Abstract

In the last few decades, increasing use of antibiotics has dramatically increased the incidence of antibiotic-associated diarrhea. 

An unopposed homing of Clostridium difficile in intensive care unit (ICU) and wards puts forward new challenges for physicians. Development of diarrhea during or just after hospital stay, especially in old patients, is a typical clinical presentation of C. difficile diarrhea. Cytotoxin assay from tissue culture is a gold standard diagnostic test but its poor availability, high cost, time bound results and rapid development of life-threatening complications made us to think of a screening test. Demonstration of pathognomonic summit lesions and pseudomembrane with colonoscopy or sigmoidoscopy is relatively inexpensive, easily available and diagnosis is prompt. Our experience in few patients with colonoscopy makes us recommend it as a screening test for all clinically suspected patients. It is refuted as first-line investigation because of good number of false negative results but demonstration of pathognomonic lesions even in few patients saves the life with minimal expenditure and least time wastage before initiation of definitive treatment.

Introduction

Clostridium difficile is a Gram-positive, anaerobic, spore-forming bacillus with toxicogenic property. Its presence in intensive care units (ICUs), wards and now even in outpatients has put forward new challenges for treating physicians. Moreover, the cost of treatment and hospital stay increases only because of inadvertent antibiotic use and failure to follow aseptic precautions.

Clinical Features

Infection from C. difficile has a wide-spectrum of presentation i.e., from asymptomatic carriage to fulminant colitis. Pseudomembranous colitis (PC) is one of the rare but catastrophic presentations of C. difficile infection. Other uncommon presentations are non-PC and a milder form of C. difficile diarrhea. Collectively, these presentations are called C. difficile-associated diarrhea (CDAD). Besides being associated with C. difficile, PC can occur in less than 25% of other bacterial, viral and toxic causes of diarrhea, gastroenteritis and anorectal fistulas.

A patient of PC is typically an old age patient with history of antibiotic use during hospitalization, who develops recurrent diarrhea with or without blood in stools. Rarely, patient can present with hypoproteinemia and electrolyte imbalance, hypotension, toxic megacolon, severe sepsis or bowel perforation. Besides age and antibiotic use, other risk factors for PC are use of proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), chronic kidney disease (CKD) and methicillin-resistant Staphylococcus aureus (MRSA) co-infection. Rarely, abdominal and pelvic surgeries, Shigella infection, Crohn’s disease, neonatal necrotizing enterocolitis, intestinal obstruction, Hirschsprung’s disease and colonic carcinoma are associated with development of PC.

Diagnosis

The gold standard for diagnosis of C. difficile infection is cytotoxin assay that uses tissue culture. It takes 24-72 hours for reporting and also is not easily available even at tertiary healthcare centers. An alternative enzyme immunoassay (EIA) of toxin A and B of C. difficile is less sensitive with 10-20% false negative rate but is relatively easily available and gives result within 24 hours. Diagnostic colonoscopy or sigmoidoscopy is less sensitive with high false positive rates for asymptomatic and nonpseudomembranous type of CDAD. Presence of pathognomonic feature summit lesions and pseudomembrane on colonoscopy promptly make diagnosis of PC and usually do not require tissue culture or EIA. PC is sometimes a fatal condition and requires urgent initiation of treatment. Johal et al, in a study of 136 patients, suggest routine sigmoidoscopy in all clinically suspected patients where stool cytotoxin is negative for C. difficile. Although CDAD can present with normal appearing colonic mucosa, still a screening colonoscopy of patient with typical clinical presentation can easily clinch the diagnosis of PC and early institution of definitive treatment. Also, colonoscopy is available easily at small cities in India, where the facility of tissue culture and EIA for toxin A and B is not available. Colonoscopy is relatively inexpensive, allows assessment of disease severity and facilitates subsequent management. Ulcerative colitis, Crohn’s disease, infectious colitis and other similar conditions can be easily differentiated after colonoscopy. We present here two cases in which an early colonoscopy helped  us make out an early diagnosis and institute specific therapy that saved the lives of patients.

