Management of antimicrobial therapy in culture-negative post-neurosurgical meningitis caused by augmented renal...

Augmented renal clearance (ARC) is a well-recognized driver of subtherapeutic antibiotic concentrations in critically ill patients; however, its occurrence in elective neurosurgical populations remains unrecognized. Conventional serum creatinine and conventional intensive care unit (ICU)-based screening tools may fail to identify ARC, leading to antimicrobial failure.

A 51-year-old previously healthy woman underwent elective resection of a right cerebellar meningioma. Postoperatively, she developed culture-negative meningitis, with clinical and cerebrospinal fluid findings consistent with bacterial infection. Despite guideline-based vancomycin dosing (escalated to 18.5 mg/kg/dose), serial therapeutic drug monitoring (TDM) revealed persistently subtherapeutic trough concentrations (7.21 and 8.41 µg/mL; target 15-20 µg/mL). Serum creatinine levels remained normal (0.43 mg/dL); calculated creatinine clearance (Cockcroft-Gault) confirmed ARC (131.99 mL/min/1.73 m2), corroborated by 8-h urine collection (135.31 mL/min/1.73 m²). Conventional ICU-based ARC screening tools (ARC and ARCTIC scores) erroneously classified the patient as low risk. TDM-guided meropenem dose intensification (from 2 g every 8 h to 2.0 g every 4 h) and switching to linezolid (non-renally cleared, good CNS penetration) achieved therapeutic targets. A multimodal composite endpoint guided safe antibiotic cessation on postoperative day 23. The patient recovered fully without recurrence.

In culture-negative postoperative meningitis refractory to guideline-based therapy, ARC should be suspected as the underlying cause, specifically for renally eliminated medications. Calculated or estimated creatinine clearance values may underestimate true renal clearance in patients with ARC; therefore, proactive creatinine clearance measurement using timed urine collection is essential. Additionally, TDM-guided dosing and a multimodal composite endpoint are critical for optimal management.