Rare bacterial infections and metagenomics: current diagnostic and therapeutic challenges—a literature review

This review aims to summarize the diagnostic and therapeutic challenges associated with rare bacterial infections, with particular focus on Whipple’s disease, melioidosis, Lemierre’s syndrome, and nocardiosis. It also evaluates the clinical utility of emerging molecular diagnostic techniques, particularly polymerase chain reaction (PCR) and metagenomic next-generation sequencing (mNGS), in improving pathogen identification. The primary research question concerns how advances in molecular microbiology may enhance the early diagnosis and targeted treatment of these infections. A narrative literature review with a structured search strategy was conducted. PubMed/MEDLINE and Scopus were searched for studies published between January 1998 and April 2026 using MeSH terms and keywords related to rare bacterial infections and molecular diagnostics. Eligible peer-reviewed articles in English or Polish, including original studies, reviews, meta-analyses, and selected case reports, were included. Data extraction and study selection were performed independently by two reviewers. Rare bacterial infections are frequently associated with delayed diagnosis due to nonspecific clinical manifestations, limited clinician awareness, negative culture results, and restricted access to advanced diagnostic methods. Molecular techniques improve detection sensitivity and identify pathogens not recoverable by routine culture. For metagenomic sequencing this comes at the cost of reduced specificity. In these infections the supporting evidence comes largely from case reports and small single-center series. Rare bacterial infections remain a significant diagnostic and therapeutic challenge. Broader implementation of advanced molecular diagnostic techniques, increased clinical awareness, and standardized diagnostic strategies are needed to reduce diagnostic delay. Whether this in turn reduces morbidity and mortality requires prospective evaluation.