Is lactulose effective for testing for Clostridioides difficile (C. diff) infection?

From the Guidelines

Lactulose is not effective for testing for Clostridioides difficile (C. diff) infection. The appropriate tests for diagnosing C. diff infection are nucleic acid amplification tests (NAATs) that detect the genes for toxin production, enzyme immunoassays (EIAs) that detect C. diff toxins directly, or a two-step algorithm using glutamate dehydrogenase (GDH) antigen testing followed by toxin testing 1. Lactulose is actually a medication used to treat constipation and hepatic encephalopathy, not a diagnostic test. It works by drawing water into the intestine and lowering ammonia levels in the blood, respectively. For proper C. diff diagnosis, stool samples should be collected and sent to the laboratory for one of the aforementioned testing methods. Testing should only be performed on unformed stool samples from patients with clinically significant diarrhea (typically defined as 3 or more loose stools in 24 hours) 1. Using lactulose instead of these established testing methods would lead to missed diagnoses and inappropriate patient management.

Some key points to consider when testing for C. diff infection include:

• The diagnosis of CDI should be based on clinical signs and symptoms in combination with laboratory tests 1
• Stool testing should only be performed on diarrheal stools from at-risk patients with clinically significant diarrhea (≥ 3 loose stools in 24 h) with no obvious alternative explanation 1
• Nucleic acid amplification tests (NAATs) for C. difficile toxin genes appear to be sensitive and specific and may be used as a standard diagnostic test for CDI 1
• Glutamate dehydrogenase (GDH) screening tests for C. difficile are sensitive but do not differentiate between toxigenic and non-toxigenic strains 1
• EIA for toxin A/B is fast and inexpensive and has high specificity but it is not recommended alone due to its relatively low sensitivity 1

It's also important to note that repeat testing after a first negative sample during the same diarrheal episode may be useful only in selected cases with ongoing clinical suspicion during an epidemic situation or in cases with high clinical suspicion during endemic situations 1. Additionally, there is no clinical value in repeat CDI testing to establish cure; >60% of patients may remain C. difficile positive even after successful treatment 1.

In terms of treatment, oral vancomycin is recommended for severe, complicated or recurrent CDI, while oral metronidazole is recommended for mild to moderate disease 1. Fidaxomicin may be used when risk of recurrence is high, however cost may be prohibitive 1.

Overall, lactulose is not a suitable test for C. diff infection, and established testing methods such as NAATs, EIAs, and GDH antigen testing should be used instead.

From the Research

Effectiveness of Lactulose for Testing C. diff Infection

• There is no direct evidence in the provided studies to support the use of lactulose for testing Clostridioides difficile (C. diff) infection 2, 3, 4, 5, 6.
• The studies recommend using a multi-step approach for diagnosis, including a highly sensitive initial rapid test such as the enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) or nucleic acid amplification testing (NAAT), followed by confirmatory testing 2.
• Lactulose is not mentioned as a diagnostic tool or treatment option for C. diff infection in any of the provided studies.

Diagnostic Approaches for C. diff Infection

• A multi-step approach is recommended for diagnosis, including a highly sensitive initial rapid test such as EIA for GDH or NAAT, followed by confirmatory testing with EIA toxin A/B, which has high specificity 2.
• Direct detection of C. difficile toxins in feces using EIA assay is a common diagnostic method, but no single test is suitable as a stand-alone test confirming CDI 4.

Treatment Options for C. diff Infection

• Vancomycin, fidaxomicin, and metronidazole are commonly used antibiotics for treating C. diff infection, with vancomycin recommended as first-line therapy for an initial episode of mild/moderate or severe CDI 2, 4, 6.
• Fecal microbiota transplantation (FMT) is a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults and has shown efficacy in treating CDI and reducing its recurrence 3, 5, 6.