surveillance of Clostridium difficile Infections. Clinical Microbiology and Infection, 24, 469-475.
https://doi.org/10.1016/j.cmi.2017.12.008

[4]   Lessa, F.C., Mu, Y., Bamberg, W.M., Beldavs, Z.G., Dunn, J.R., Farley, M.M., Holzbauer, S.M., Meek, J.I., Phipps, E.C., Wilson, L.E., Winston, L.G., Cohen, J.A., Limbago, B.M., Fridkin, S.K., Gerding, D.N. and McDonald, L.C. (2015) Burden of Clostridium difficile Infection in the United States. New England Journal of Medicine, 372, 825-834.
https://doi.org/10.1056/NEJMoa1408913

[5]   Chilton, C.H., Pickering, D.S. and Freeman, J. (2018) Microbiologic Factors Affecting Clostridium difficile Recurrence. Clinical Microbiology and Infection, 24, 476-482.
https://doi.org/10.1016/j.cmi.2017.11.017

[6]   Hopkins, C.J. (2014) Inpatient Antibiotic Consumption in a Regional Secondary Hospital in New Zealand. Internal Medicine Journal, 44, 185-190.
https://doi.org/10.1111/imj.12345

[7]   Ianiro, G., Tilg, H. and Gasbarrini, A. (2016) Antibiotics as Deep Modulators of Gut Microbiota: Between Good and Evil. Gut, 65, 1906-1915.
https://doi.org/10.1136/gutjnl-2016-312297

[8]   Pant, C., Anderson, M.P., Deshpande, A., Altaf, M.A., Grunow, J.E., Atreja, A. and Sferra, T.J. (2013) Health Care Burden of Clostridium difficile Infection in Hospitalized Children with Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 19, 1080-1085.
https://doi.org/10.1097/MIB.0b013e3182807563

[9]   Hourigan, S.K., Oliva-Hemker, M. and Hutfless, S. (2014) The Prevalence of Clostridium difficile Infection in Pediatric and Adult Patients with Inflammatory Bowel Disease. Digestive Diseases and Sciences, 59, 2222-2227.
https://doi.org/10.1007/s10620-014-3169-4

[10]   van Beurden, Y.H., Nezami, S., Mulder, C.J.J. and Vandenbroucke-Grauls, C.M.J.E. (2018) Host Factors Are More Important in Predicting Recurrent Clostridium difficile Infection than Ribotype and Use of Antibiotics. Clinical Microbiology and Infection, 24, 85.e1-85.e4.
https://doi.org/10.1016/j.cmi.2017.07.025

[11]   Silva, R.O., Rupnik, M., Diniz, A.N., Vilela, E.G. and Lobato, F.C. (2015) Clostridium difficile Ribotypes in Humans and Animals in Brazil. Memórias do Instituto Oswaldo Cruz, 110, 1062-1065.
https://doi.org/10.1590/0074-02760150294

[12]   Kachrimanidou, M. and Malisiovas, N. (2011) Clostridium difficile Infection: A Comprehensive Review. Critical Reviews in Microbiology, 37, 178-187.
https://doi.org/10.3109/1040841X.2011.556598

[13]   Elliott, B., Androga, G.O., Knight, D.R. and Riley, T.V. (2017) Clostridium difficile Infection: Evolution, Phylogeny and Molecular Epidemiology. Infection, Genetics and Evolution, 49, 1-11.
https://doi.org/10.1016/j.meegid.2016.12.018

[14]   Taori, S.K., Wroe, A., Hardie, A., Gibb, A.P. and Poxton, I.R. (2014) A Prospective Study of Community-Associated Clostridium difficile Infections: The Role of Antibiotics and Co-Infections. Journal of Infection, 69, 134-144.
https://doi.org/10.1016/j.jinf.2014.04.002

[15]   Davies, K.A., Longshaw, C.M., Davis, G.L., Bouza, E., Barbut, F., Barna, Z., Delmee, M., Fitzpatrick, F., Ivanova, K., Kuijper, E., Macovei, I., Mentula, S., Mastrantonio, P., von Müller, L., Oleastro, M., Petinaki, E., Pituch, H., Noren, T., Novakova, E., Nyc, O., Rupnik, M., Schmid, D. and Wilcox, M.H. (2014) Underdiagnosis of Clostridium difficile across Europe: The European, Multicentre, Prospective, Biannual, Point-Prevalence Study of Clostridium difficile Infection in Hospitalised Patients with Diarrhoea (EUCLID). The Lancet Infectious Diseases, 14, 1208-1219.
https://doi.org/10.1016/S1473-3099(14)70991-0

