Clostridioides difficile Infection, Still a Long Way to Go
Abstract
:1. Introduction
2. Epidemiology
3. Diagnosis and Microbiology
3.1. Why Are We Not Using NAAT as the Ultimate Tool for CDI Diagnosis?
3.2. Could Quantitative NAAT Be Used to Predict Clinical Outcome?
3.3. Why Do We Not Routinely Perform Antibiotic Susceptibility Testing (AST) for CDI?
3.4. Are We over- or Underdiagnosing CDI?
3.5. So Where Exactly Is the Problem?
- Accurate CDI diagnosis cannot be achieved with a single assay.
- NAAT, as a standalone test, is not appropriate to provide an adequate clinical PPV with low CDI prevalence, although some controversy remains.
- The recommended two- to three-step algorithms combining EIA/LFA, NAAT and TC proposed by the ESCMID guideline is a diagnostic improvement but is insufficient to cover with high PPV and NPV the complex spectrum of CDI clinical presentations and transmission. Nevertheless, EIA/LFA toxin assays should be avoided due to relatively low sensitivity.
- Even though the role of C. difficile is increasingly being recognized in the community, this diagnosis is not systematically suspected in the community setting and in the absence of traditional risk factors.
- More population-based studies are required to better appreciate the true burden of disease in the community.
- There is a need to provide specific recommendations for testing for C. difficile in patients with diarrhea outside the hospital and an increase in physicians’ awareness.
4. Definitions and Endpoints
4.1. What Does Severe Infection Mean?
4.2. What Is an Adequate Endpoint?
5. Treatment
5.1. Antibiotic Treatment
5.1.1. Mild/Moderate and Severe Forms
5.1.2. Complicated Forms
5.1.3. Recurrences
5.2. Surgery
5.3. Monoclonal Antibodies
5.4. Fecal Microbiota Transplantation (FMT)
5.5. Why Is Long-Term Follow up after FMT Recommended?
- What is the definition of severe infection?
- What is the optimal clinical endpoint for studies?
- In complicated forms, what is the best antibiotic treatment?
- Is extended-pulsed fidaxomicin superior to classic 10 days fidaxomicin administration or pulsed vancomycin?
- What are the selection criteria to choose between loop ileostomy versus total or subtotal colectomy?
- Can FMT be proposed earlier, after the first recurrence?
- In a high recurrence risk patient is it more efficient and/or cost-efficient to propose bezlotoxumab or fidaxomicin?
- Could bezlotoxumab be proposed to avoid FMT in specific populations or where FMT is not available?
- In FMT, what is the best way to deliver the transplant, upper or lower?
- Determine the mechanism associated with the efficacy of FMT is crucial to unveil other potential options for treatment.
- Long-term follow-up of both donors and recipients after FMT with registries at a national level is required.
6. Prevention
6.1. Prevention and Antibiotic Exposure
6.2. Asymptomatic Carriage and Potential Dissemination
6.3. Could the Identification of Carriers Be an Effective Preventive Strategy for HA-CDI?
- What is the best preventive regimen to prevent CDI recurrence in patients with an initial episode exposed to systemic antibiotics?
- The significance of asymptomatic carrier status for the individual patient and their environment in the short term and in the long term as well as their role in hospital transmission is not yet elucidated.
- There seems to be a potential role of screening for colonization in selected settings and patients upon admission to prevent HA-CDI but more studies are required to better support this strategy.
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Bauer, M.P.; Notermans, D.W.; Van Benthem, B.H.B.; Brazier, J.S.; Wilcox, M.H.; Rupnik, M.; Monnet, D.L.; Van Dissel, J.T.; Kuijper, E.J. Clostridium difficile infection in Europe: A hospital-based survey. Lancet 2011, 377, 63–73. [Google Scholar] [CrossRef]
- Zarb, P.; Coignard, B.; Griskeviciene, J.; Muller, A.; Vankerckhoven, V.; Weist, K.; Goossens, M.M.; Vaerenberg, S.; Hopkins, S.; Catry, B.; et al. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. Eurosurveillance 2012, 17, 20316. [Google Scholar] [CrossRef] [PubMed]
