Meningitis Medication

Updated: Oct 12, 2017
  • Author: Rodrigo Hasbun, MD, MPH; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication

Medication Summary

Begin empiric antibiotic coverage according to age and presence of overriding physical conditions. Empiric therapy also depends on prevalence of cephalosporin-resistant S pneumoniae (DRSP). In the United States, prevalence is considered high (>2-5%). Patients with severe penicillin (and presumed cephalosporin) allergies often require alternative therapy.

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Sulfonamides

Class Summary

Empiric antimicrobial therapy should cover all likely pathogens in the context of this clinical setting. Trimethoprim-sulfamethoxazole (TMP-SMX) is effective against many aerobic gram-positive and gram-negative bacteria, but its use in bacterial meningitis is limited to patients with Listeria monocytogenes meningitis who have a penicillin allergy.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

Trimethoprim and sulfamethoxazole work together to inhibit bacterial synthesis of tetrahydrofolic acid. Trimethoprim prevents the formation of tetrahydrofolic acid by binding to bacterial dihydrofolate reductase. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis. This results in inhibition of bacterial replication.

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Tetracyclines

Class Summary

Tetracyclines inhibit protein synthesis and, therefore, bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria. They are broad-spectrum bacteriostatic antibiotics that are used to treat infections caused by many gram-positive and gram-negative bacteria. They are contraindicated in children younger than 8 years of age, because they can cause tooth discoloration and bone growth retardation.

Doxycycline (Doryx, Adoxa, Doxy 100, Monodox, Oracea)

Doxycycline can be administered twice daily and is available in both intravenous (IV) and oral formulations. It is less likely to cause photosensitivity than other tetracyclines are. The maximum serum concentration of an IV dose of doxycycline occurs within 30 minutes of administration. The use of doxycycline in meningitis is limited to cases of Brucella or rickettsial meningitis.

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Carbapenems

Class Summary

Carbapenems inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins. Carbapenems, including meropenem, can be used for the treatment of meningitis.

Meropenem (Merrem IV)

A broad-spectrum carbapenem antibiotic, meropenem inhibits cell wall synthesis and has bactericidal activity. It is effective against most gram-positive and gram-negative bacteria. Compared with imipenem, meropenem has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci. It also has limited activity against highly-penicillin-resistant S pneumoniae isolates. [43]

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Fluoroquinolones

Class Summary

Fluoroquinolones inhibit bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. The use of fluoroquinolones is not recommended in patients with myasthenia gravis.

Second-generation fluoroquinolones, such as gatifloxacin and moxifloxacin, have excellent cerebrospinal fluid (CSF) penetration, and animal models suggest that they are effective in penicillin- and ceftriaxone-resistant pneumococcal meningitis. (Clinical trial data are available only for trovafloxacin, which has been removed from the market.)

Ciprofloxacin (Cipro, Cipro XR)

Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. Ciprofloxacin has an off-label indication for prophylaxis against Neisseria meningitidis meningitis after close contact with an infected person.

Moxifloxacin (Avelox)

Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Infectious Diseases Society of America guidelines recommend moxifloxacin plus vancomycin as an alternative to third-generation cephalosporins in meningitis caused by penicillin- and ceftriaxone-resistant S pneumoniae strains. [17]

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Antibiotics, Miscellaneous

Class Summary

Chloramphenicol inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.

Chloramphenicol

Chloramphenicol is effective against gram-negative and gram-positive bacteria. It can be used as a substitute in the treatment of a meningococcal infection in penicillin-allergic patients. Worldwide, however, meningococcal strains have shown increasing resistance to chloramphenicol, and patients with pneumococcal meningitis have poor outcomes with chloramphenicol.

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Glycopeptides

Class Summary

Vancomycin inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization. It is indicated for many infections caused by gram-positive bacteria.

Vancomycin

Vancomycin is a glycopeptide antibiotic that is active against staphylococci, streptococci, and other gram-positive bacteria. It exerts antibacterial activity by inhibiting biosynthesis of peptidoglycan and is the drug of choice for highly penicillin-resistant and ceftriaxone-resistant S pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). It is a component of empiric first-line therapy for meningitis associated with central nervous system (CNS) shunts.

Because of poor CSF penetration, a higher dose of vancomycin is required for meningitis than for other infections. In patients with renal impairment, the dose is adjusted on the basis of the creatinine clearance.

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Aminoglycosides

Class Summary

Aminoglycosides primarily act by binding to 16S ribosomal RNA within the 30S ribosomal subunit. They have mainly bactericidal activity against susceptible aerobic gram-negative bacilli.

