• Users Online: 207
  • Print this page
  • Email this page


 
 
Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 17  |  Issue : 4  |  Page : 323-326

Clostridium Difficile-associated diarrhea: A mini-review


1 Department of Microbiology, College of Medicine, University of Babylon, Hilla, Iraq
2 Department of Medical Lab Technology, Shatrah Technical College, Southern Technical University, Thi-Qar, Iraq

Date of Submission20-Sep-2020
Date of Acceptance01-Oct-2020
Date of Web Publication14-Dec-2020

Correspondence Address:
Inas Ahmed Saeed
Department of Microbiology, College of Medicine, University of Babylon, Hilla
Iraq
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/MJBL.MJBL_65_20

Get Permissions

  Abstract 


The most common cause of antibiotic-associated diarrhea in hospitals and other health-care facilities is Clostridium difficile which is also cause of significant concern because of the increasing morbidity and mortality rates as well as increased health-care costs. The infection by this bacterium was ranging from mild, self-limiting diarrhea to serious diarrhea, pseudomembranous colitis, and life-threatening fulminant colitis which may lead to death. Infection by C. difficile develops after ingestion spores of this toxigenic strain by the patients through personal contact or environment. Pathogenicity depending on the production of two types of enterotoxins by bacteria: Tcd A and Tcd B toxins responsible for fluid secretion, inflammation, and tissue necrosis, so identification of this bacterium is depending on the presence of an important virulence factor (enterotoxin) in the stool by using tissue culture cytotoxicity assay, or by enzyme immunoassay for C. difficile glutamate dehydrogenase antigen, and sometimes by endoscopy to verify pseudomembranous colitis. The infection can be effectively treated by metronidazole and vancomycin before that, fluids, and electrolytes replacement must be supplied.

Keywords: Clostridium difficile, diarrhea, enterotoxins


How to cite this article:
Saeed IA, Al-Zaidi JR. Clostridium Difficile-associated diarrhea: A mini-review. Med J Babylon 2020;17:323-6

How to cite this URL:
Saeed IA, Al-Zaidi JR. Clostridium Difficile-associated diarrhea: A mini-review. Med J Babylon [serial online] 2020 [cited 2021 Jun 13];17:323-6. Available from: https://www.medjbabylon.org/text.asp?2020/17/4/323/303261




  Introduction Top


Clostridia are an important cause of morbidity and mortality in humans and animals. Some of the most common clostridial infections are those of the gut. The primary infections in humans are Clostridium perfringens food poisoning and C. difficile-mediated antibiotic-associated diarrhea and colitis.[1]

C. difficile is a Gram-positive, strictly anaerobic, and spore-forming bacteria. In 1935, it was firstly isolated from feces and meconium of asymptomatic newborn infants. Due to its morphology and encountered the difficulties in cultivating it, it was named Bacillus difficile. Approximately 10%–35% of all cases of antibiotic-associated diarrhea and the most common infectious cause of nosocomial diarrhea which is associated with substantial morbidity and mortality attributed to infection by these bacteria,[2] for example, in the United State, the disease has an estimated annual cost of $ 3.2 billion.[3] The infection of C. difficile is mainly a healthcare associated illness (80%) whereas community-acquired C. difficile infection (CDI) (20%) is also of concern.


  Pathogenesis Top


After ingestion the spores of a toxigenic strains of C. difficile by patient through personal contact or environment, the infection by these bacteria develops whereas C. difficile does not problems among healthy people due to in part commensal bowel flora and antibody-mediated immunity. In the setting of an abnormal or disrupted colonic mucosa, spores of these bacteria colonize the bowel and subsequently germinate to form vegetative bacterial cells which starting to produce two large toxins: An enterotoxin TcdA and a cytotoxin, TcdB. The two toxins are encoded by tcdA and tcdB genes, respectively. Enterotoxin TcdA primarily acts on intestinal epithelium, leading to cause fluid secretion, inflammation and tissue necrosis, whereas the other one TcdB with its broad cell tropism acts as a potent cytotoxin.[4] Some strains of Clostridium known as NAP1/BI/027 characterized by containing an additional virulence factor (binary toxin) expressed from the cdtA (enzymatic component) and cdtB (binding component) operon. Until now, it is unknown the extent to which this toxin contributes to the pathogenecity of C. Difficile; however, these bacteria were first detected caused severe pseudomembranous colitis, there is no correlation between the severity of disease and the level of fecal toxin [Figure 1].[5]
Figure 1: Pathogenesis of Clostridium difficile infection[6]