- Lessa, F.C.; Mu, Y.; Bamberg, W.M.; Beldavs, Z.G.; Dumyati, G.K.; Dunn, J.R.; Farley, M.M.; Holzbauer, S.M.; Meek, J.I.; Phipps, E.C.; et al. Burden of Clostridium difficile Infection in the United States. N. Engl. J. Med. 2015, 372, 825–834. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuijper, E.J.; Barbut, F.; Brazier, J.S.; Kleinkauf, N.; Eckmanns, T.; Lambert, M.L.; Drudy, D.; Fitzpatrick, F.; Wiuff, C.; Brown, D.J.; et al. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Eurosurveillance 2008, 13. [Google Scholar]
- Loo, V.G.; Poirier, L.; Miller, M.A.; Oughton, M.; Libman, M.D.; Michaud, S.; Bourgault, A.-M.; Nguyen, T.; Frenette, C.; Kelly, M.; et al. A Predominantly Clonal Multi-Institutional Outbreak ofClostridium difficile–Associated Diarrhea with High Morbidity and Mortality. N. Engl. J. Med. 2005, 353, 2442–2449. [Google Scholar] [CrossRef] [Green Version]
- 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 2005, 366, 1079–1084. [Google Scholar] [CrossRef]
- Gould, C.V.; Edwards, J.R.; Cohen, J.; Bamberg, W.M.; Clark, L.A.; Farley, M.M.; Johnston, H.; Nadle, J.; Winston, L.; Gerding, D.N.; et al. Effect of nucleic acid amplification testing on population-based incidence rates of Clostridium difficile infection. Clin. Infect. Dis. 2013, 57, 1304–1307. [Google Scholar] [CrossRef] [Green Version]
- Moehring, R.W.; Lofgren, E.; Anderson, D.J. Impact of Change to Molecular Testing for Clostridium difficile Infection on Healthcare Facility–Associated Incidence Rates. Infect. Control. Hosp. Epidemiol. 2013, 34, 1055–1061. [Google Scholar] [CrossRef] [Green Version]
- Fekety, R.; McFarland, L.V.; Surawicz, C.M.; Greenberg, R.N.; Elmer, G.W.; Mulligan, M.E. Recurrent Clostridium difficile diarrhea: Characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin. Infect. Dis. 1997, 24, 324–333. [Google Scholar] [CrossRef]
- McFarland, L.V.; Surawicz, C.M.; Rubin, M.; Fekety, R.; Elmer, G.W.; Greenberg, R.N. Recurrent Clostridium Difficile Disease: Epidemiology and Clinical Characteristics. Infect. Control. Hosp. Epidemiol. 1999, 20, 43–50. [Google Scholar] [CrossRef]
- Guh, A.Y.; Mu, Y.; Winston, L.G.; Johnston, H.; Olson, D.; Farley, M.M.; Wilson, L.E.; Holzbauer, S.M.; Phipps, E.C.; Dumyati, G.K.; et al. Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N. Engl. J. Med. 2020, 382, 1320–1330. [Google Scholar] [CrossRef] [PubMed]
- Suetens, C.; Latour, K.; Kärki, T.; Ricchizzi, E.; Kinross, P.; Moro, M.L.; Jans, B.; Hopkins, S.; Hansen, S.; Lyytikäinen, O.; et al. Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: Results from two European point prevalence surveys, 2016 to 2017. Eurosurveillance 2018, 23, 1800516. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wilcox, M.H.; Shetty, N.; Fawley, W.N.; Shemko, M.; Coen, P.; Birtles, A.; Cairns, M.; Curran, M.D.; Dodgson, K.J.; Green, S.M.; et al. Changing Epidemiology of Clostridium difficile Infection Following the Introduction of a National Ribotyping-Based Surveillance Scheme in England. Clin. Infect. Dis. 2012, 55, 1056–1063. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Goorhuis, A.; Bakker, D.; Corver, J.; Debast, S.B.; Harmanus, C.; Notermans, D.W.; Bergwerff, A.A.; Dekker, F.W.; Kuijper, E.J. Emergence ofClostridium difficileInfection Due to a New Hypervirulent Strain, Polymerase Chain Reaction Ribotype 078. Clin. Infect. Dis. 2008, 47, 1162–1170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Crobach, M.J.T.; Dekkers, O.M.; Wilcox, M.H.; Kuijper, E.J. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): Data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin. Microbiol. Infect. 2009, 15, 1053–1066. [Google Scholar] [CrossRef] [Green Version]
- McDonald, L.C.; Gerding, D.N.; Johnson, S.; Bakken, J.S.; Carroll, K.C.; Coffin, S.E.; Dubberke, E.R.; Garey, K.W.; Gould, C.V.; Kelly, C.; 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). Clin. Infect. Dis. 2018, 66, 987–994. [Google Scholar] [CrossRef]
- Planche, T.; Wilcox, M. Reference assays for Clostridium difficile infection: One or two gold standards? J. Clin. Pathol. 2010, 64, 1–5. [Google Scholar] [CrossRef] [Green Version]
- Crobach, M.; Planche, T.; Eckert, C.; Barbut, F.; Terveer, E.M.; Dekkers, O.; Wilcox, M.; Kuijper, E.J. European Society of Clinical Microbiology and Infectious Diseases: Update of the diagnostic guidance document for Clostridium difficile infection. Clin. Microbiol. Infect. 2016, 22, S63–S81. [Google Scholar] [CrossRef] [Green Version]
