Evaluation of a lateral-flow GDH test to screen for Clostridium difficile infection

Clostridium difficile is a Gram-positive, anaerobic, spore-forming bacillus that causes severe diarrhoea and other intestinal disease and is a major nosocomial pathogen resulting in high rates of morbidity and mortality.1–13 It is the most serious cause of antibiotic-associated diarrhoea (AAD) and has been associated with a range of symptoms.2 Major risk factors include: antimicrobial therapy, age (?65 years), immunosuppression, nasogastric intubation and antinuclear medication.2 Asymptomatic carriage, mild watery diarrhoea, pseudomembranous colitis (PMC), toxic megacolon and ultimately death are all possible outcomes of exposure to the organism.3

Symptoms may appear immediately following antimicrobial therapy or several weeks after therapy is completed.2 The main feature of C. difficile infection (CDI) is diarrhoea, defined as loose stools two or three times in 24 hours,6 with stools having a typical malodorous smell.3 In those who develop CDI, clinical features can vary considerably, from mild diarrhoea to life-threatening PMC.5
 The clinical manifestations and pathological changes associated with CDI are attributed to the production of two exotoxins (toxins A and B) that have enterotoxic and cytotoxic properties, respectively.4 These toxins can be found in the faeces of 15–25% of patients with antibiotic-associated diarrhoea and in more than 95% of patients with PMC.2

Mild cases of C. difficile infection can often be cured by discontinuing the antibiotics responsible.13 In more serious cases, oral administration of metronidazole and, if that fails, then vancomycin are currently the treatments of choice. Relapses of C. difficile AAD have been reported in up to 20% of cases.13
 Accurate diagnosis of CDI is critical to patient management and control of the spread of infection. It is also necessary for monitoring the disease trends and tracking infection patterns, as well as monitoring the efficacy of intervention methods. Laboratory diagnosis of C. difficile has depended on the demonstration of TcdA or TcdB,8 and various tests are available. However, with raised public awareness and the prospect of financial penalties, laboratories are balancing accuracy, sensitivity, specificity with cost to produce the most effective testing algorithm. The Department of Health will soon to be releasing guidelines and recommendations with regard to testing algorithms, and a document has been released recently in relation to this, as an infection control advisory notice. This document recommended glutamate dehydrogenase (GDH) as a screening tool for the diagnosis of C. difficile.