Click here to view



  Epidemiology Top


C. difficile is the causative agent of approximately 10%–35% of all cases of antibiotic-associated diarrhea and the most common infectious cause of nosocomial diarrhea, which is associated with substantial morbidity and mortality rates as well as increased health-care costs.[3]

There is an increasing in the incidence and severity of the disease as the data from different area of the world: Canada, Europe, and the United states disclosed.[7],[8] There are multiple factors responsible for increasing the incidence and severity of the disease including changing demographic situation, increased use of broad-spectrum antibiotics and emergence of hypervirulent C. difficile strains known as NAP1/BI/027.[9],[10] This strain is characterized by increased production of toxin A and B, the presence of an additional potential virulence factor (binary toxin) and resistance to newer fluoroquinolone antibiotics, such as moxifloxacin[11] so this strain was not reported outside Europe and North America, since the late 1990 until 2007, but a survey of period 2008–2010 showed global spread had occurred[12] as a result of movement of people, animals, vectors, and inanimate objects across international borders.[10] In different studies, the incidence of CDI varies widely according to the type of hospital care (acute care, long-term) patient population (elderly, young) and the presence or absence of nosocomial outbreaks. For example, prolonged hospitalization and increased number of elderly patients (patients older than 65 years) explain why the incidence of CDI is increased in long-term hospitals. Other study showed that prevalence of C. difficile was significantly higher in hospitalized patients versus community patients (P = 0.0227).[13]


  Clinical Features Top


A symptomatic carriers vary from 2% in the community to 20%–30% or more in hospitalized adults.[14] Although asymptomatic, these individuals serves as reservoir for environmental contamination.[15] The period of incubation between ingestion spore and onset of disease has not be determined. However, most patients develop diarrhea during or shortly after taking antibiotics or up to 8–10 weeks after its decontamination.[15],[16] The infection by C. difficile has a wide spectrum range of clinical presentations from mild, self-limiting diarrhea, to serious diarrhea, pseudomembranous colitis, and life-threatening fulminant colitis, which may leading to death. The most important symptom of CDI is watery diarrhea[17] which is varies from mild, moderate to severe. Patients with colitis (with or without pseudomembransss) usually present with watery diarrhea up to 10–15 times daily, abdominal cramping and pain, fever, anorexia, and nausea so a leukemoid reaction, hypoalbuminemia and occult colonic bleeding may occur, but visible blood is rare.[18]


  Diagnosis Top


The diagnosis of CDI is basically depend on the clinical features confirmation of the presence of either toxin A alone or both toxins (A and B) together in the stool, and sometimes endoscopy to be sure of pseudomembranous colitis. For those hospitalized patients, who develops diarrhea or any person in the community who develops diarrhea, infection by C. difficile should be suspected especially after a course of antibiotics or in association with immunosuppressive therapy. The prevalence of CDI to be 15% in patients with diarrhea.[13] To confirm infection by C. difficile, diagnostic tests are essential, so testing for the bacteria or their toxins must be done only on diarrheal (unformed) stool unless ileus due to C. difficile is suspected. Bacterial cytotoxin (toxin B) can be detected by tissue culture cytotoxicity assay in stool filtrate, is considered to be the (gold standard) because it can detect as little as 10 pg of toxin in stool and has a high sensitivity (94%–100%) and specificity (99%–100%).[19],[20]

All strains of C. difficile isolates with toxigenic and nontoxigenic are producer to glutamate dehydrogenase (GDH), C. Difficile (GDH) antigen can be detected by enzyme immunoassay (EIA) which is highly sensitive test (75%–90%) and high negative predictive value (95%–100%).[20],[21] Hence, this test is used for detecting presence of toxin A and toxin B of C. difficile in stool. Although this test has reduced sensitivity (65%–85%) it remains the main diagnostic modality and ease of performance because it provides results within (2–6) hours with specificity of (95%–100%).[19],[22] Polymerase chain reaction (PCR) and RT-PCR methods are the diagnostic strategies targeting nucleic acids, they have been developed to detect gene encoding Tcd A and/or Tcd B.[23] There is another highly sensitive laboratory method for anaerobically isolation of C. difficile from stool in culture media, but this method (test) is rarely used for clinical diagnosis because the test required a few days (2–3) to complete and does not differentiate between toxigenic from nontoxigenic strains of these bacteria,[24] however, this test is important and required for epidemiological studies (i.e., for strain typing in outbreaks of nosocomial infection).[25] In special situations, such as when other diseases need to be ruled out, the diagnosis is in doubt or the clinical situation required rapid diagnosis, or it is difficult for obtaining a stool sample because ileus develops therefore, Endoscopy is helpful in).[26],[27] To assist the severity of CDI, radiographic imaging studies can be used, computed tomography-scanning also can help categorize the severity of colitis, and it can diagnose fulminant colitis rapidly, so the ascites, free air, colon wall thickening, or dilation can be shown.[28],[29]


