Drug of treatment for meningitis

Penicillin and cefotaxime are two of the antibiotics most frequently used to treat meningitis. But some bacteria (particularly Streptococcus pneumoniae) are becoming increasingly resistant to penicillin. So doctors often combine different types of antibiotics to try to kill all bacteria. For infants older than 1 month, treatment may include vancomycin and cefotaxime or ceftriaxone. For infants younger than 1 month, vancomycin may be added to the usual treatment of ampicillin and cefotaxime or ceftriaxone.

Vancomycin (in combination with cefotaxime, ceftriaxone, or rifampin) is also recommended for treatment of meningitis suspected or known to be caused by a highly penicillin-resistant strain of pneumococcus
The length and type of treatment varies depending on the kind of meningitis being treated, ranging from 1 - 3 weeks. The treatment for most cases of viral meningitis is aimed at reducing symptoms of fever and aches; sometimes acyclovir, an antiviral drug, may be given. If bacterial meningitis is suspected, antibiotics must be started immediately, even before results from lab tests have been returned. Some of the medications used for bacterial meningitis are:

Antibiotics, often in combination, including ampicillin, cephalosporins, gentamicin, vancomycin, or trimethoprim-sulfamethoxazole Corticosteroids to reduce inflammation Diazepam or phenytoin if seizures occur Rifampin is given to family members to reduce their risk of contracting the disease.

Bacterial meningitis is a neurologic emergency that is associated with significant morbidity and mortality. The initiation of empiric antibacterial therapy is therefore essential for better outcome. Ideal ED antibiotic therapy is based on a clearly identified organism on CSF Gram stain. Age and underlying conditions dictate empiric treatment in an ED patient without trauma or CNS instrumentation. Information presented in this article is taken from the 2003 edition of The Sanford Guide to Antimicrobial Therapy.[12] (See Table 7, Table 8, and Table 9, below.) Table 7. Recommended Empiric Antibiotics According to Predisposing Factors for Patients With Suspected Bacterial Meningitis (Open Table in a new window) Predisposing Feature Age 0-4 weeks Age 1-3 months Age 3 months to 50 years Older than 50 years Impaired cellular immunity Neurosurgery, head trauma, or CSF shunt Antibiotic(s) Ampicillin plus cefotaxime or an aminoglycoside Ampicillin plus cefotaxime plus vancomycin* Ceftriaxone or cefotaxime plus vancomycin* Ampicillin plus ceftriaxone or cefotaxime plus vancomycin* Ampicillin plus ceftazidime plus vancomycin* Vancomycin plus ceftazidime

*Vancomycin is added empirically to the initial regimen if the presence of penicillin-resistant S pneumoniae is suspected or if a high incidence of resistance is reported in the community. Table 8. Recommended Empiric Antibiotics for Patients With Suspected Bacterial Meningitis and Known CSF Gram Stain Results (Open Table in a new window) Gram Stain Morphology Gram-positive cocci Gram-negative cocci Gram-positive bacilli Gram-negative bacilli Antibiotic(s) Vancomycin plus ceftriaxone or cefotaxime Penicillin G* Ampicillin plus an aminoglycoside Broad-spectrum cephalosporin plus an aminoglycoside

*Use ceftriaxone if penicillin-resistant N meningitidis occurs in the community.

Ceftriaxone is preferred. Ceftazidime is used when Pseudomonas infection is likely (eg, neurosurgical procedures).

Table 9. Specific Antibiotics and Duration of Therapy for Patients With Acute Bacterial Meningitis (Open Table in a new window) Duration

Bacteria

Susceptibility

Antibiotic(s) (Days)

S pneumoniae

Penicillin MIC < 0.1 mg/L Penicillin G MIC 0.1-1 mg/L MIC >2 mg/L Ceftriaxone MIC >0.5 mg/L Ceftriaxone or cefotaxime Ceftriaxone or cefotaxime Ceftriaxone or cefotaxime plus vancomycin or rifampin Ampicillin Ceftriaxone or cefotaxime Penicillin G or ampicillin Ampicillin or penicillin G plus an aminoglycoside Penicillin G plus an aminoglycoside, if warranted Ceftriaxone or cefotaxime plus an aminoglycoside Ceftazidime plus an aminoglycoside

10-14

H influenzae

Beta-lactamase-negative Beta-lactamase-positive

N meningitidis L monocytogenes S agalactiae

... ... ...

