Section 15
CNS Infections
Meningitis, Encephalitis & Fungal Therapy
25 AGENTS
Acyclovir
ZoviraxAntiviral
- Forms
- IV: 50mg/mL
- Dose
- HSV encephalitis: 10mg/kg IV q8h for 14-21 days (adjust for renal function; hydrate)
- MOA
- Inhibits viral DNA polymerase
Ceftriaxone
RocephinCephalosporin (3rd gen)
- Forms
- IV/IM: 250mg, 500mg, 1g, 2g vials
- Dose
- Bacterial meningitis: 2g IV q12h
- MOA
- Inhibits bacterial cell wall synthesis
Vancomycin
VancocinGlycopeptide
- Forms
- IV: 500mg, 1g, 1.5g, 5g, 10g vials
- Dose
- Meningitis (adjunct): 15-20mg/kg IV q8-12h, level/AUC-guided
- MOA
- Inhibits bacterial cell wall synthesis
Ampicillin
PrincipenAminopenicillin
- Forms
- IV: 250mg, 500mg, 1g, 2g vials
- Dose
- Listeria coverage: 2g IV q4h
- MOA
- Inhibits bacterial cell wall synthesis
Meropenem
MerremCarbapenem
- Forms
- IV: 500mg, 1g vials
- Dose
- Meningitis: 2g IV q8h
- MOA
- Inhibits bacterial cell wall synthesis
Dexamethasone (meningitis)
DecadronCorticosteroid
- Forms
- IV: 4, 10mg/mL
- Dose
- 0.15mg/kg IV q6h for 2-4 days; first dose before or with the first antibiotic dose
- MOA
- ↓Inflammatory response to bacterial lysis
Liposomal amphotericin B
AmBisomePolyene antifungal
- Forms
- IV: 50mg vial
- Dose
- Cryptococcal meningitis: 3-6mg/kg/day IV, given with flucytosine
- MOA
- Binds ergosterol, forms fungal membrane pores
Flucytosine
AncobonAntifungal
- Forms
- Cap: 250, 500mg
- Dose
- 100mg/kg/day PO divided q6h with amphotericin (adjust for renal function; monitor levels and CBC)
- MOA
- Converted to 5-FU, inhibits fungal DNA/RNA synthesis
Penicillin G
Pfizerpen (IV potassium)Penicillin (beta-lactam)
- Forms
- IV: potassium 5, 20 million units | premixed bags
- Dose
- Neurosyphilis: 18-24 million units/day IV (3-4 million units every 4h or continuous) x10-14 days | Meningitis (Listeria, susceptible pneumococcus): 24 million units/day divided every 4h
- MOA
- Binds penicillin-binding proteins, inhibits cell-wall synthesis
Cefepime
Maxipime4th-generation cephalosporin
- Forms
- IV: 1, 2g
- Dose
- Healthcare-associated or Pseudomonas meningitis: 2g IV every 8 hours (renal adjustment required)
- MOA
- Binds PBPs; good CSF penetration with inflamed meninges
Metronidazole
FlagylNitroimidazole antibiotic
- Forms
- IV: 500mg/100mL | Tab: 250, 500mg
- Dose
- Brain abscess (anaerobic coverage): 500mg IV/PO every 8 hours, usually with a third-generation cephalosporin
- MOA
- Reduced to radicals that damage anaerobe DNA; excellent CNS penetration
Ganciclovir
CytoveneAntiviral (nucleoside analog)
- Forms
- IV: 500mg vial
- Dose
- CMV encephalitis or ventriculitis: 5mg/kg IV every 12 hours (renal adjustment); often combined with foscarnet
- MOA
- Phosphorylated to ganciclovir triphosphate; inhibits CMV DNA polymerase
Foscarnet
FoscavirAntiviral (pyrophosphate analog)
- Forms
- IV: 24mg/mL (250, 500mL)
- Dose
- CMV CNS disease: 60mg/kg IV every 8h or 90mg/kg every 12h (renal adjustment); pre-hydrate
- MOA
- Directly inhibits viral DNA polymerase
Pyrimethamine