  Treatment Top


To treat a patient with documented or suspected CDI, the first step includes: Stopping the inciting agent such as antimicrobials, if possible, and providing appropriate supportive care with hydration and electrolyte replacement as needed.[25] It should be to avoid anti-diarrheal medications as they may obscure symptoms and precipitate toxic megacolon. The mainstays of antimicrobial therapy for CDI are metronidazole and vancomycin.[14],[30],[31] In the recommended doses, both of metronidazole and vancomycin have similar efficacy with response rate 90%–97%. Resolution of fever and diarrhea on the 4th or 5th day refers to therapeutic response. The following antibiotics: fidaxomicin, bacitracin, teicoplanin, fusidic acid and nitazoxanide, rifaximin and rifampin, may be considered as alternative therapy for CDI in the unusual events (e.g., allergy or intolerance to both first-line agents).[32] There are other methods for treatment such intravenous immunoglobulin, specific monoclonal antibodies therapy and toxin-binding agents,[33] all of them are nonantimicrobial therapies.


  Prevention Top


Prevention is best accomplished by implementation of infection-control measures and by judicious use of antibacterial agents.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hmood AM, Al-Shukri MS, Al-Charrakh AH. Molecular detection and antimicrobial resistance of Clostridium perfringens isolated from diabetic patients and bullet wounds. J App Biol Biotech 2019;7:54-9.  Back to cited text no. 1
    
2.
Ricciardi R, Rothenberger DA, Madoff RD, Baxter NN. Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Arch Surg 2007;142:624-31.  Back to cited text no. 2
    
3.
O'Brien JA, Lahue BJ, Caro JJ, Davidson DM. The emerging infectious challenge of Clostridium difficile-associated disease in Massachusetts hospitals: Clinical and economic consequences. Infect Control Hosp Epidemiol 2007;28:1219-27.  Back to cited text no. 3
    
4.
Rupnik M, Dupuy B, Fairweather NF, Gerding DN, Johnson S, Just I, et al. Revised nomenclature of Clostridium difficile toxins and associated genes. J Med Microbiol 2005;54:113-7.  Back to cited text no. 4
    
5.
Akerlund T, Svenungsson B, Lagergren A, Burman LG. Correlation of disease severity with fecal toxin levels in patients with Clostridium difficile-associated diarrhea and distribution of PCR ribotypes and toxin yields in vitro of corresponding isolates. J Clin Microbiol 2006;44:353-8.  Back to cited text no. 5
    
6.
Elzouki AN, Khan FY. Clostridium difficile infection: A review of the literature. Asian Pac J Trop Med 2014;7:56-13.  Back to cited text no. 6
    
7.
Tillotson GS, Tillotson J. Clostridium difficile-A moving target. F1000 Med Rep 2011;3:6.  Back to cited text no. 7
    
8.
McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353:2433-41.  Back to cited text no. 8
    
9.
Vaishnavi C. Clostridium difficile infection: Clinical spectrum and approach to management. Indian J Gastroenterol 2011;30:245-54.  Back to cited text no. 9
    
10.
Freeman J, Bauer MP, Baines SD, Corver J, Fawley WN, Goorhuis B, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 2010;23:529-49.  Back to cited text no. 10
    
11.
Riley TV. Epidemic Clostridium difficile. Med J Aust 2006;185:133-4.  Back to cited text no. 11
    
12.
Clements AC, Magalhães RJ, Tatem AJ, Paterson DL, Riley TV. Clostridium difficile PCR ribotype 027: Assessing the risks of further worldwide spread. Lancet Infect Dis 2010;10:395-404.  Back to cited text no. 12
    