- Di Bella, S.; Ascenzi, P.; Siarakas, S.; Petrosillo, N.; di Masi, A. Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects. Toxins (Basel) 2016, 8, 134. [Google Scholar] [CrossRef] [Green Version]
- Sethi, A.K.; Al-Nassir, W.N.; Nerandzic, M.M.; Bobulsky, G.S.; Donskey, C.J. Persistence of Skin Contamination and Environmental Shedding ofClostridium difficileduring and after Treatment of C.difficileInfection. Infect. Control. Hosp. Epidemiol. 2010, 31, 21–27. [Google Scholar] [CrossRef] [Green Version]
- Zou, J.; Leung, V.; Champagne, S.; Hinch, M.; Wong, A.; Lloyd-Smith, E.; Nguyen, T.T.; Romney, M.G.; Sharma, A.; Payne, M.; et al. Clinical heterogeneity of patients with stool samples testing PCR+/Tox− from a two-step Clostridium difficile diagnostic algorithm. Eur. J. Clin. Microbiol. Infect. Dis. 2018, 37, 2355–2359. [Google Scholar] [CrossRef] [PubMed]
- Polage, C.R.; Gyorke, C.E.; Kennedy, M.A.; Leslie, J.L.; Chin, D.L.; Wang, S.; Nguyen, H.H.; Huang, B.; Tang, Y.-W.; Lee, L.W.; et al. Overdiagnosis ofClostridium difficileInfection in the Molecular Test Era. JAMA Intern. Med. 2015, 175, 1792–1801. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beaulieu, C.; Dionne, L.-L.; Julien, A.-S.; Longtin, Y. Clinical characteristics and outcome of patients with Clostridium difficile infection diagnosed by PCR versus a three-step algorithm. Clin. Microbiol. Infect. 2014, 20, 1067–1073. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longtin, Y.; Trottier, S.; Brochu, G.; Paquet-Bolduc, B.; Garenc, C.; Loungnarath, V.; Beaulieu, C.; Goulet, D.; Longtin, J. Impact of the Type of Diagnostic Assay on Clostridium difficile Infection and Complication Rates in a Mandatory Reporting Program. Clin. Infect. Dis. 2012, 56, 67–73. [Google Scholar] [CrossRef] [Green Version]
- Planche, T.D.; Davies, K.A.; Coen, P.G.; Finney, J.M.; Monahan, I.M.; Morris, K.A.; O’Connor, L.; Oakley, S.J.; Pope, C.F.; Wren, M.W.; et al. Differences in outcome according to Clostridium difficile testing method: A prospective multicentre diagnostic validation study of C difficile infection. Lancet Infect. Dis. 2013, 13, 936–945. [Google Scholar] [CrossRef] [Green Version]
- Davies, K.; Planche, T.; Wilcox, M.H. The predictive value of quantitative nucleic acid amplification detection of Clostridium difficile toxin gene for faecal sample toxin status and patient outcome. PLoS ONE 2018, 13, e0205941. [Google Scholar] [CrossRef] [Green Version]
- Pollock, N.R.; Banz, A.; Chen, X.; Williams, D.; Xu, H.; Cuddemi, C.A.; Cui, A.X.; Perrotta, M.; Alhassan, E.; Riou, B.; et al. Comparison of Clostridioides difficile Stool Toxin Concentrations in Adults With Symptomatic Infection and Asymptomatic Carriage Using an Ultrasensitive Quantitative Immunoassay. Clin. Infect. Dis. 2018, 68, 78–86. [Google Scholar] [CrossRef]
- Guerrero, D.M.; Chou, C.; Jury, L.A.; Nerandzic, M.M.; Cadnum, J.C.; Donskey, C.J. Clinical and Infection Control Implications of Clostridium difficile Infection With Negative Enzyme Immunoassay for Toxin. Clin. Infect. Dis. 2011, 53, 287–290. [Google Scholar] [CrossRef] [Green Version]
- Davies, K.G.; Longshaw, C.M.; Davis, G.L.; Bouza, E.; Barbut, F.; Barna, Z.; Delmée, M.; Fitzpatrick, F.; Ivanova, K.; Kuijper, E.; et al. Underdiagnosis of Clostridium difficile across Europe: The European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect. Dis. 2014, 14, 1208–1219. [Google Scholar] [CrossRef]
- Alcalá, L.; Martin, A.; Marin, M.; Sánchez-Somolinos, M.; Catalán, P.; Peláez, T.; Bouza, E. The undiagnosed cases of Clostridium difficile infection in a whole nation: Where is the problem? Clin. Microbiol. Infect. 2012, 18, E204–E213. [Google Scholar] [CrossRef] [Green Version]
