Clostridioides difficile Infection in Patients with Chronic Kidney Disease: A Systematic Review

Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.

[1]  L. Diebel,et al.  Clostridioides difficile in COVID-19 Patients, Detroit, Michigan, USA, March–April 2020 , 2020, Emerging infectious diseases.

[2]  N. L. Rukavina Mikusic,et al.  Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis , 2020, Pflügers Archiv - European Journal of Physiology.

[3]  Bangmao Wang,et al.  Fecal microbiota transplantation in cancer management: Current status and perspectives , 2018, International journal of cancer.

[4]  Myung-Gyu Kim,et al.  Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  K. Carroll,et al.  Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  A. Delgado,et al.  Poorer outcomes among cancer patients diagnosed with Clostridium difficile infections in United States community hospitals , 2017, BMC Infectious Diseases.

[7]  A. Rösler,et al.  Asymptomatic and yet C. difficile-toxin positive? Prevalence and risk factors of carriers of toxigenic Clostridium difficile among geriatric in-patients , 2016, BMC Geriatrics.

[8]  Peter T. McKenney,et al.  Clostridium difficile colitis: pathogenesis and host defence , 2016, Nature Reviews Microbiology.

[9]  A. Więcek,et al.  The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics , 2015, Nutrients.

[10]  S. Erickson,et al.  Chronic kidney disease and end‐stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta‐analysis , 2015, International journal of clinical practice.

[11]  C. Thongprayoon,et al.  The Risks of Incident and Recurrent Clostridium difficile-Associated Diarrhea in Chronic Kidney Disease and End-Stage Kidney Disease Patients: A Systematic Review and Meta-Analysis , 2015, Digestive Diseases and Sciences.

[12]  A. Gasbarrini,et al.  Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection , 2015, Alimentary pharmacology & therapeutics.

[13]  H. Qu,et al.  Clostridium difficile infection in diabetes. , 2014, Diabetes research and clinical practice.

[14]  A. van Belkum,et al.  First Polish outbreak of Clostridium difficile ribotype 027 infections among dialysis patients , 2014, European Journal of Clinical Microbiology & Infectious Diseases.

[15]  T. Riley,et al.  Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. , 2014, The Journal of antimicrobial chemotherapy.

[16]  David M Aronoff,et al.  Epidemiology of Clostridium difficile Infection , 2013, Journal of pharmacy practice.

[17]  Mark A. Miller,et al.  Renal Impairment and Clinical Outcomes of Clostridium difficile Infection in Two Randomized Trials , 2013, American Journal of Nephrology.

[18]  H. C. Beck,et al.  Anchorless surface associated glycolytic enzymes from Lactobacillus plantarum 299v bind to epithelial cells and extracellular matrix proteins. , 2013, Microbiological research.

[19]  L. Baddour,et al.  Clostridium difficile infection in patients with chronic kidney disease. , 2012, Mayo Clinic proceedings.

[20]  T. Louie,et al.  Fidaxomicin Preserves the Intestinal Microbiome During and After Treatment of Clostridium difficile Infection (CDI) and Reduces Both Toxin Reexpression and Recurrence of CDI , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  Fernanda C. Lessa,et al.  Current Status of Clostridium difficile Infection Epidemiology , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  D. Slymen,et al.  Risk factors associated with complications and mortality in patients with Clostridium difficile infection. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  A. Manges,et al.  Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  B. Wren,et al.  Hypervirulent Clostridium difficile PCR-Ribotypes Exhibit Resistance to Widely Used Disinfectants , 2011, PloS one.

[25]  T. Louie,et al.  A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. , 2010, Microbiology.

[26]  A. Stang Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses , 2010, European Journal of Epidemiology.

[27]  S. Chasan-Taber,et al.  Results of a phase Iii trial comparing tolevamer, vancomycin and metronidazole in patients with Clostridium difficile-associated diarrhoea , 2008 .

[28]  L. Mascola,et al.  Increase in Clostridium difficile–related Mortality Rates, United States, 1999–2004 , 2007, Emerging infectious diseases.

[29]  M. Wilcox,et al.  Efficacy of Hospital Cleaning Agents and Germicides Against Epidemic Clostridium difficile Strains , 2007, Infection Control & Hospital Epidemiology.

[30]  S. Sattar,et al.  Activity of selected oxidizing microbicides against the spores of Clostridium difficile: relevance to environmental control. , 2005, American journal of infection control.

[31]  J. Pépin,et al.  Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  S. Ahrné,et al.  Probiotic strains of Lactobacillus and Bifidobacterium affect the translocation and intestinal load of Enterobacteriaceae differently after D-galactosamine-induced liver injury in rats , 2005 .

[33]  Louis Valiquette,et al.  Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity , 2004, Canadian Medical Association Journal.

[34]  B. Birkenfeld,et al.  A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome , 2001, European journal of gastroenterology & hepatology.

[35]  C. Bassi,et al.  Lactobacillus plantarum Reduces Infection of Pancreatic Necrosis in Experimental Acute Pancreatitis , 2001, Digestive Surgery.

[36]  S. Ahrné,et al.  Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome , 2000, American Journal of Gastroenterology.

[37]  Wold,et al.  The normal Lactobacillus flora of healthy human rectal and oral mucosa , 1998, Journal of applied microbiology.

[38]  B. Jeppsson,et al.  Effect of Lactobacillus supplementation with and without arginine on liver damage and bacterial translocation in an acute liver injury model in the rat , 1997, Hepatology.

[39]  A. Glatt,et al.  Clostridium difficile infection associated with antineoplastic chemotherapy: a review. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  S. Ahrné,et al.  Numerical taxonomy of Lactobacillus spp. associated with healthy and diseased mucosa of the human intestines. , 1993, The Journal of applied bacteriology.

[41]  P. Stenvinkel,et al.  Clostridium difficile infection--a poor prognostic sign in uremic patients? , 1992, Clinical nephrology.

[42]  Jiaquan Xu,et al.  Deaths: preliminary data for 2008. , 2010, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[43]  P. Mangell On Lactobacillus plantarum 299v, bacterial translocation and intestinal permeability. , 2007 .