7 14-21 14-21 21 21

Enterobacteriaceae ... P aeruginosa ...

Institute empiric antimicrobial therapy (ie, antibacterial treatment, or antivirals and antifungal therapy in selected cases) as soon as possible. This is usually based on the known predisposing factors and/or initial CSF Gram stain results. Appropriate antibiotic treatment for the most common types of bacterial meningitis should reduce the risk of death to less than 15%, although the risk is higher among elderly patients. The chosen antibiotic should attain adequate levels in the CSF. Achieving this usually depends on the drug's lipid solubility, its molecular size, its protein-binding capability, and the state of inflammation at the meninges. The penicillins, certain cephalosporins (ie, third- and fourth-generation cephalosporins), the carbapenems, fluoroquinolones, and rifampin provide high CSF levels. Monitor for possible drug toxicity during treatment (eg, with blood counts and renal and liver function monitoring). The dose of the chosen antimicrobial agent should always be adjusted based on the renal and hepatic function of the patient. At times, obtaining serum drug concentrations may be necessary to ensure adequate levels and to avoid toxicity in drugs with a narrow therapeutic index (eg, vancomycin, aminoglycosides). Once the pathogen has been identified and antimicrobial susceptibilities determined, the antibiotics may be modified for optimal targeted treatment.

Monitor for the occurrence of complications from the disease (eg, hydrocephalus, seizures, hearing defects) and its treatment (eg, drug toxicity, hypersensitivity).

Antibiotic therapy - Neonate to age 1 month

In neonates to age 1 month, the most common microorganisms are group B or D streptococci, Enterobacteriaceae (eg, E coli), and L monocytogenes. Primary treatment is a combination of ampicillin (age 0-7 d: 50 mg/kg IV q8h; age 8-30 d: 50-100 mg/kg IV q6h) plus cefotaxime 50 mg/kg IV q6h (up to 12 g/d). Alternative treatment is ampicillin (age 0-7 d: 50 mg/kg IV q8h; age 8-30 d: 50-100 mg/kg IV q6h) plus gentamicin (age 0-7 d: 2.5 mg/kg IV or IM q12h; age 8-30 d: 2.5 mg/kg IV or IM q8h). Most authorities recommend adding acyclovir 10 mg/kg IV q8h for herpes simplex encephalitis.

Antibiotic therapy - Age 1-3 months

In infants (1-3 mo), primary treatment is cefotaxime (50 mg/kg IV q6h, up to 12 g/d) or ceftriaxone (initial dose: 75 mg/kg, 50 mg/kg q12h up to 4 g/day) plus ampicillin (50-100 mg/kg IV q6h). Alternative treatment is chloramphenicol (25 mg/kg PO or IV q12h) plus gentamicin (2.5 mg/kg IV or IM q8h). If prevalence of cephalosporin-resistant S pneumoniae (DRSP) is greater than 2%, add vancomycin (15 mg/kg IV q8h). Strongly consider dexamethasone (0.4 mg/kg IV q12h for 2 d or 0.15 mg/kg IV q6h for 4 d) starting 15-20 minutes before first dose of antibiotics.

Antibiotic therapy - Age 3 months to 7 years

In older infants or young children (3 mo - 7 y), the most common microorganisms are S pneumoniae, N meningitidis, and H influenzae. Primary treatment is either cefotaxime (50 mg/kg IV q6h up to 12 g/d) or ceftriaxone (initial dose: 75 mg/kg, then 50 mg/kg q12h up to 4 g/d). If prevalence of DRSP is greater than 2%, add vancomycin (15 mg/kg IV q8h). In countries with low prevalence of DRSP, consider penicillin G (250,000 U/kg/d IM/IV in 3-4 divided doses). Due to DRSP, penicillin G is no longer recommended in the US. Alternative treatment (or if severely penicillin allergic) is chloramphenicol (25 mg/kg PO/IV q12h) plus vancomycin (15 mg/kg IV q8h). Strongly consider dexamethasone (0.4 mg/kg IV q12h for 2 d or 0.15 mg/kg IV q6h for 4 d) starting 15-20 minutes before the first dose of antibiotics.