- Khanna, S.; Pardi, D.S.; Aronson, S.L.; Kammer, P.P.; Orenstein, R.; Sauver, J.L.S.; Harmsen, W.S.; Zinsmeister, A.R. The Epidemiology of Community-Acquired Clostridium difficile Infection: A Population-Based Study. Am. J. Gastroenterol. 2012, 107, 89–95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kotila, S.M.; Mentula, S.; Ollgren, J.; Virolainen-Julkunen, A.; Lyytikäinen, O. Community- and Healthcare-AssociatedClostridium difficileInfections, Finland, 2008−2013. Emerg. Infect. Dis. 2016, 22, 1747–1753. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chitnis, A.S.; Holzbauer, S.M.; Belflower, R.M.; Winston, L.G.; Bamberg, W.M.; Lyons, C.; Farley, M.M.; Dumyati, G.K.; Wilson, L.E.; Beldavs, Z.G.; et al. Epidemiology of Community-AssociatedClostridium difficileInfection, 2009 Through 2011. JAMA Intern. Med. 2013, 173, 1359–1367. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hensgens, M.P.M.; Dekkers, O.M.; Demeulemeester, A.; Buiting, A.G.M.; Bloembergen, P.; Van Benthem, B.; Le Cessie, S.; Kuijper, E.J. Diarrhoea in general practice: When should a Clostridium difficile infection be considered? Results of a nested case-control study. Clin. Microbiol. Infect. 2014, 20, O1067–O1074. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bauer, M.P.; Veenendaal, D.; Verhoef, L.; Bloembergen, P.; Van Dissel, J.; Kuijper, E.J. Clinical and microbiological characteristics of community-onset Clostridium difficile infection in The Netherlands. Clin. Microbiol. Infect. 2009, 15, 1087–1092. [Google Scholar] [CrossRef] [Green Version]
- Wilcox, M.H.; Mooney, L.; Bendall, R.; Settle, C.D.; Fawley, W.N. A case-control study of community-associated Clostridium difficile infection. J. Antimicrob. Chemother. 2008, 62, 388–396. [Google Scholar] [CrossRef] [Green Version]
- Barbut, F.; Day, N.; Bouée, S.; Youssouf, A.; Grandvoinnet, L.; Lalande, V.; Couturier, J.; Eckert, C. Toxigenic Clostridium difficile carriage in general practice: Results of a laboratory-based cohort study. Clin. Microbiol. Infect. 2019, 25, 588–594. [Google Scholar] [CrossRef]
- Debast, S.; Bauer, M.; Kuijper, E.J. European Society of Clinical Microbiology and Infectious Diseases: Update of the Treatment Guidance Document for Clostridium difficile Infection. Clin. Microbiol. Infect. 2014, 20, 1–26. [Google Scholar] [CrossRef] [Green Version]
- Cornely, O.A.; Crook, D.W.; Esposito, R.; Poirier, A.; Somero, M.S.; Weiss, K.; Sears, P.; Gorbach, S.L. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: A double-blind, non-inferiority, randomised controlled trial. Lancet Infect. Dis. 2012, 12, 281–289. [Google Scholar] [CrossRef]
- Louie, T.J.; Miller, M.A.; Mullane, K.M.; Weiss, K.; Lentnek, A.; Golan, Y.; Gorbach, S.; Sears, P.; Shue, Y.-K. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N. Engl. J. Med. 2011, 364, 422–431. [Google Scholar] [CrossRef] [Green Version]
- Bauer, M.P.; Hensgens, M.P.M.; Miller, M.A.; Gerding, D.N.; Wilcox, M.H.; Dale, A.P.; Fawley, W.N.; Kuijper, E.J.; Gorbach, S.L. Renal Failure and Leukocytosis Are Predictors of a Complicated Course of Clostridium difficile Infection if Measured on Day of Diagnosis. Clin. Infect. Dis. 2012, 55, S149–S153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miller, M.A.; Louie, T.; Mullane, K.M.; Weiss, K.; Lentnek, A.; Golan, Y.; Kean, Y.; Sears, P. Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect. Dis. 2013, 13, 148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lungulescu, O.; Cao, W.; Gatskevich, E.; Tlhabano, L.; Stratidis, J. CSI: A severity index for Clostridium difficile infection at the time of admission. J. Hosp. Infect. 2011, 79, 151–154. [Google Scholar] [CrossRef] [PubMed]
- Abou Chakra, C.N.; Pepin, J.; Valiquette, L. Prediction tools for unfavourable outcomes in Clostridium difficile infection: A systematic review. PLoS ONE 2012, 7, e30258. [Google Scholar] [CrossRef] [Green Version]
- Wang, M.S.; Evans, C.T.; Rodriguez, T.; Gerding, D.N.; Johnson, S. Clostridium difficileInfection and Limitations of Markers for Severity in Patients with Hematologic Malignancy. Infect. Control. Hosp. Epidemiol. 2013, 34, 127–132. [Google Scholar] [CrossRef]
- Shah, D.; Bhatt, N.; Welch, J.; Koo, H.; Garey, K.W. Defining acute renal dysfunction as a criterion for the severity of Clostridium difficile infection in patients with community-onset vs hospital-onset infection. J. Hosp. Infect. 2013, 83, 294–299. [Google Scholar] [CrossRef] [Green Version]
- Carignan, A.; Poulin, S.; Martin, P.; Labbé, A.-C.; Valiquette, L.; Al-Bachari, H.; Montpetit, L.-P.; Pépin, J. Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections. Am. J. Gastroenterol. 2016, 111, 1834–1840. [Google Scholar] [CrossRef]
