Antimicrobial Decision-Making in Culture-Negative Bacterial Meningitis with mNGS-Detected Prevotella-Dominant Anaerobic Signals: Two Case Reports and a Literature Review.

Anaerobic meningitis is uncommon and may be underrecognized when cerebrospinal fluid (CSF) culture is non-diagnostic, particularly after antimicrobial exposure or when anaerobic collection, transport, and incubation conditions are suboptimal. Metagenomic next-generation sequencing (mNGS) can provide complementary microbiological evidence in selected culture-negative central nervous system (CNS) infections, but low-biomass CSF results require explicit quality-control reporting and careful assessment of contamination and clinical plausibility. We report two culture-negative bacterial meningitis cases in which CSF mNGS showed a Prevotella-dominant anaerobic signal. Prevotella oris was the predominant species-level detection in both cases, accompanied by lower-abundance anaerobic co-detections. Because P. oris was not recovered by culture or independently confirmed by species-specific PCR, the results were classified as mNGS-supported Prevotella-dominant signals rather than confirmed monomicrobial P. oris meningitis. Both patients received case-specific antimicrobial therapy adjusted according to clinical status, serial CSF findings, neuroimaging evolution, and adverse-event monitoring. Case 1 required meropenem re-escalation after radiological progression and recurrent intracranial hypertension, whereas Case 2 improved after escalation to meropenem followed by the documented de-escalation to metronidazole. Both patients achieved favorable functional outcomes. These cases illustrate how CSF mNGS may be used as an adjunct when conventional microbiology is non-diagnostic, while emphasizing that sequencing signals, serial CSF changes, imaging, and treatment response must be interpreted together. The two observations do not establish P. oris causality or a standardized escalation/de-escalation regimen.