[16]   Kola, A., Wiuff, C., Akerlund, T., van Benthem, B.H., Coignard, B., Lyytikainen, O., Weitzel-Kage, D., Suetens, C., Wilcox, M.H., Kuijper, E.J., Gastmeier, P. and Members of ECDIS-Net (2016) Survey of Clostridium difficile Infection Surveillance Systems in Europe, 2011. Euro Surveillance, 21, 21-29.
https://doi.org/10.2807/1560-7917.ES.2016.21.29.30291

[17]   Koo, H.L., Van, J.N., Zhao, M., et al. (2014) Real Time Polymerase Chain Reaction Detection of Asymptomatic Clostridium difficile Colonization and Rising C. difficile-Associated Disease Rates. Infection Control & Hospital Epidemiology, 35, 667-673.
https://doi.org/10.1086/676433

[18]   Spigaglia, P., Barbanti, F., Castagnola, E., Diana, M.C., Pescetto, L. and Bandettini, R. (2017) Clostridium difficile Causing Pediatric Infections: New Findings from a Hospital-Based Study in Italy. Anaerobe, 48, 262-268.
https://doi.org/10.1016/j.anaerobe.2017.10.008

[19]   Gateau, C., Couturier, J., Coia, J. and Barbut, F. (2018) How to: Diagnose Infection Caused by Clostridium difficile. Clinical Microbiology and Infection, 24, 463-468.
https://doi.org/10.1016/j.cmi.2017.12.005

[20]   Luna, R.A., Boyanton, B.L., Mehta, S., Courtney, E.M., Webb, C.R., Revell, P.A. and Versalovic, J. (2011) Rapid Stool-Based Diagnosis of Clostridium difficile Infection by Real-Time PCR in a Children’s Hospital. Journal of Clinical Microbiology, 49, 851-857.
https://doi.org/10.1128/JCM.01983-10

[21]   Zhou, F.F., Wu, S., Klena, J.D. and Huang, H.H. (2014) Clinical Characteristics of Clostridium difficile Infection in Hospitalized Patients with Antibiotic-Associated Diarrhea in a University Hospital in China. European Journal of Clinical Microbiology & Infectious Diseases, 33, 1773-1779.
https://doi.org/10.1007/s10096-014-2132-9

[22]   Tattevin, P., Buffet-Bataillon, S., Donnio, P.Y., Revest, M. and Michelet, C. (2013) Clostridium difficile Infections: Do We Know the Real Dimensions of the Problem? International Journal of Antimicrobial Agents, 42, S36-S40.
https://doi.org/10.1016/j.ijantimicag.2013.04.009

[23]   Wiedel, N., Gilbert, J., Baloun, B. and Nelson, C. (2016) Clostridium difficile Associated Diarrhea. South Dakota Medicine, 69, 124-127.

[24]   Shin, J.H., Chaves-Olarte. E. and Warren, C.A. (2016) Clostridium difficile Infection. In: Scheld, W., Hughes, J. and Whitley, R., Eds., Emerging Infections 10, ASM Press, Washington, DC.
https://doi.org/10.1128/microbiolspec.EI10-0007-2015

[25]   Jonathan, D., Crews, J.D., Koo, H.L., Jiang, Z., Starke, J.R. and DuPont, H.L. (2014) A Hospital-Based Study of the Clinical Characteristics of Clostridium difficile Infection in Children. Pediatric Infectious Disease Journal, 33, 924-928.
https://doi.org/10.1097/INF.0000000000000338

[26]   McFarland, L.V., Ozen, M., Dinleyici, E.C. and Goh, S. (2016) Comparison of Pediatric and Adult Antibiotic-Associated Diarrhea and Clostridium difficile Infections. World Journal of Gastroenterology, 22, 3078-3104.
https://doi.org/10.3748/wjg.v22.i11.3078

[27]   Russello, G., Russo, A., Sisto, F., Scaltrito, M.M. and Farina, C. (2012) Laboratory Diagnosis of Clostridium difficile Associated Diarrhoea and Molecular Characterization of Clinical Isolates. New Microbiologica, 35, 307-316.