- Guery, B.; Menichetti, F.; Anttila, V.-J.; Adomakoh, N.; Aguado, J.M.; Bisnauthsing, K.; Georgopali, A.; Goldenberg, S.D.; Karas, A.; Kazeem, G.; et al. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): A randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect. Dis. 2018, 18, 296–307. [Google Scholar] [CrossRef] [Green Version]
- Johnson, S.; Louie, T.J.; Gerding, D.N.; Cornely, O.A.; Chasan-Taber, S.; Fitts, D.; Gelone, S.P.; Broom, C.; Davidson, D.M. Polymer Alternative for CDI Treatment (PACT) investigators Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results From Two Multinational, Randomized, Controlled Trials. Clin. Infect. Dis. 2014, 59, 345–354. [Google Scholar] [CrossRef] [Green Version]
- Teasley, D.; Olson, M.; Gebhard, R.; Gerding, D.; Peterson, L.; Schwartz, M.; Lee, J. Prospective Randomised trial of metronidazole versus vancomycin for clostridium-difficile-associated Diarrhoea and colitis. Lancet 1983, 322, 1043–1046. [Google Scholar] [CrossRef]
- Wenisch, C.; Parschalk, B.; Hasenhündl, M.; Hirschl, A.M.; Graninger, W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin. Infect. Dis. 1996, 22, 813–818. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zar, F.A.; Bakkanagari, S.R.; Moorthi, K.M.; Davis, M.B. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin. Infect. Dis. 2007, 45, 302–307. [Google Scholar] [CrossRef] [PubMed]
- Apisarnthanarak, A.; Razavi, B.; Mundy, L.M. Adjunctive Intracolonic Vancomycin for SevereClostridium difficileColitis: Case Series and Review of the Literature. Clin. Infect. Dis. 2002, 35, 690–696. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malamood, M.; Nellis, E.; Ehrlich, A.C.; Friedenberg, F.K. Vancomycin Enemas as Adjunctive Therapy for Clostridium difficile Infection. J. Clin. Med. Res. 2015, 7, 422–427. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rokas, K.E.; Johnson, J.W.; Beardsley, J.R.; Ohl, C.A.; Luther, V.P.; Williamson, J.C. The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated with Improved Mortality in Critically Ill Patients with Clostridium difficile Infection. Clin. Infect. Dis. 2015, 61, 934–941. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bishop, E.J.; Tiruvoipati, R.; Metcalfe, J.; Marshall, C.; Botha, J.; Kelley, P.G. The outcome of patients with severe and severe-complicated Clostridium difficile infection treated with tigecycline combination therapy: A retrospective observational study. Intern. Med. J. 2018, 48, 651–660. [Google Scholar] [CrossRef] [PubMed]
- Britt, N.S.; Steed, M.E.; Potter, E.M.; Clough, L.A. Tigecycline for the Treatment of Severe and Severe Complicated Clostridium difficile Infection. Infect. Dis. Ther. 2014, 3, 321–331. [Google Scholar] [CrossRef] [Green Version]
- Kechagias, K.S.; Chorepsima, S.; Triarides, N.A.; Falagas, M.E. Tigecycline for the treatment of patients with Clostridium difficile infection: An update of the clinical evidence. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 1053–1058. [Google Scholar] [CrossRef]
- McPherson, S.; Rees, C.J.; Ellis, R.; Soo, S.; Panter, S.J. Intravenous Immunoglobulin for the Treatment of Severe, Refractory, and Recurrent Clostridium difficile Diarrhea. Dis. Colon Rectum 2006, 49, 640–645. [Google Scholar] [CrossRef]
- Cornely, O.A.; Miller, M.A.; Louie, T.J.; Crook, D.W.; Gorbach, S.L. Treatment of first recurrence of Clostridium difficile infection: Fidaxomicin versus vancomycin. Clin. Infect. Dis. 2012, 55 (Suppl. S2), S154–S161. [Google Scholar] [CrossRef]
- Spiceland, C.M.; Khanna, S.; Pardi, D.S. Outcomes with Fidaxomicin Therapy in Clostridium difficile Infection. J. Clin. Gastroenterol. 2018, 52, 151–154. [Google Scholar] [CrossRef] [PubMed]
- McFarland, L.V.; Elmer, G.W.; Surawicz, C.M. Breaking the cycle: Treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am. J. Gastroenterol. 2002, 97, 1769–1775. [Google Scholar] [CrossRef] [PubMed]
- Van Nood, E.; Vrieze, A.; Nieuwdorp, M.; Fuentes, S.; Zoetendal, E.G.; de Vos, W.M.; Visser, C.E.; Kuijper, E.J.; Bartelsman, J.F.; Tijssen, J.G.; et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 2013, 368, 407–415. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longo, W.E.; Mazuski, J.E.; Virgo, K.S.; Lee, P.; Bahadursingh, A.N.; Johnson, F.E. Outcome after colectomy for Clostridium difficile colitis. Dis. Colon Rectum 2004, 47, 1620–1626. [Google Scholar] [CrossRef] [PubMed]