13.
Curcio D, Cané A, Fernández FA, Correa J. Clostridium difficile-associated diarrhea in developing countries: A systematic review and meta-analysis. Infect Dis Ther 2019;8:87-103.  Back to cited text no. 13
    
14.
Thompson I. Clostridium difficile-associated disease: Update and focus on non-antibiotic strategies. Age Ageing 2008;37:14-8.  Back to cited text no. 14
    
15.
McFarland LV, Surawicz CM, Stamm WE. Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients. J Infect Dis 1990;162:678-84.  Back to cited text no. 15
    
16.
Anand A, Bashey B, Mir T, Glatt AE. Epidemiology, clinical manifestations, and outcome of Clostridium difficile-associated diarrhea. Am J Gastroenterol 1994;89:519-23.  Back to cited text no. 16
    
17.
Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med 1994;330:257-62.  Back to cited text no. 17
    
18.
Wanahita A, Goldsmith EA, Musher DM. Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by Clostridium difficile. Clin Infect Dis 2002;34:1585-92.  Back to cited text no. 18
    
19.
Staneck JL, Weckbach LS, Allen SD, Siders JA, Gilligan PH, Coppitt G, et al. Multicenter evaluation of four methods for Clostridium difficile detection: ImmunoCard C. difficile, cytotoxin assay, culture, and latex agglutination. J Clin Microbiol 1996;34:2718-21.  Back to cited text no. 19
    
20.
Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013;108:478-98.  Back to cited text no. 20
    
21.
Heinlen L, Ballard JD. Clostridium difficile infection. Am J Med Sci 2010;340:247-52.  Back to cited text no. 21
    
22.
Yassin SF, Young-Fadok TM, Zein NN, Pardi DS. Clostridium difficile-associated diarrhea and colitis. Mayo Clin Proc 2001;76:725-30.  Back to cited text no. 22
    
23.
Persson S, Torpdahl M, Olsen KE. New multiplex PCR method for the detection of Clostridium difficile toxin A (tcdA) and toxin B (tcdB) and the binary toxin (cdtA/cdtB) genes applied to a Danish strain collection. Clin Microbiol Infect 2008;14:1057-64.  Back to cited text no. 23
    
24.
Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile-Associated diarrhea: A review. Arch Intern Med 2001;161:525-33.  Back to cited text no. 24
    
25.
Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55.  Back to cited text no. 25
    
26.
Calfee DP. Clostridium difficile: A reemerging pathogen. Geriatrics 2008;63:10-21.  Back to cited text no. 26
    
27.
Johal SS, Hammond J, Solomon K, James PD, Mahida YR. Clostridium difficile associated diarrhoea in hospitalized patients: Onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004;53:673-7.  Back to cited text no. 27
    
28.
Schroeder MS. Clostridium difficile-associated diarrhea. Am Fam Physician 2005;71:921-8.  Back to cited text no. 28
    
29.
Paltansing S, van den Berg RJ, Guseinova RA, Visser CE, van der Vorm ER, Kuijper EJ. Characteristics and incidence of Clostridium difficile-associated disease in The Netherlands, 2005. Clin Microbiol Infect 2007;13:1058-64.  Back to cited text no. 29
    
30.
Cloud J, Kelly CP. Update on Clostridium difficile associated disease. Curr Opin Gastroenterol 2007;23:4-9.  Back to cited text no. 30
    
31.
Drekonja DM, Butler M, MacDonald R, Bliss D, Filice GA, Rector TS, et al. Comparative effectiveness of Clostridium difficile treatments: A systematic review. Ann Intern Med 2011;155:839-47.  Back to cited text no. 31
    
32.
Nelson RL, Kelsey P, Leeman H, Meardon N, Patel H, Paul K, et al. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev 2017;3:CD004610.  Back to cited text no. 32
    
33.
Cheng AC, Ferguson JK, Richards MJ, Robson JM, Gilbert GL, McGregor A, et al. Australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection. Med J Aust 2011;194:353-8.  Back to cited text no. 33
    


    Figures

  [Figure 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Pathogenesis
Epidemiology
Clinical Features
Diagnosis
Treatment
Prevention
References
Article Figures

 Article Access Statistics
    Viewed758    
    Printed32    
    Emailed0    
    PDF Downloaded84    
    Comments [Add]    

Recommend this journal