Excessive reliance on molecular tests for Clostridium difficile infection, without testing for toxins and making a careful clinical assessment, is likely to result in overdiagnosis, overtreatment and excessive healthcare costs, a new study suggests.

Researchers led by Dr Christopher Polage analysed the laboratory findings in 1,416 inpatients at the University of California Davis Medical Center who were tested for the infection.

There were 21% who were positive by PCR and 45% positive for toxins on enzyme immunoassay (EIA).

Patients who were PCR-positive but were free of toxin had a lower C. difficile bacterial load and less antibiotic exposure, faecal inflammation and diarrhoea than those who were positive on both tests.

There were no CDI-related complications in those positive by PCR alone compared to 10 with complications in those who were also toxin-positive.

Recurrent infection was a contributing factor to death within 30 days in one and 11 patients in these two groups, respectively.

“Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C. difficile by either method,” Dr Polage said.

A commentary on the report, published in JAMA Internal Medicine, concluded that no laboratory test was sufficient to diagnose C. difficile infection – as opposed to non-pathogenic colonisation.

“While a diagnostic assay may indicate the absence or presence of the organism or its toxins, the test by itself does not determine who does or does not have CDI,” it said.

“One of the challenges in diagnosing CDI is that there are more asymptomatic C. difficile carriers than there are people with CDI in the community and in the hospital.

“It is estimated 3% to 7% of the healthy adult population are colonised.”

The best test to diagnose CDI remains unknown, the commentary stated, and all available diagnostic assays have advantages and disadvantages.

 This new study “contributes to the mounting evidence that most additional positive results of PCR-based C. difficile diagnostics compared with toxin EIAs represent asymptomatic colonization, not CDI.

“Regardless of which assay is used, it is best to remember to treat the patient, not the test.”

The Australasian Society for Infectious Diseases released guidelines on CDI diagnosis and treatment in 2011 (MJA 2011; 194: 353-358), listing the pros and cons of available diagnostic strategies but without clear recommendations on the optimal approach.

“The optimal diagnostic algorithm (for sensitivity and cost) is controversial,” they state.