- Kelly, C.P. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin. Microbiol. Infect. 2012, 18, 21–27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lamontagne, F.; Labbé, A.-C.; Haeck, O.; Lesur, O.; Lalancette, M.; Patino, C.; Leblanc, M.; Laverdière, M.; Pépin, J. Impact of Emergency Colectomy on Survival of Patients With Fulminant Clostridium difficile Colitis During an Epidemic Caused by a Hypervirulent Strain. Ann. Surg. 2007, 245, 267–272. [Google Scholar] [CrossRef] [PubMed]
- Miller, A.T.; Tabrizian, P.; Greenstein, A.J.; Dikman, A.; Byrn, J.; Divino, C.M. Long-Term Follow-Up of Patients with Fulminant Clostridium difficile Colitis. J. Gastrointest. Surg. 2009, 13, 956–959. [Google Scholar] [CrossRef]
- Neal, M.D.; Alverdy, J.C.; Hall, D.E.; Simmons, R.L.; Zuckerbraun, B.S. Diverting loop ileostomy and colonic lavage: An alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann. Surg. 2011, 254, 423–427. [Google Scholar] [CrossRef]
- Juo, Y.-Y.; Sanaiha, Y.; Jabaji, Z.; Benharash, P. Trends in Diverting Loop Ileostomy vs Total Abdominal Colectomy as Surgical Management for Clostridium difficile Colitis. JAMA Surg. 2019, 154, 899–906. [Google Scholar] [CrossRef]
- Lowy, I.; Molrine, D.C.; Leav, B.A.; Blair, B.M.; Baxter, R.; Gerding, D.N.; Nichol, G.; Thomas, W.D.; Leney, M.; Sloan, S.; et al. Treatment with Monoclonal Antibodies againstClostridium difficileToxins. N. Engl. J. Med. 2010, 362, 197–205. [Google Scholar] [CrossRef] [Green Version]
- Wilcox, M.H.; Gerding, D.N.; Poxton, I.R.; Kelly, C.; Nathan, R.; Birch, T.; Cornely, O.A.; Rahav, G.; Bouza, E.; Lee, C.; et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N. Engl. J. Med. 2017, 376, 305–317. [Google Scholar] [CrossRef] [PubMed]
- Nathwani, D.; Cornely, O.A.; Van Engen, A.K.; Odufowora-Sita, O.; Retsa, P.; Odeyemi, I.A.O. Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection. J. Antimicrob. Chemother. 2014, 69, 2901–2912. [Google Scholar] [CrossRef] [PubMed]
- Prabhu, V.S.; Dubberke, E.R.; Dorr, M.B.; Elbasha, E.; Cossrow, N.; Jiang, Y.; Marcella, S. Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection. Clin. Infect. Dis. 2018, 66, 355–362. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Salavert, M.; Cobo, J.; Pascual, Á.; Aragón, B.; Maratia, S.; Jiang, Y.; Aceituno, S.; Grau, S. Cost-Effectiveness Analysis of Bezlotoxumab Added to Standard of Care Versus Standard of Care Alone for the Prevention of Recurrent Clostridium difficile Infection in High-Risk Patients in Spain. Adv. Ther. 2018, 35, 1920–1934. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gerding, D.N.; Kelly, C.P.; Rahav, G.; Lee, C.; Dubberke, E.R.; Kumar, P.N.; Yacyshyn, B.; Kao, D.; Eves, K.; Ellison, M.C.; et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin. Infect. Dis. 2018, 67, 649–656. [Google Scholar] [CrossRef]
- Oksi, J.; Aalto, A.; Säilä, P.; Partanen, T.; Anttila, V.-J.; Mattila, E. Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: A retrospective study of 46 patients in five university hospitals in Finland. Eur. J. Clin. Microbiol. Infect. Dis. 2019, 38, 1947–1952. [Google Scholar] [CrossRef] [Green Version]
- Cammarota, G.; Masucci, L.; Ianiro, G.; Bibbo, S.; Dinoi, G.; Costamagna, G.; Sanguinetti, M.; Gasbarrini, A. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment. Pharmacol. Ther. 2015, 41, 835–843. [Google Scholar] [CrossRef]
- Furuya-Kanamori, L.; Doi, S.A.; Paterson, D.L.; Helms, S.K.; Yakob, L.; McKenzie, S.J.; Garborg, K.; Emanuelsson, F.; Stollman, N.; Kronman, M.P.; et al. Upper Versus Lower Gastrointestinal Delivery for Transplantation of Fecal Microbiota in Recurrent or Refractory Clostridium difficile Infection: A Collaborative Analysis of Individual Patient Data From 14 Studies. J. Clin. Gastroenterol. 2017, 51, 145–150. [Google Scholar] [CrossRef]
- Lee, C.H.; Steiner, T.; Petrof, E.O.; Smieja, M.; Roscoe, D.; Nematallah, A.; Weese, J.S.; Collins, S.; Moayyedi, P.; Crowther, M.; et al. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients with Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA 2016, 315, 142–149. [Google Scholar] [CrossRef] [Green Version]