[28]   Rene, P., Frenette, C.P., Schiller, I., Dendukuri, N., Brassard, P, Fenn, S. and Loo, V.G. (2012) Comparison of Eight Commercial Enzyme Immunoassays for the Detection of Clostridium difficile from Stool Samples and Effect of Strain Type. Diagnostic Microbiology and Infectious Disease, 73, 94-96.
https://doi.org/10.1016/j.diagmicrobio.2012.01.005

[29]   Mattner, F., Winterfeld, I. and Mattner, L. (2012) Diagnosing Toxigenic Clostridium difficile: New Confidence Bounds Show Culturing Increases Sensitivity of the Toxin A/B Enzyme Immunoassay and Refute Gold Standards. Scandinavian Journal of Infectious Diseases, 44, 578-585.
https://doi.org/10.3109/00365548.2012.655772

[30]   Alfa, M.J. and Sepehri, S. (2013) Combination of Culture, Antigen and Toxin Detection, and Cytotoxin Neutralization Assay for Optimal Clostridium difficile Diagnostic Testing. Canadian Journal of Infectious Diseases and Medical Microbiology, 24, 89-92.
https://doi.org/10.1155/2013/934945

[31]   Krutova, M., Matejkova, J., Zajac, M., Hubacek, P. and Nyc, O. (2014) Diagnosis of Clostridium difficile Infections: Comparative Study of Two Immuno Enzyme Assays with Confirmation by PCR and Culture Followed by PCR Ribotyping. Epidemiologie, Mikrobiologie, Imunologie, 63, 99-102.

[32]   Loo, V.G., Bourgault, A.M., Poirier, L., Lamothe, F., Michaud, S., Turgeon, N., Toye, B., Beaudoin, A., Frost, E.H., Gilca, R., Brassard, P., Dendukuri, N., Beliveau, C., Oughton, M., Brukner, I. and Dascal, A. (2011) Host and Pathogen Factors for Clostridium difficile Infection and Colonization. New England Journal of Medicine, 365, 1693-1703.
https://doi.org/10.1056/NEJMoa1012413

[33]   Kaneria, M.V. and Paul, S. (2012) Incidence of Clostridium difficile Associated Diarrhoea in a Tertiary Care Hospital. Journal of the Association of Physicians of India, 60, 26-28.

[34]   Duleba, K., Pawlowska, M. and Wietlicka-Piszcz, M. (2014) Clostridium difficile Infection in Children Hospitalized Due to Diarrhea. European Journal of Clinical Microbiology & Infectious Diseases, 33, 201-209.
https://doi.org/10.1007/s10096-013-1946-1

[35]   Talpaert, M.J., Gopal Rao, G., Cooper, B.S. and Wade, P. (2011) Impact of Guidelines and Enhanced Antibiotic Stewardship on reducing Broad-Spectrum Antibiotic Usage and Its Effect on Incidence of Clostridium difficile Infection. Journal of Antimicrobial Chemotherapy, 66, 2168-2174.
https://doi.org/10.1093/jac/dkr253

[36]   Crews, J.D., Anderson, L.R., Waller, D.K., Swartz, M.D., DuPont, H.L. and Starke, J.R. (2015) Risk Factors for Community-Associated Clostridium difficile-Associated Diarrhea in Children. Pediatric Infectious Disease Journal, 34, 919-923.
https://doi.org/10.1097/INF.0000000000000767

[37]   Balassiano, I.T., Yates, E.A., Domingues, R.M. and Ferreira, E.O. (2012) Clostridium difficile: A Problem of Concern in Developed Countries and Still a Mystery in Latin America. Journal of Medical Microbiology, 61, 169-179.
https://doi.org/10.1099/jmm.0.037077-0

[38]   Aldeyab, M.A., Kearney, M.P., Scott, M.G., Aldiab, M.A., Alahmadi, Y.M., Darwish Elhajji, F.W., Magee, F.A. and McElnay, J.C. (2012) An Evaluation of the Impact of Antibiotic Stewardship on Reducing the Use of High-Risk Antibiotics and Its Effect on the Incidence of Clostridium difficile Infection in Hospital Settings. Journal of Antimicrobial Chemotherapy, 67, 2988-2996.
https://doi.org/10.1093/jac/dks330

 
 
Top