Antibiotic therapy - Age 7-50 years

In an older child or an otherwise healthy adult (7-50 y), the most common microorganisms are S pneumoniae, N meningitidis, and L monocytogenes. In areas where prevalence of DRSP is greater than 2%, primary treatment is either cefotaxime (pediatric dose: 50 mg/kg IV q6h up to 12 g/d; adult dose: 2 g IV q4h) or ceftriaxone (pediatric dose: initial dose: 75 mg/kg, then 50 mg/kg q12h up to 4 g/day; adult dose: 2 g IV q12h) plus vancomycin (pediatric dose: 15 mg/kg IV q8h; adult dose: 750-1000 mg IV q12h or 10-15 mg/kg IV q12h). Some add rifampin (pediatric dose: 20 mg/kg/d IV; adult dose: 600 mg PO qd). If Listeria species is suspected, add ampicillin (50 mg/kg IV q6h). Alternative treatment (or if severely penicillin allergic) is chloramphenicol (12.5 mg/kg IV q6h: not bactericidal) or clindamycin (pediatric dose: 40 mg/kg/day IV in 3-4 doses; adult dose: 900 mg IV q8h: active in vitro but no clinical data) or meropenem (pediatric dose: 20-40 mg/kg IV q8h; adult dose: 1 g IV q8h: active in vitro but few clinical data; avoid imipenem, as it is proconvulsant). In areas with low prevalence of DRSP, use cefotaxime (pediatric dose: 50 mg/kg IV q6h up to 12 g/d; adult: 2 g IV q4h) or ceftriaxone (pediatric dose: 75 mg/kg initial dose then 50 mg/kg q12h up to 4 g/d; adult: 2 g IV q12h) plus ampicillin (50 mg/kg IV q6h). Alternative treatment (or if severely penicillin allergic) is chloramphenicol (12.5 mg/kg IV q6h) plus trimethoprim/sulfamethoxazole (TMP/SMX; TMP 5 mg/kg IV q6h) or meropenem (pediatric dose: 2040 mg/kg IV q8h; adult dose: 1 g IV q8h). Data are limited on the need for dexamethasone in adults, although there is support for its use in developed countries when S. pneumoniae is the suspected organism. Administer the first dose of dexamethasone (0.4 mg/kg q12h IV for 2 d or 0.15 mg/kg q6h for 4 d) 15-20 minutes before first dose of antibiotics.

Antibiotic therapy - Age 50 years and older

In adults older than 50 years or adults with disabling disease or alcoholism, the most common microorganisms are S pneumoniae, coliforms, H influenzae, Listeria species, Pseudomonas aeruginosa, and N meningitidis. Primary treatment if the prevalence of DRSP is greater than 2% is either cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h) plus vancomycin (750-1000 mg IV q12h or 10-15 mg/kg IV q12h). If CSF Gram stain shows gram-negative bacilli, use ceftazidime (2 g IV q8h). In areas of low prevalence of DRSP, use cefotaxime (2 g IV q4h) or ceftriaxone (2 g IV q12h) plus ampicillin (50 mg/kg IV q6h). Other options for treatment include meropenem, TMP/SMX, and doxycycline. Data are limited on the need for dexamethasone in adults, although there is support for its use in developed countries when S pneumoniae is the suspected organism and suspicion for TB or fungal etiologies is low. Administer the first dose of dexamethasone (0.4 mg/kg q12h IV for 2 d or 0.15 mg/kg q6h for 4 d) 15-20 minutes before the first dose of antibiotics. Go to the following articles for complete information on these topics: