|Year : 2014 | Volume
| Issue : 4 | Page : 219-222
Clostridium difficile associated diarrhea - 'suspect, inspect, treat, and prevent'
Shivani Tyagi, Aroma Oberoi
Department of Microbiology, Christian Medical College and Hospital, Ludhiana, Punjab, India
|Date of Web Publication||16-Oct-2014|
Dr. Aroma Oberoi
Department of Microbiology, Christian Medical College and Hospital, Ludhiana - 141 008, Punjab
Source of Support: None, Conflict of Interest: None
Context: Clostridium difficile is a fastidious, gram-positive, spore-forming bacterium responsible for infectious diarrhea and pseudomembranous colitis associated with significant morbidity and mortality. Only toxigenic strains produce disease in humans. Pathogenicity is dependent on the presence of diarrhea-producing toxins, named toxin A (TcdA) and toxin B (TcdB). Risk factors include depletion of protective gut flora by antibiotics and diminished immune response to C. difficile due to age and medical co morbidities; and increased use of proton-pump inhibitors (PPI). Treatment includes the stoppage of inciting antibiotics if possible, to allow regeneration of the normal gut microflora, and starting an antibiotic with activity against C. difficile. A good clinical suspicion in patient with co morbidities developing diarrhea during hospital stay can help reduce the burden of this treatable morbid infection. Our aim of doing this study was to determine the prevalence of this infection in our tertiary care hospital, so as to monitor its burden in future. Aims: To determine the prevalence of this infection in our tertiary care hospital. Settings and Design: A retrospective study was conducted in the department of Microbiology in a tertiary care hospital in North India. Materials and Methods: A total of 195 stool samples received over a period of 2 years were included in the study. An enzyme immunoassay was performed for the qualitative determination of toxins A and B from Clostridium difficile in stool samples. Results: A total of 13 (6.67%) stool samples out of 195 samples processed were positive for the presence of Clostridium difficile toxins A/B. Conclusions: CDI has become a global public health challenge today. Various studies show a prevalence rate between 11% - 22%. Lower prevalence rate revealed from our study (6.7%), makes it imperative to maintain a strict surveillance in our patients to ensure opportune detection and treatment
Keywords: Clostridium difficile associated diarrhea, Clostridium difficile infection, pseudomembranous colitis
|How to cite this article:|
Tyagi S, Oberoi A. Clostridium difficile associated diarrhea - 'suspect, inspect, treat, and prevent'. CHRISMED J Health Res 2014;1:219-22
|How to cite this URL:|
Tyagi S, Oberoi A. Clostridium difficile associated diarrhea - 'suspect, inspect, treat, and prevent'. CHRISMED J Health Res [serial online] 2014 [cited 2019 Jan 16];1:219-22. Available from: http://www.cjhr.org/text.asp?2014/1/4/219/142980
| Introduction|| |
Clostridium difficile is a fastidious, gram-positive, spore-forming bacterium responsible for infectious diarrhea and pseudomembranous colitis with significant morbidity and mortality. C. difficile colonizes the large intestine of humans and domestic and wild mammals. Both toxigenic and nontoxigenic strains exist, but only toxigenic forms produce disease in humans. Pathogenicity is dependent on the presence of one or both of two closely related diarrhea-producing toxins, named toxin A (TcdA) and toxin B (TcdB).  Risk factors for C. difficile in these individuals with psedomembranous colitis include depletion of protective gut flora by antibiotics ,, and diminished immune response to C. difficile due to age and medical comorbidities. , The ability of C. difficile to cause enteritis is based upon two host features: colonization resistance and immune response to C. difficile. The large intestine is protected from invasive pathogens by indigenous flora composed of approximately 4,000 bacterial species,  collectively called the fecal microbiome. These microbes collectively provide colonization resistance against pathogenic species through competition for essential nutrients and attachment sites to the gut wall.  Antibiotics disrupt the barrier microflora and diminish colonization resistance, thereby providing a niche for colonization by intestinal pathogens. ,, Virtually every class of antibiotics, apart from the aminoglycosides, have been implicated as a risk factor for Clostridium difficile infection (CDI) with the greatest risk being attributed to second and third generation cephalosporins. ,, Clindamycin has also been implicated as a significant risk factor for many years, compounded by a multi-state outbreak of clindamycin resistant C. difficile in the USA.  Fluoroquinolones were, until recently, perceived to be low risk for Clostridium difficile associated diarrhea (CDAD).  The current increase in the incidence of CDI also appears to coincide with a widespread increased use of proton-pump inhibitors (PPI).  Advanced age, malnutrition, female gender, and medical comorbidities tend to diminish host protective response to C. difficile in adults,  and may be associated with more severe infection. Immunocompromised state, presence of inflammatory bowel disease, ,, and acute kidney injury  related to C. difficile also portend a worse prognosis and should be treated as severe in practice. The presence of associated leukocytosis above 35,000 cells/mm 3 , fever, hypotension, mental status changes, elevated serum lactate levels >2.2 mmol/L, end-organ failure, or admission to the Intensive Care Unit, define severe-complicated disease,  with predicted 20-30% mortality. Rarely, C. difficile may result in an ileus with abdominal distention but little to no diarrhea. This presentation tends to herald a more severe course and should also be treated as severe-complicated disease.  Most epidemics occur in the hospital setting and in long-term care facilities. , C. difficile is known to spread via the fecal-oral route by ingestion of acid-resistant spores,  therefore healthcare personnel carrying it on their hands might transfer it to the patient. But this infection can be treated if diagnosed well on time. Treatment includes the stoppage of inciting antibiotics if possible, to allow regeneration of the normal gut microflora, and starting an antibiotic with activity against C. difficile. Initial therapies based on severity of disease include metronidazole for mild-moderate disease, vancomycin for severe disease, or a combination of the two for severe-complicated disease.  Fecal microbiota tranpslantation, in which donor feces is infused into a patient's gastrointestinal lumen, results in a cure rate of approximately 90% in recurrent CDI.  A good clinical suspicion in patient with co morbidities developing diarrhea during hospital stay can help reduce the burden of this treatable morbid infection. Our aim of doing this study was to determine the prevalence of this infection in our tertiary care hospital, so as to monitor its burden in future.
| Aim and Objectives|| |
To determine the prevalence of CDI in a tertiary care hospital in North India.
| Subjects and Methods|| |
A retrospective study was conducted in the department of Microbiology in a tertiary care hospital in North India. A total of 195 stool samples from symptomatic patients developing diarrhea during their hospital stay, received over a period of 2 years from 1 st June 2010 to 1 st June 2012 were included in the study. An enzyme immunoassay was performed for the qualitative determination of toxins A and B from C. difficile in stool samples using RIDASCREEN C. difficile toxin A/B (C0801) kit which uses monoclonal antibodies against toxins A and B of C. difficile in a sandwich type of ELISA method to detect the presence of toxin A and B of C. difficile in the stool sample with a sensitivity of 89.7%, specificity of 96.8%, positive predictive value of 81.3%, and negative predictive value of 98.4%.
| Results|| |
A total of 13 (6.67%) stool samples out of 195 samples processed were positive for the presence of C. difficile toxins A/B. Presence of predisposing risk factors in all of these patients is mentioned in the [Table 1] given below. Out of 13 patients, 8 (61.54%) had comorbidities like diabetes mellitus type 2, chronic kidney disease, and hypertension. Age of 9 (69.23%) patients was above 50 years. One patient was a diagnosed case of human immune deficiency virus (HIV), therefore immunocompromised already while two others were on steroids and antifungal therapy. Most of these [6 (46.15%)] patients had frequent hospitalizations over a period of 6 months. Time period after which they developed CDI during hospital stay ranged from 4 to 9 days. All the patients were administered >3 broad spectrum antibiotics (like Chloramphenicol, Carbapenems, Fluoroquinolones, Cephalosporins, Aminoglycosides) and proton pump inhibitors.
|Table 1: Percentage distribution of patients for different risk factors favoring CDAD|
Click here to view
| Discussion|| |
CDI has existed for quite some time now. There have been studies done on this previously. An early report found 21/93 (22.58%) antibiotic-associated diarrhea cases positive for C. difficile by culture and toxin assay in Nehru Hospital in 1983-1984.  In Calcutta, C. difficile was isolated in 38/341 (11.14%) hospitalized patients with acute diarrhea over 1 year.  A hospital in Delhi reported CDI in 26/156 (16.67%) diarrheal hospitalized patients, detected by culture and toxin A EIA.  A retrospective review by Ingle et al. in a Mumbai hospital found that 17/99 (17.17%) patients between 2006 and 2008 were diagnosed with CDI by toxin A/B EIA.  Our study shows less prevalence in comparison to previous studies, but we had a small sample size to comment on this accurately. More and more clinicians need to be sensitized about this entity that has been in existence for long but which is ignored often. More no of samples being sent to us can help us build a better data base for our own hospital.
C. difficile is acquired via the fecal-oral route by ingestion of acid-resistant spores. Therefore, maintenance of appropriate hand-hygiene by healthcare workers by washing hands with soap and water to remove spores and isolation of patients with acute diarrhea can limit spread in the hospital.  A hospital in India introduced control measures including disinfection of surfaces, rapid detection of C. difficile by toxin assays, isolation of patients, controls on prescription of antibiotics, and education of staff members. The incidence of CDI (initially 15% among cases of nosocomial diarrhea) was reduced by 50% while the number of tests requested increased as health workers became more aware of CDI. 
