Multiplex PCR to Diagnose Gastrointestinal Infections: Key Limitations in Interpretation

Multiplex polymerase chain reaction (PCR) panels are increasingly used for the evaluation of acute diarrhea, providing rapid and sensitive detection of a broad range of enteric pathogens. However, their widespread adoption has created important interpretive challenges for clinicians. Positive results may reflect colonization, prolonged shedding, or organisms of uncertain pathogenicity rather than active infection, and current panels do not provide antimicrobial susceptibility or quantitative information. Incomplete pathogen coverage and false-positive detections may further complicate result interpretation, particularly in patients with mild or self-limited disease. Inappropriate test ordering or overinterpretation of results may lead to unnecessary antimicrobial therapy, delayed evaluation of non-infectious causes of diarrhea, and increased healthcare utilization. This review summarizes the key limitations of multiplex GI PCR panels and provides a practical framework for integrating molecular results with clinical presentation, disease severity, and patient risk factors to support informed management decisions in everyday clinical practice.