Gentamicin

Although newer antibiotics are available, aminoglycosides such as gentamicin remain significant in treating severe infections. Aminoglycosides inhibit protein synthesis by irreversibly binding to the 30S ribosomal subunit. In meningitis or gram-negative meningitides, it must be administered intrathecally because of its poor CNS penetration. Dosing regimens are numerous; the dose is adjusted on the basis of the creatinine clearance and changes in the volume of distribution.

Streptomycin

Streptomycin has bactericidal action and inhibits bacterial protein synthesis. Susceptible organisms include Mycobacterium tuberculosis, Pasteurella pestis, Francisella tularensis, Haemophilus influenzae, Haemophilus ducreyi, donovanosis (granuloma inguinale), Brucella species, Klebsiella pneumoniae, Escherichia coli, Proteus species, Aerobacter species, Enterococcus faecalis, and Streptococcus viridans (in endocarditis, with penicillin). Streptomycin is always given as part of a total antituberculosis regimen.

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Penicillins, Amino

Class Summary

Ampicillin is a second-generation penicillin that is active against many strains of E coli, Proteus mirabilis, Salmonella, Shigella, and H influenzae.

Ampicillin

A bactericidal beta-lactam antibiotic, ampicillin inhibits cell wall synthesis by interfering with peptidoglycan formation. The drug is indicated for L monocytogenes and Streptococcus agalactiae (group B streptococcus [GBS]) meningitis, usually in combination with gentamicin

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Penicillins, Natural

Class Summary

Penicillins are highly active against gram-positive organisms.

Penicillin G aqueous (Crystapen, Penicillin G potassium, Penicillin G sodium)

A beta-lactam antibiotic, penicillin G inhibits bacterial cell wall synthesis, resulting in bactericidal activity against susceptible microorganisms. It is active against many gram-positive organisms and is the drug of choice for syphilitic meningitis and susceptible organisms (eg, N meningitidis and penicillin-susceptible S pneumoniae).

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Cephalosporins, 3rd Generation

Class Summary

Third-generation cephalosporins are less active against gram-positive organisms than first-generation cephalosporins are. They are highly active against Enterobacteriaceae, Neisseria, and H influenzae.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms but 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 (Fortaz, Tazicef)

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 1 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.

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Antivirals, CMV

Class Summary

Ganciclovir can be used to treat cytomegalovirus (CMV) meningitis in immunocompromised hosts.

Ganciclovir (Cytovene)

Ganciclovir is a synthetic guanine derivative that is active against CMV. An acyclic nucleoside analog of 2′-deoxyguanosine, it inhibits the replication of herpesviruses in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in virus-infected cells.

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Antivirals, Other

Class Summary

Antiviral agents interfere with viral replication; they weaken or abolish viral activity. They can be used in viral meningitis.

Acyclovir (Zovirax)

A prodrug activated by cellular enzymes, acyclovir inhibits the activity of herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) by competing for viral DNA polymerase and incorporation into viral DNA. Acyclovir is used in HSV meningitis.

Foscarnet (Foscavir)

Foscarnet is an organic analogue 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 dosages of 60 mg/kg IV every 8 hours and maintenance dosages of 90-120 mg/kg IV every 24 hours.

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Antifungals, Systemic

Class Summary

Antifungal 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 Streptomyces nodosus, amphotericin B 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 (ie, Candida albicans, Histoplasma capsulatum, and Cryptococcus neoformans).

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 S nodosus; it can be fungistatic or fungicidal. The drug binds to sterols (eg, 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.

Fluconazole (Diflucan)

Fluconazole has fungistatic activity. It is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.

Flucytosine (Ancobon)

Flucytosine is converted to fluorouracil after penetrating fungal cells and inhibits RNA and protein synthesis by competing with uracil. It is active against candidal and cryptococcal species and is used in combination with amphotericin B.

Itraconazole (Sporanox, Onmel)

Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.

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Antituberculous Agents

Class Summary

These agents are used in the management of mycobacterial disease in combination with other antituberculous 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. Addition of pyridoxine (6-50 mg/day) is recommended if peripheral neuropathies secondary to isoniazid therapy develop.

Pyrazinamide

Pyrazinamide is a pyrazine analogue of nicotinamide; it may be bacteriostatic or bactericidal against Mycobacterium tuberculosis, depending on the drug concentration attained at the site of infection. Pyrazinamide's mechanism of action is unknown.

Ethambutol (Myambutol)

Ethambutol diffuses into actively growing mycobacterial cells (eg, tubercle bacilli). It impairs cell metabolism by inhibiting the synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated. Mycobacterial resistance is frequent with previous therapy.