CASE 1

A 64-year-old female patient was shifted from orthopedic recovery ward to medicine ward for complaint of severe diarrhea since 5 days. She had been operated for hip fracture 20 days back and was in recovery phase. Most of her antibiotics had been stopped 3 days back when she developed first diarrheal episode. A presumptive diagnosis of antibiotic-associated diarrhea was made and she was put on probiotics. Her general condition continued to worsen so her stool was sent for culture and intravenous ciprofloxacin and metronidazole were started. Ultrasonography of abdomen was normal. 

Her colonoscopy was planned till report of culture was awaited. Her colonoscopy demonstrated multiple yellow white spots in transverse, descending and sigmoid colon with continuous membrane in rectum and anal canal. Her general condition rapidly started improving and she became asymptomatic after 10 days of intravenous and 4 days of oral metronidazole therapy. Stool culture report later confirmed presence of Clostridium species.

CASE 2

A 72-year-old female was admitted for bleeding per rectum, loose stools since past 3 weeks, pedal edema and altered senses since past 1 week. She was operated and given intravenous clindamycin for gangrene of right middle finger 2 weeks prior to development of loose stools. Her vitals were stable and except for presence of pallor and anasarca, general examination was normal. She was drowsy but no neurological deficit was observed. Abdomen was soft and nontender and there was no apparent organomegaly. Her hemoglobin was 3.5 gm%; serum albumin was 2.13 gm%, serum creatinine 0.75 mg%, and alanine aminotransferase/aspartate aminotransferase (ALT/AST) were 34/24 U/l. Escherichia coli × 106 was grown on stool culture. Total 6 units of blood transfusion was done and 100 mL of intravenous albumin was given for 6 days. Her general condition improved but except for diarrhea all symptoms subsided. Ultrasonography of abdomen showed an ill-defined mass of 2.6 × 3.2 cm in right iliac fossa with bilateral minimal pleural effusion. Her sigmoidoscopy demonstrated yellow white membranous layer on colonic mucosa with intermittent bleeding ulcer. 

In descending colon, the membrane scattered into spots and normal appearing intermittent mucosa. 

These lesions were summit lesions, which were pathognomonic of PC. She was started with vancomycin after which she improved dramatically in 48 hours and complete recovery occured in next 14 days.

Many more cases present to us but most of them respond very well to oral metronidazole therapy. 

So, based on above experience, we propose to use sigmoidoscopy as screening test for patients who are suspected to have antibiotic-associated diarrhea on clinical grounds. A keen observer can easily make diagnosis of PC on colonoscopy if typical lesions are present. The prime concern is to differentiate between antibiotic-associated diarrhea from C. difficile and antibiotic-associated diarrhea due to other causes. Table 1 differentiates between the clinical features and treatment of above two. 

Discussion

Pseudomembranous colitis is a rare but frequently fatal presentation of CDAD. Although gold standard for diagnosis of C. difficile infection is cytotoxin assay that uses tissue culture, still colonoscopy in an unprepared bowel, which is considered inappropriate for diagnosis, can be sometimes rewarding. Demonstration of pathognomonic summit lesions on colonoscopy makes prompt diagnosis and enables rapid institution of specific treatment and is thus lifesaving. We hereby recommend a diagnostic colonoscopy as screening test in all clinically suspected patients of antibiotic- associated diarrhea. It is easily available, makes prompt diagnosis and helps to differentiate from other similar conditions, is relatively less expensive, needs only a keen observer at cost of high false negative rate.

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Authors

Ashish Gautam, Assistant Professor, Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh

Prabhat Agrawal, Assistant Professor, Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh

Abhishek Raj, Assistant Professor, Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh

Ashwini K Nigam, Assistant Professor, Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh

Subhash chandra, Assistant Professor, Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh

Manish K Bansal,  Associate Professor, Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh