When the meningitis–encephalitis panel is negative: off-label joint infection PCR detects CTX-M ESBL–producing Proteus mirabilis in adult meningoencephalitis

Abstract Spontaneous Gram-negative bacillary meningitis in adults is rare and carries high mortality, particularly in elderly patients with significant comorbidities. Although multiplex meningitis-encephalitis (ME) panels have improved diagnostic turnaround time, their limited pathogen spectrum may reduce sensitivity for certain clinically relevant Gram-negative organisms. We report a 78-year-old man presenting with acute meningoencephalitis, septic deterioration, and cerebrospinal fluid (CSF) findings strongly suggestive of bacterial infection. Despite marked neutrophilic pleocytosis and elevated protein levels, the multiplex ME panel was negative. Blood cultures subsequently yielded Proteus mirabilis . Given the discordance between inflammatory CSF findings and routine molecular testing, following interdisciplinary consultation, an off-label BioFire ® Joint Infection multiplex PCR panel was performed directly on CSF. The assay identified Proteus mirabilis harboring a cefotaximase-Munich (CTX-M)-type extended-spectrum β-lactamase (ESBL) resistance determinant. Based on this result, antimicrobial therapy was escalated from ceftriaxone-based empiric treatment to meropenem prior to availability of phenotypic susceptibility data. Despite early pathogen identification and targeted antimicrobial therapy, the patient died due to multiorgan dysfunction secondary to severe sepsis. This case suggests a potential diagnostic limitation of standard ME panels in selected high-risk scenarios and indicates that selective off-label use of broader multiplex PCR platforms may provide additional clinically relevant information in carefully selected patients. In the setting of high clinical suspicion and negative routine multiplex testing, rapid resistance-gene detection may provide actionable information within a decisive therapeutic window and support timely antimicrobial optimization in severe Gram-negative central nervous system infections. Further studies are required to evaluate the diagnostic performance and clinical impact of such approaches. Written informed consent for publication was obtained from the patient’s next of kin, and the study was conducted in accordance with institutional and ethical standards. Clinical trial number Not applicable.