Ethambutol is used in combination with second-line drugs that have not been administered previously. It is administered every 24 hours until permanent bacteriologic conversion and maximal clinical improvement are observed. Absorption is not significantly altered by food.

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Vaccines, Inactivated, Bacterial

Class Summary

Inactivated bacterial vaccines are used to induce active immunity against pathogens responsible for meningitis.

Meningococcal (group A C Y and W-135) diphtheria conjugate vaccine (Menactra, Menveo)

This vaccine is composed of capsular polysaccharide antigens (groups A, C, Y, and W-135) of N meningitidis. Meningococcal vaccine may be used to prevent and control outbreaks of serogroup C meningococcal disease, according to Centers for Disease Control and Prevention (CDC) guidelines. It induces formation of bactericidal antibodies to meningococcal antigens.

The vaccine is used for active immunization against invasive meningococcal disease caused by inclusive serogroups. Although the vaccine induces antibody response for serogroup A in individuals as young as age 3 months, it is poorly immunogenic for serogroup C in recipients who are younger than age 18-24 months.

Meningococcal group B vaccine (Trumenba, Bexsero)

The vaccine is administered as a 3-dose series at months 0, 2, and 6 (Trumenba) or a 2-dose series given at least 1 month apart (Bexsero). It induces production of bactericidal antibodies directed against the capsular polysaccharides of serogroup B. It is indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B in individuals aged 10 through 25 years.

Pneumococcal polysaccharide vaccine polyvalent (Pneumovax 23)

This vaccine contains capsular polysaccharides of 23 pneumococcal types, which constitute 98% of pneumococcal disease isolates.

Pneumococcal vaccine 13-valent (Prevnar 13)

Capsular polysaccharide vaccine against 13 strains of S pneumoniae conjugated to nontoxic diphtheria protein. Includes serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.

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Corticosteroids

Class Summary

The use of steroids has been shown to improve overall outcome for patients with certain types of bacterial meningitis, such as H influenzae, tuberculous, and pneumococcal meningitis. If steroids are given, they should be administered before or during the administration of antimicrobial therapy.

Dexamethasone (Baycadron)

Dexamethasone has many pharmacologic benefits, such as stabilizing cell and lysosomal membranes. It increases surfactant synthesis, increases serum vitamin A concentrations, and inhibits prostaglandin and proinflammatory cytokines (eg, tumor necrosis factor alpha [TNF-α], interleukin [IL]-6, IL-2, and interferon gamma).

The timing of dexamethasone administration is crucial. If this agent is used, it should be administered before or with the first dose of antibacterial therapy, so as to counteract the initial inflammatory burst consequent to antibiotic-mediated bacterial killing. A more intense inflammatory reaction has been documented after the massive bacterial killing induced by antibiotics.

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Diuretics, Osmotic Agents

Class Summary

Mannitol produces osmotic diuresis and reduces intracranial pressure (ICP).

Mannitol (Osmitrol)

Mannitol may reduce subarachnoid-space pressure by creating an osmotic gradient between CSF in the arachnoid space and plasma. Doses of 1 g/kg IV have been used.

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Diuretics, Loop

Class Summary

Loop diuretics are used to reduce ICP and treat cerebral edema.

Furosemide (Lasix)

Furosemide is a loop diuretic that increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The proposed mechanisms for furosemide in lowering ICP include (1) lowering cerebral sodium uptake, (2) affecting water transport into astroglial cells by inhibiting the cellular membrane cation-chloride pump, and (3) decreasing CSF production by inhibiting carbonic anhydrase.

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Anticonvulsants, Hydantoins

Class Summary

Anticonvulsants are used to help aggressively control seizures (if present) in acute meningitis, because seizure activity increases ICP.

Phenytoin (Dilantin, Phenytek)

Phenytoin works on the motor cortex, where it may inhibit the spread of seizure activity. The activity of brainstem centers responsible for the tonic phase of grand mal seizures may also be inhibited. Dosing should be individualized. Doses of 15 mg/kg have been used.

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Anticonvulsants, Barbiturates

Class Summary

Phenobarbital elevates the seizure threshold, limits the spread of seizure activity, and is a sedative. Doses of 5-10 mg/kg have been recommended.

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.

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Anticonvulsants, Other

Class Summary

Anticonvulsants are used to help aggressively control seizures (if present) in acute meningitis, because seizure activity increases ICP.

Lorazepam (Ativan)

Lorazepam is a sedative hypnotic with a short onset of effect and a relatively long half-life. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the CNS, including the limbic system and the reticular formation. Doses of 0.1 mg/kg IV have been used to control seizures.

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