Clostridium difficile associated diarrhea (CDAD) is a serious nosocomial illness, mostly seen in hospitalized adult patients. According to a recent review article, 2% of healthy individuals are colonized with Clostridium difficile bacilli; colonization rates are higher in hospitalized individuals and neonates. However, carriage of this organism decline to adult levels within the first few years of life. Most antibiotics predispose to symptomatic C. difficile infections and it rarely causes disease in the absence of prior antibiotic therapy(1). For unclear reasons, symptomatic CDAD is less common in neonates and infants(2,3). Mc Farland in his review cites reports of non-antibiotic associated C.difficile colitis in pediatrics, but most of these have been in neonatal intensive care unit, children with immunodeficiencies and those with cancers receiving antineo-plastic agents(4). We describe a case of potentially life-threatening, non-antibiotic associated Clostridium difficile diarrhea in a previously healthy 7 -week-old baby.

A previously healthy 7-week-old male infant presented to emergency department with a one day history of profuse bilious vomiting and lethargy, with the background of a ten day history of loose stools and faltering weight. His weight had been just above 9th percentile from birth and had fallen to the 2nd percentile. The antenatal history was uneventful, born in hospital at term by normal delivery. He passed meconium on day 1 and did not receive antibiotics in the neonatal period. He had been exclusively breast-fed and his mother was not on antibiotics.

On presentation, he was afebrile, looked wasted and dehydrated. He required fluid resuscitation and a third generation cephalosporin was commenced after a full sepsis screen. Differential diagnosis at this stage included sepsis and surgical gastrointestinal pathology.

Initial complete blood count and biochemistry including serum albumin was within normal limits. Cerebrospinal fluid, blood and urine cultures (suprapubic aspirate) were sterile as were stool specimens for bacteriology, virology and ova and cyst examination. Abdominal X-ray, USG and upper GI contrast study were done and reported as normal.

In view of the severity of his initial presentation, the negative cultures and normal gastrointestinal tract radiology, metabolic, endocrine and immunologic disorders were considered. His blood pH, glucose, lactate and ammonia were normal; urine amino acid and organic acids profile were normal. His serum cortisol and 17-hydroxyprogesterone were normal as were his immunoglobins, his lymphocyte phenotypes T cell -CD3+, CD4+, CD8+ and B cell CD19+ were marginally low, but judged not to be very significant by our immunologist as the total lymphocyte count was always normal. His chest X-ray showed a normal thymus. His repeat full blood work showed leukocytosis with white blood count of 21.05 × 109/L, and an elevated C- reactive protein of CRP 45 mg/L.

He was kept nil orally and full intravenous fluid maintenance started. He continued to have massive gastrointestinal losses, frequently requiring a fluid bolus immediately after a voluminous stool. He also required careful monitoring and correction of serum electrolytes.

Clostridium difficile toxin A and B (ELISA) was identified from a stool sample sent 30 hours after he had received the first dose of antibiotics. This stool specimen was negative for other enteric pathogens, viruses and parasites.

Intravenous antibiotics were discontinued, oral metronidazole commenced and continued for 7 days. His stool frequency started decreasing within 48 hours, but required total parental nutrition a further 10 days to improve his nutritional status. After six days, diarrhea gradually settled and breast-feeds were started. Repeat stool sample for C. difficile toxin was negative on day 7, 10 and 14, blood leukocyte count also returned to normal.

His course was complicated by upper respiratory tract infection with parainfluenza virus type 3 in the 3rd week of hospital stay. He finally gained weight and was discharged after a total of 22 days of hospital stay. Sixteen weeks after discharge he remains well and is thriving.

Clostridium difficile is a widely distributed obligate anerobe, gram-positive, spore-forming bacillus which produces two toxins, Toxin A and toxin B. Toxin A causes fluid secretion and mucosal damage while toxin B appears to have greater cytopathic effects in tissue culture but both are believed to play a role in the pathogenesis of disease(5).

Although there is a high carriage rate in neonates and young infants, symptomatic disease is uncommon(2). There are several theories to explain why they do not exhibit symptoms, despite high colonization rates. The absence of disease may be related to the immaturity of the toxin receptor sites, which are not able to bind the toxins(2). Neutralizing effect of maternal antibodies and immaturity of the neonatal immune system may play a role(2,3). The manifestations of C. difficile infection in children may range from asymptomatic colonization or mild self-limited diarrhea to toxic megacolon and severe colitis. In symptomatic cases, systemic symptoms and signs are usually present, which include malaise, anorexia, nausea, low-grade fever and leukocytosis(6). The diagnosis of CDAD is based on a combination of clinical symptoms, history, laboratory testing, and occasionally endoscopic evalua-tion. Due to asymptomatic carriage of C. difficile, the mere presence of the organism is not adequate to diagnose CDAD; toxin A and B identification is essential, the gold standard being tissue culture cytotoxin assay.

Although, majority of the cases are antibiotic related, occasionally, patients develop disease due to C. difficile in the absence of recent exposure to antibiotics. This most commonly occurs in patients with malignancies on antineoplastic drugs and hypogammaglobinemia(4). In this case no risk factor could be identified, it may be argued that C. difficile toxins was identified 30 hours after commencing on antibiotics. Usual time of presentation of illness is 4-8 days after first dose of antibiotic, but may be delayed as long as 21 days after antibiotics have been discontinued(7); this case had the symptoms of diarrhea and faltering weight 10 days before presentation and prior to antibiotics being commenced.

Literature does emphasis on leukocytosis as a marker of C.difficile colitis(6) and low albumin levels as an indicator of severe illness(8). Our case had leukocytosis for initial 6 days and a normal albumin level.

This case responded very well to oral metronidazole with no relapse, the other alternative is oral vancomycin, which is equally effective. The major problem with treatment of C. difficile disease is recurrence following initial therapy. Prospective trials have demonstrated recurrence of symptomatic associated diarrhea of 20% in patients, and can be managed effectively by repeating treat-ment(9). The use of steroids with good effect has been reported in refractory cases of colitis(10). Surgical therapy is rarely required for patients with C. difficile-associated disease.

Funding: None stated.

Competing interests: None stated.

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