This patient should begin empiric antimicrobial therapy with intravenous meropenem and vancomycin. He developed fever, nuchal rigidity, and altered mental status after a neurosurgical intervention, and analysis of the cerebrospinal fluid is consistent with bacterial meningitis following an invasive central nervous system (CNS) surgical procedure. In the setting of nosocomial meningitis, empiric antimicrobial therapy must cover a broad spectrum of pathogens, including gram-negative organisms (including Pseudomonas aeruginosa, Acinetobacter species, and Enterobacteriaceae) and Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]). Meropenem, a carbapenem, is a broad-spectrum, bactericidal β-lactam with excellent coverage of gram-positive and gram-negative organisms that effectively penetrates the CNS, making it an excellent agent for empiric treatment of nosocomial meningitis. Vancomycin is necessary to provide coverage for possible β-lactam gram-positive organisms, including MRSA. Therefore, the combination of meropenem and vancomycin is the most appropriate antibiotic regimen to cover the potential causative pathogens in this patient.

Because the combination of vancomycin and ceftriaxone, with or without ampicillin, would not provide adequate coverage for P. aeruginosa, this regimen would not be the most appropriate treatment choice in this patient.

Moxifloxacin may cover appropriate gram-negative and gram-positive organisms; however, fluoroquinolones have not been well studied for use in bacterial meningitis and are generally reserved for patients with an allergy to β-lactam antibiotics. Fluoroquinolones also do not provide empiric coverage for MRSA.