Medication Summary
The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.
Antibiotics
Class Summary
These agents are used to treat or prevent infection caused by the most likely pathogen suspected or identified.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms but has excellent activity against susceptible pneumococcal organisms. It exerts an antimicrobial effect by interfering with the synthesis of peptidoglycan, a major structural component of the bacterial cell wall. It is an excellent antibiotic for the empiric treatment of bacterial meningitis.
Ceftazidime (Tazicef, Fortaz)
Ceftazidime is a third-generation cephalosporin with broad-spectrum activity against gram-negative organisms, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial replication.
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin that is used to treat suspected or documented bacterial meningitis caused by susceptible organisms, such as H influenzae or N meningitidis. Like other beta-lactam antibiotics, cefotaxime inhibits bacterial growth by arresting bacterial cell wall synthesis.
Gentamicin
Newer antibiotics are available, but aminoglycosides, such as gentamicin, remain significant in treating severe infections. Aminoglycosides inhibit protein synthesis by irreversibly binding to 30S ribosome. In meningitis or gram-negative meningitides, administer intrathecally because of poor CNS penetration. Dosing regimens are numerous; adjust the dose based on CrCl and changes in the volume of distribution.
Doxycycline (Doryx, Adoxa, Monodox)
Doxycycline inhibits protein synthesis and, therefore, bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Antivirals
Class Summary
These agents interfere with viral replication; they weaken or abolish viral activity.
Acyclovir (Zovirax)
A prodrug activated by cellular enzymes, acyclovir inhibits the activity of HSV-1, HSV-2, and varicella-zoster virus by competing for viral DNA polymerase and incorporation into viral DNA. Acyclovir is used in HSV meningitis.
Foscarnet (Foscavir)
Foscarnet is an organic analog of inorganic pyrophosphate that inhibits the replication of known herpesviruses, including CMV, HSV-1, and HSV-2. It inhibits viral replication at the pyrophosphate-binding site on virus-specific DNA polymerases. Foscarnet is used to treat CMV meningitis in immunocompromised hosts at induction doses of 60 mg/kg IV q8h and maintenance doses of 90-120 mg/kg IV q24h.
Valacyclovir (Valtrex)
Valacyclovir is a prodrug rapidly converted to the active drug acyclovir. It is more expensive than acyclovir but has a more convenient dosing regimen. The adult dosage is 500 mg orally twice a day for 5-10 days.
Risk of hyperkalemia is increased in patients taking angiotensin-converting enzyme (ACE) inhibitors, cyclosporine, and potassium-sparing diuretics. Use with caution in patients with renal failure (decrease the dose) and patients also taking nephrotoxic drugs. Valacyclovir is associated with onset of hemolytic uremic syndrome. Valacyclovir is a pregnancy category B drug.
Antifungals, Systemic
Class Summary
These agents are used in the management of infectious diseases caused by fungi.
Amphotericin B deoxycholate (Amphotericin B (conventional), Fungizone)
A polyene antibiotic produced by a strain of S nodosus, this drug can be fungistatic or fungicidal. It binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. The drug is used to treat severe systemic infection and meningitis caused by susceptible fungi (i.e., C albicans, H capsulatum, C neoformans). It is also available in liposomal (AmBisome) and lipid-complex (Abelcet) formulations. Amphotericin B does not penetrate the CSF well. Intrathecal amphotericin may be needed in addition.
Amphotericin B lipid complex (Abelcet)
This agent is amphotericin B in phospholipid complexed form; it is a polyene antibiotic with poor oral availability. Amphotericin B is produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. The drug binds to sterols (e.g., ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.
Flucytosine (Ancobon)
Flucytosine is converted to fluorouracil after penetrating fungal cells and inhibits RNA and protein synthesis. It is active against candidal and cryptococcal species and is used in combination with amphotericin B.
Fluconazole (Diflucan)
Fluconazole has fungistatic activity. It is a synthetic PO antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.
Antitubercular Agents
Class Summary
These agents are used in the management of mycobacterial disease in combination with other antitubercular agents.
Rifampin (Rifadin)
Rifampin is used in combination with other antituberculous drugs. It inhibits DNA-dependent bacterial, but not mammalian, RNA polymerase. Cross-resistance may occur
Isoniazid
Isoniazid is a first-line antituberculous drug that is used in combination with other antituberculous drugs to treat meningitis. It is usually administered for at least 12-24 months. A prophylactic dose of pyridoxine (6-50 mg/day) is recommended if peripheral neuropathies secondary to isoniazid therapy develop.
Pyrazinamide
Pyrazinamide is a pyrazine analog of nicotinamide; it may be bacteriostatic or bactericidal against M tuberculosis, depending on the drug concentration attained at the site of infection. Pyrazinamide's mechanism of action is unknown.
Corticosteroids
Class Summary
The use of steroids has been shown to improve the overall outcome of patients with certain types of bacterial meningitis, such as H influenzae, tuberculous, and pneumococcal meningitis. In general, corticosteroids are avoided but occasionally, glucocorticoids, such as dexamethasone, are useful when meningitis is associated with signs of increased intracranial pressure. If steroids are given, they should be administered prior to or during the administration of antimicrobial therapy. Meningitis from Vogt-Koyanagi-Harada syndrome responds to prednisone in moderate to high doses.
Dexamethasone (Baycadron)
Dexamethasone has many pharmacologic benefits such as stabilizing cell and lysosomal membranes. It increases surfactant synthesis, increases serum vitamin A concentrations, inhibits prostaglandin and proinflammatory cytokines (e.g., TNF-alpha, IL-6, IL-2, and IFN-gamma). The timing of dexamethasone administration is crucial. If used, it should be administered before or with the first dose of antibacterial therapy. This is to counteract the initial inflammatory burst consequent to antibiotic-mediated bacterial killing. A more intense inflammatory reaction has been documented following the massive bacterial killing induced by antibiotics.
Prednisone (Rayos)
Prednisone is an immunosuppressant used for treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.
Anticonvulsants, Other
Class Summary
Anticonvulsants help to aggressively control seizures if present in acute meningitis, because seizure activity increases intracranial pressure.
Phenytoin (Dilantin, Phenytek)
Phenytoin works on the motor cortex, where it may inhibit the spread of seizure activity. The activity of brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited. Doses should be individualized. Doses of 15 mg/kg have been used.
Phenobarbital
Phenobarbital elevates the seizure threshold, limits the spread of seizure activity, and is a sedative. Doses of 5-10 mg/kg have been recommended.
Acetaminophen (Aspirin-Free Anacin Extra Strength, FeverAll, Rapimed Junior, Tylenol)
Class Summary
Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.
Analgesics
Acetaminophen is the drug of choice for managing pain or fever in patients who have documented hypersensitivity to aspirin or NSAIDs, who have upper gastrointestinal (GI) disease, or who are taking oral anticoagulants.
