Molecular techniques for diagnosis of Clostridium difficile infection: systematic review and meta-analysis

Abstract

Objective: To assess the usefulness of 2 rapid molecular diagnostic techniques, polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), in Clostridium difficile infection (CDI).

Methods: We conducted a systematic review and meta-analysis to evaluate the accuracy of PCR and LAMP in diagnosis of CDI, including studies that used toxigenic culture or cytotoxicity assay as reference standard.

Results: A search of PubMed and CinAHL medical databases yielded 25 PCR studies, including 11,801 samples that met inclusion criteria and 6 heterogeneous studies that evaluated LAMP. With toxigenic culture as a standard, pooled sensitivity was 0.92 (95% confidence interval [CI], 0.91-0.94); specificity, 0.94 (95% CI, 0.94-0.95); and diagnostic odds ratio, 378 (95% CI, 260-547). With cytotoxicity as a standard, pooled sensitivity was 0.87 (95% CI, 0.84-0.90); specificity, 0.97 (95% CI, 0.97-0.98); and diagnostic odds ratio, 370 (95% CI, 226-606).

Conclusion: Polymerase chain reaction is a highly accurate test for identifying CDI. Heterogeneity in LAMP studies did not allow meta-analysis; however, further research into this promising method is warranted.

FIGURE 1

Summary receiver operating curves (SROC) of studies using toxigenic culture (A) and cytotoxicity assay (B) as reference standard. With toxigenic culture reference standard, area under curve (AUC) is 0.99, with Q* of 0.95. With cytotoxicity assay reference standard, AUC is 0.99, with Q* 0.95. Individual studies and their relative weights are designated by the size of circles. Pooled results are represented by the diamond. Figure generated using Meta-DiSc software.

FIGURE 2

Estimated positive predictive value (PPV) (A) and negative predictive value (NPV) (B) of assays according to disease prevalence of stool tested. Median values for specificity and sensitivity were used to calculate these values. Reference standards are given in parentheses.

FIGURE 3

Diagnostic odds ratio (OR) of polymerase chain reaction (PCR) tests as compared with toxigenic culture (A) and cytotoxin assay (B). Studies that evaluated more than one PCR are noted in parentheses. BDGO = BD GeneOhm; CI = confidence interval; CX = Cepheid Xpert; LC = LightCycler; PG = Progastro.