Polymicrobial Infections: A Comprehensive Review on Current Context, Diagnostic Bottlenecks and Future Directions

Worldwide, polymicrobial infections (PMIs) account for an estimated 20–50% of severe clinical infection cases, with biofilm-associated and device-related infections reaching 60–80% in hospitalized patients. This review discusses the clinical burden of major infections in which PMIs are almost inevitable, such as diabetic foot infections, intra-abdominal infections, pneumonia, and biofilm-associated device infections. Globally, the PMI landscape is diverse; however, the Indian subcontinent is a PMI hotspot where high comorbidities, endemic antimicrobial resistance, and underdeveloped diagnostic capacity elevate the risks of poor outcomes. Existing diagnostic like culture-based methods, PCR panels, sequencing, and biomarker-based assays are constrained by sensitivity, turnaround times (TATs), and high costs. Vulnerable populations, particularly neonates, the elderly, immunocompromised patients, and socioeconomically marginalized groups, show case-fatality rates 2-fold higher than monomicrobial infections in similar settings. Emerging diagnostic solutions include CRISPR-based multiplex assays, artificial intelligence-based metagenomic platforms, and sensitive biosensors with point-of-care applicability. These technologies show potential in reducing the TAT (<2 h) with high accuracy (>95%). However, their translation to real-world settings depends critically on affordability, integration into healthcare pathways, and supportive policy. This will provide equitable diagnostic access, particularly in low- and middle-income countries (LMICs).