DaraprimAntiparasitic (DHFR inhibitor)
- Forms
- Tab: 25mg
- Dose
- Cerebral toxoplasmosis: 200mg load, then 50mg (under 60kg) or 75mg (60kg or more) daily with sulfadiazine and leucovorin
- MOA
- Inhibits Toxoplasma dihydrofolate reductase
Sulfadiazine
SulfadiazineSulfonamide antibiotic
- Forms
- Tab: 500mg
- Dose
- Cerebral toxoplasmosis: 1,000mg (under 60kg) or 1,500mg (60kg or more) every 6 hours with pyrimethamine and leucovorin
- MOA
- Inhibits dihydropteroate synthase
Trimethoprim-sulfamethoxazole
Bactrim / SeptraSulfonamide / folate-pathway antibiotic
- Forms
- IV: 16mg/mL TMP | Tab: 80/400, 160/800mg | Susp: 40/200mg per 5mL
- Dose
- Toxoplasmosis alternative: TMP 5mg/kg + SMX 25mg/kg every 12h | Listeria or Nocardia: TMP 15-20mg/kg/day divided every 6-12h
- MOA
- Sequential blockade of bacterial folate synthesis
Albendazole
AlbenzaAnthelmintic (benzimidazole)
- Forms
- Tab: 200, 400mg
- Dose
- Neurocysticercosis: 15mg/kg/day divided twice daily with food (max 1,200mg/day) x10-14 days, with corticosteroids and antiseizure therapy
- MOA
- Binds parasite tubulin, impairing glucose uptake
Praziquantel
BiltricideAnthelmintic
- Forms
- Tab: 600mg
- Dose
- Neurocysticercosis with multiple viable cysts: 50mg/kg/day divided three times daily x14 days, combined with albendazole
- MOA
- Increases parasite calcium permeability, causing tetanic paralysis
Doxycycline
VibramycinTetracycline antibiotic
- Forms
- Tab/Cap: 50, 75, 100, 150mg | IV: 100mg
- Dose
- Lyme neuroborreliosis: 100mg twice daily PO/IV for 14-21 days
- MOA
- 30S ribosomal inhibition; adequate CNS penetration
Isoniazid
INHAntimycobacterial
- Forms
- Tab: 100, 300mg | IV: 100mg/mL | Syrup: 50mg/5mL
- Dose
- TB meningitis: 5mg/kg/day (max 300mg) with pyridoxine; part of a 4-drug regimen
- MOA
- Inhibits mycolic acid synthesis (InhA); good CSF penetration
Rifampin
RifadinAntimycobacterial (rifamycin)
- Forms
- Cap: 150, 300mg | IV: 600mg
- Dose
- TB meningitis: 10mg/kg/day (max 600mg) in standard regimens; intensified dosing under study
- MOA
- Inhibits bacterial RNA polymerase
Pyrazinamide
PZAAntimycobacterial
- Forms
- Tab: 500mg
- Dose
- TB meningitis: 25mg/kg/day (max 2g) in the intensive phase
- MOA
- Pyrazinoic acid disrupts membrane energetics; excellent CSF penetration
Ethambutol
MyambutolAntimycobacterial
- Forms
- Tab: 100, 400mg
- Dose
- TB meningitis: 15-20mg/kg/day (max about 1.6g) in the intensive phase
- MOA
- Inhibits arabinosyl transferase (cell wall synthesis)
Fluconazole
DiflucanTriazole antifungal
- Forms
- Tab: 50, 100, 150, 200mg | IV: 200, 400mg
- Dose
- Cryptococcal meningitis consolidation: 400-800mg/day x8 weeks, then 200mg/day maintenance (after amphotericin/flucytosine induction)
- MOA
- Inhibits fungal CYP51 (ergosterol synthesis)
Voriconazole
VfendTriazole antifungal
- Forms
- Tab: 50, 200mg | IV: 200mg | Susp: 40mg/mL
- Dose
- CNS aspergillosis: 6mg/kg IV every 12h x2 doses, then 4mg/kg every 12h (or 200mg PO every 12h); guided by drug levels
- MOA
- Inhibits fungal CYP51; excellent CNS penetration