| Conclusion|| |
The dramatic changes in the epidemiology of CDI during recent years, with increase in its incidence and severity in several countries, have made CDI a global public health challenge. Various studies mentioned above show a prevalence rate between 11-22%. Lower prevalence rate revealed from our study (6.7%) makes it imperative to maintain a strict surveillance in our patients to ensure opportune detection and treatment. Prevalence of C. difficile diarrhea more in patients on long-term antibiotics, gastric acid suppression drugs, and with underlying comorbidities makes it important to identify such patients acquiring diarrhea on prolonged stay in hospital and screening them for CDI. Reduction in inappropriate use of gastric acid suppression drugs and antibiotics in patients may not only prove beneficial in reducing the risk of CDAD but also significantly decrease patient morbidity and healthcare costs. Since many antibiotics like clindamycin, amoxicillin, ampicillin, cephalosporins, and quinolones can cause CDI, all antibiotics should be used prudently in sense with the hospital antibiotic stewardship program. There should be a reduction in inappropriate use of gastric acid suppression drugs. Because C. difficile spreads via hands from person to person, so desirable level of practices should be followed like thorough cleaning, contact precautions, and hand washing. Probiotics, which help restore a healthy balance to the intestinal tract, when used in conjunction with antibiotics, might help prevent recurrent CDI. So, this can be concluded from our study that "suspect, inspect, treat and prevent" are the key points that one should remember.
| References|| |
Kelly CP, LaMont JT. Clostridium difficile
-more difficult than ever. N Engl J Med 2008;359:1932-40.
Edlund C, Nord CE. Effect of quinolones on intestinal ecology. Drugs 1999;58 Suppl 2:65-70.
Johnson S. Recurrent Clostridium difficile
infection: A review of risk factors, treatments, and outcomes. J Infect 2009;58:403-10.
Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, et al
. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile
-associated diarrhea: A cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254-60.
Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile
and serum levels of IgG antibody against toxin A. N Engl J Med 2000;342:390-7.
Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile
diarrhoea. Lancet 2001;357:189-93.
Brandt LJ. American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile
infection. Am J Gastroenterol 2013;108:177-85.
Nord CE, Kager L, Heimdahl A. Impact of antimicrobial agents on the gastrointestinal microflora and the risk of infections. Am J Med 1984;76:99-106.
Golledge CL, McKenzie T, Riley TV. Extended spectrum cephalosporins and Clostridium difficile
. J Antimicrob Chemother 1989;23:929-31.
Wilcox MH, Freeman J, Fawley W, MacKinlay S, Brown A, Donaldson K, et al
. Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile
diarrhoea. J Antimicrob Chemother 2004;54:168-72.
Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile
infection. Clin Infect Dis 2008;46 Suppl 1:S19-31.
Johnson S, Samore MH, Farrow KA, Killgore GE, Tenover FC, Lyras D, et al
. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile
in four hospitals. N Engl J Med 1999;341:1645-51.
Spencer RC. The role of antimicrobial agents in the aetiology of Clostridium difficile-
associated disease. J Antimicrob Chemother 1998;41 Suppl C: 21-7.
Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007;102:2047-56.
Berg AM, Kelly CP, Farraye FA. Clostridium difficile
infection in the inflammatory bowel disease patient. Inflamm Bowel Dis 2013;19:194-204.
Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al
. Impact of Clostridium difficile
on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:345-51.
Nguyen GC, Kaplan GG, Harris ML, Brant SR. A national survey of the prevalence and impact of Clostridium difficile
infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008;103:1443-50.
Khanna S, Keddis MT, Noheria A, Baddour LM, Pardi DS. Acute kidney injury is an independent marker of severity in Clostridium difficile
infection: A nationwide survey. J Clin Gastroenterol 2013;47:481-4.
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.
Johnson S, Clabots CR, Linn FV, Olson MM, Peterson LR, Gerding DN. Nosocomial Clostridium difficile
colonisation and disease. Lancet 1990;336:97-100.
Simor AE. Diagnosis, management, and prevention of Clostridium difficile
infection in long-term care facilities: A review. J Am Geriatr Soc 2010;58:1556-64.
Burke KE, Lamont JT. Clostridium difficile
infection: A worldwide disease. Gut Liver 2014;8:1-6.
Burke KE, Lamont JT. Fecal transplantation for recurrent Clostridium difficile
infection in older adults: A review. J Am Geriatr Soc 2013;61:1394-8.
Ayyagari A, Sharma P, Venkateswarlu, Mehta S, Agarwal KC. Prevalence of Clostridium difficile
in pseudomembranous and antibiotic-associated colitis in north India. J Diarrhoeal Dis Res 1986;4:157-60.
Niyogi SK, Bhattacharya SK, Dutta P, Naik TN, De SP, Sen D, et al
. Prevalence of Clostridium difficile
in hospitalised patients with acute diarrhoea in Calcutta. J Diarrhoeal Dis Res 1991;9:16-9.
Dhawan B, Chaudhry R, Sharma N. Incidence of Clostridium difficile
infection: A prospective study in an Indian hospital. J Hosp Infect 1999;43:275-80.
Ingle M, Deshmukh A, Desai D, Abraham P, Joshi A, Rodrigues C, et al
. Prevalence and clinical course of Clostridium difficile
infection in a tertiary-care hospital: A retrospective analysis. Indian J Gastroenterol 2011;30:89-93.
Chaudhry R, Joshy L, Kumar L, Dhawan B. Changing pattern of Clostridium difficile
associated diarrhoea in a tertiary care hospital: A 5 year retrospective study. Indian J Med Res 2008;127:377-82.