- Tang, G.; Yin, W.; Liu, W. Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection: A meta-analysis? Diagn. Microbiol. Infect. Dis. 2017, 88, 322–329. [Google Scholar] [CrossRef]
- Youngster, I.; Mahabamunuge, J.; Systrom, H.K.; Sauk, J.; Khalili, H.; Levin, J.; Kaplan, J.L.; Hohmann, E.L. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med. 2016, 14, 1–4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Youngster, I.; Russell, G.H.; Pindar, C.; Ziv-Baran, T.; Sauk, J.; Hohmann, E.L. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for RelapsingClostridium difficileInfection. JAMA 2014, 312, 1772–1778. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kao, D.; Roach, B.; Silva, M.; Beck, P.; Rioux, K.; Kaplan, G.G.; Chang, H.-J.; Coward, S.; Goodman, K.J.; Xu, H.; et al. Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA 2017, 318, 1985–1993. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Staley, C.; Hamilton, M.J.; Vaughn, B.P.; Graiziger, C.T.; Newman, K.M.; Kabage, A.J.; Sadowsky, M.J.; Khoruts, A. Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study. Am. J. Gastroenterol. 2017, 112, 940–947. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, Z.D.; Ajami, N.J.; Petrosino, J.F.; Jun, G.; Hanis, C.L.; Shah, M.; Hochman, L.; Ankoma-Sey, V.; Dupont, A.W.; Wong, M.C.; et al. Randomised clinical trial: Faecal microbiota transplantation for recurrent Clostridum difficile infection-fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy. Aliment. Pharmacol. Ther. 2017, 45, 899–908. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cammarota, G.; Ianiro, G.; Tilg, H.; Rajilić-Stojanović, M.; Kump, P.; Satokari, R.; Sokol, H.; Arkkila, P.; Pintus, C.; Hart, A.; et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut 2017, 66, 569–580. [Google Scholar] [CrossRef]
- Seekatz, A.M.; Aas, J.; Gessert, C.E.; Rubin, T.A.; Saman, D.M.; Bakken, J.S.; Young, V.B. Recovery of the Gut Microbiome following Fecal Microbiota Transplantation. mBio 2014, 5, e00893-14. [Google Scholar] [CrossRef] [Green Version]
- Ott, S.J.; Waetzig, G.H.; Rehman, A.; Moltzau-Anderson, J.; Bharti, R.; Grasis, J.A.; Cassidy, L.; Tholey, A.; Fickenscher, H.; Seegert, D.; et al. Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection. Gastroenterol. 2017, 152, 799–811. [Google Scholar] [CrossRef] [Green Version]
- Young, V.B. The role of the microbiome in human health and disease: An introduction for clinicians. BMJ 2017, 356, j831. [Google Scholar] [CrossRef]
- Lee, C.H.; Belanger, J.E.; Kassam, Z.; Smieja, M.; Higgins, D.; Broukhanski, G.; Kim, P.T. The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur. J. Clin. Microbiol. Infect. Dis. 2014, 33, 1425–1428. [Google Scholar] [CrossRef]
- Lee, C.H.; Chai, J.; Hammond, K.; Jeon, S.R.; Patel, Y.; Goldeh, C.; Kim, P. Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure. Eur. J. Clin. Microbiol. Infect. Dis. 2019, 38, 1731–1735. [Google Scholar] [CrossRef] [PubMed]
- Van Hise, N.W.; Bryant, A.M.; Hennessey, E.K.; Crannage, A.J.; Khoury, J.A.; Manian, F.A. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated with Systemic Antimicrobial Agents. Clin. Infect. Dis. 2016, 63, 651–653. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Curry, S.R.; Muto, C.A.; Schlackman, J.L.; Pasculle, A.W.; Shutt, K.A.; Marsh, J.W.; Harrison, L.H. Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin. Infect. Dis. 2013, 57, 1094–1102. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loo, V.G.; Bourgault, A.-M.; Poirier, L.; Lamothe, F.; Michaud, S.; Turgeon, N.; Toye, B.; Beaudoin, A.; Frost, E.H.; Gilca, R.; et al. Host and Pathogen Factors forClostridium difficileInfection and Colonization. N. Engl. J. Med. 2011, 365, 1693–1703. [Google Scholar] [CrossRef] [Green Version]
- Galdys, A.L.; Curry, S.R.; Harrison, L.H. Asymptomatic Clostridium difficile colonization as a reservoir for Clostridium difficile infection. Expert Rev. Anti-Infect. Ther. 2014, 12, 967–980. [Google Scholar] [CrossRef]
- Guerrero, D.; Becker, J.; Eckstein, E.; Kundrapu, S.; Deshpande, A.; Sethi, A.; Donskey, C. Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized patients. J. Hosp. Infect. 2013, 85, 155–158. [Google Scholar] [CrossRef]
- Johnson, S.; Clabots, C.; Linn, F.; Olson, M.; Peterson, L.; Gerding, D. Nosocomial Clostridium difficile colonisation and disease. Lancet 1990, 336, 97–100. [Google Scholar] [CrossRef]
