An 8-year-old boy with acute lymphoblastic leukemia receiving maintenance chemotherapy is hospitalized due to fever and neutropenia. Treatment with broad spectrum intravenous antibiotics is begun and the patient's fever resolves. His neutrophil count increases with granulocyte colony-stimulating factor therapy and blood cultures remain negative. On day 5 of hospitalization, the patient experiences nausea, abdominal cramping, and 6-8 episodes of watery diarrhea. Temperature is 37.7 C (100 F). Physical examination shows mild lower abdominal tenderness without guarding or rebound tenderness. Stool testing for occult blood is negative. Which of the following is the single best stool test to establish the cause of this patient's diarrhea?

Question

An 8-year-old boy with acute lymphoblastic leukemia receiving maintenance chemotherapy is hospitalized due to fever and neutropenia.  Treatment with broad spectrum intravenous antibiotics is begun and the patient's fever resolves.  His neutrophil count increases with granulocyte colony-stimulating factor therapy and blood cultures remain negative.  On day 5 of hospitalization, the patient experiences nausea, abdominal cramping, and 6-8 episodes of watery diarrhea.  Temperature is 37.7 C (100 F).  Physical examination shows mild lower abdominal tenderness without guarding or rebound tenderness.  Stool testing for occult blood is negative.  Which of the following is the single best stool test to establish the cause of this patient's diarrhea?

Quizplus · Accepted Answer

This child who developed diarrhea, nausea, and abdominal cramping while on antibiotics should be tested for Clostridium difficile infection (CDI). Patients who develop acute diarrhea (≥3 loose stool in 24 hours), particularly those with risk factors (eg, hospitalization, antibiotic use), should have stool samples sent for evaluation. Diagnostic testing includes: Nucleic acid amplication test (NAAT): Uses a polymerase chain reaction to detect genes present in toxigenic strains (eg, toxin B-encoding gene). This test is highly sensitive and specific for toxigenic strains but does not distinguish active toxin production and may lead to overdiagnosis in asymptomatic carriers. Enzyme immunoassays (EIA): Uses antibodies to detect C difficile antigens or toxins. EIA for bacterial toxins is highly specific but has poor sensitivity as large amounts of toxin are required. In contrast, EIA for glutamate dehydrogenase (a bacterial antigen expressed by all C difficile isolates) has better sensitivity but cannot distinguish toxin-producing strains. NAAT is considered the most sensitive method for diagnosis of CDI in patients with clinical symptoms. EIA for bacterial toxins can be added as part of a multistep algorithm to increase specificity of active disease; however, it is not recommended for use alone (Choice B). (Choice A) Culture on sorbitol-MacConkey agar is used to diagnose Escherichia coli O157:H7 (ie, enterohemorrhagic E coli [EHEC]). EHEC presents with bloody diarrhea; this patient's nonbloody diarrhea and recent antibiotic exposure makes CDI more likely. (Choice C) Latex agglutination for viral antigens is used to diagnose rotavirus, which causes nonbloody diarrhea, vomiting, and fever; disease can be particularly severe in immunocompromised patients. However, incubation time is typically <48 hours, and it is unlikely that this patient would develop an infection after 5 days in the hospital. (Choice D) Modified acid-fast staining is used to diagnose cryptosporidium infection, which causes chronic diarrhea (particularly in HIV-infected patients). This patient's current hospitalization and antibiotic use make CDI more likely. (Choice E) Stool ova and parasites are used to diagnose intestinal parasites (eg, Giardia, Entamoeba). These can cause diarrhea, which can be particularly severe in immunocompromised patients, but are unlikely to occur after 5 days in the hospital. Entamoeba histolytica typically presents with bloody stool after travel to resource-limited countries. Educational objective: Clostridium difficile commonly presents with diarrhea and abdominal pain; hospitalization and antibiotic use increase the risk of contracting the disease. A nucleic acid amplication test is considered the most sensitive method for diagnosis of C difficile infection in patients with clinical symptoms.

An 8-Year-Old Boy with Acute Lymphoblastic Leukemia Receiving Maintenance Chemotherapy