- Lanzas, C.; Dubberke, E.R.; Lu, Z.; Reske, K.A.; Gröhn, Y.T. Epidemiological Model forClostridium difficileTransmission in Healthcare Settings. Infect. Control. Hosp. Epidemiol. 2011, 32, 553–561. [Google Scholar] [CrossRef] [Green Version]
- Riggs, M.M.; Sethi, A.K.; Zabarsky, T.F.; Eckstein, E.C.; Jump, R.L.P.; Donskey, C.J. Asymptomatic Carriers Are a Potential Source for Transmission of Epidemic and Nonepidemic Clostridium difficile Strains among Long-Term Care Facility Residents. Clin. Infect. Dis. 2007, 45, 992–998. [Google Scholar] [CrossRef]
- Gilboa, M.; Houri-Levi, E.; Cohen, C.; Tal, I.; Rubin, C.; Feld-Simon, O.; Brom, A.; Eden-Friedman, Y.; Segal, S.; Rahav, G.; et al. Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study. Clin. Microbiol. Infect. 2020, 26, 1052–1057. [Google Scholar] [CrossRef]
- Kyne, L.; Warny, M.; Qamar, A.; Kelly, C.P. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N. Engl. J. Med. 2000, 342, 390–397. [Google Scholar] [CrossRef] [PubMed]
- Kyne, L.; Warny, M.; Qamar, A.; Kelly, C.P. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 2001, 357, 189–193. [Google Scholar] [CrossRef]
- Shim, J.K.; Johnson, S.; Samore, M.H.; Bliss, D.Z.; Gerding, D.N. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet 1998, 351, 633–636. [Google Scholar] [CrossRef]
- Gerding, D.N.; Meyer, T.; Lee, C.; Cohen, S.H.; Murthy, U.K.; Poirier, A.; Van Schooneveld, T.C.; Pardi, D.S.; Ramos, A.; Barron, M.A.; et al. Administration of Spores of NontoxigenicClostridium difficileStrain M3 for Prevention of RecurrentC difficileInfection. JAMA 2015, 313, 1719–1727. [Google Scholar] [CrossRef] [Green Version]
- Zacharioudakis, I.M.; Zervou, F.N.; Pliakos, E.E.; Ziakas, P.D.; Mylonakis, E. Colonization With Toxinogenic, C. difficile Upon Hospital Admission, and Risk of Infection: A Systematic Review and Meta-Analysis. Am. J. Gastroenterol. 2015, 110, 381–390. [Google Scholar] [CrossRef]
- Longtin, Y.; Paquet-Bolduc, B.; Gilca, R.; Garenc, C.; Fortin, E.; Longtin, J.; Trottier, S.; Gervais, P.; Roussy, J.-F.; Lévesque, S.; et al. Effect of Detecting and Isolating Clostridium difficile Carriers at Hospital Admission on the Incidence of C difficile Infections: A Quasi-Experimental Controlled Study. JAMA Intern. Med. 2016, 176, 796–804. [Google Scholar] [CrossRef] [Green Version]
Patient characteristics | Age > 65 years old Immunosuppression | Laboratory findings | Leucocytes > 15,000 cells/mL Creatinine > 133 μmol/L |
Physical examination | Fever > 38.5 °C Rigors Peritonitis Ileus Respiratory failure (mechanical ventilation) Hemodynamic instability | Left shift (bands > 20%) Albumine < 30 g/L Lactates > 5 mmol/L | |
Imaging | Distension of large intestine > 6 cm Colonic wall thickening Pericolonic fat stranding Ascites (not explained by other causes) | ||
Endoscopy | Pseudomembranous colitis |
Study | TrT | Number of Patients | CC (%) | CC (%) | Rec (%) | ||
---|---|---|---|---|---|---|---|
Global | Mild | Mod | Sev | ||||
Johnson [49] | MTZ | 278 | 72.7 | 78.7 | 73.9 | 66.3 | 23 |
VCM | 259 | 81.1 * | 82.7 | 82.2 | 78.5 * | 20.6 * | |
Teasley [50] | MTZ | 42 | 88 | 2.7 | |||
VCM | 52 | 86 | 13.3 | ||||
Wenisch [51] | MTZ | 31 | 94 | 16 | |||
VCM | 31 | 94 | 16 | ||||
Zar [52] | MTZ | 79 | 84 | 90 | 76 | 14 | |
VCM | 71 | 97 | 98 | 97 * | 7 | ||
Louie [40] | VCM | 309 | 85.8 | 85 | 83 | 88.6 | 25.3 |
FDX | 287 | 88.2 | 92.2 | 91.9 | 82.1 | 15.4 * | |
Cornely [39] | VCM | 257 | 86.8 | 91.5 | 76.2 | 26.9 | |
FDX | 252 | 87.7 | 91.7 | 73.4 | 12.7 * | ||
Guery [48] | VCM | 179 | 82 | 19 | |||
EPFDX | 177 | 78 | 6 * |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kampouri, E.; Croxatto, A.; Prod’hom, G.; Guery, B. Clostridioides difficile Infection, Still a Long Way to Go. J. Clin. Med. 2021, 10, 389. https://doi.org/10.3390/jcm10030389
Kampouri E, Croxatto A, Prod’hom G, Guery B. Clostridioides difficile Infection, Still a Long Way to Go. Journal of Clinical Medicine. 2021; 10(3):389. https://doi.org/10.3390/jcm10030389
Chicago/Turabian StyleKampouri, Eleftheria, Antony Croxatto, Guy Prod’hom, and Benoit Guery. 2021. "Clostridioides difficile Infection, Still a Long Way to Go" Journal of Clinical Medicine 10, no. 3: 389. https://doi.org/10.3390/jcm10030389