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Antibiotic Therapy

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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. [22] (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 Antibiotic(s)
Age 0-4 weeks Ampicillin plus cefotaxime or an aminoglycoside
Age 1-3 months Ampicillin plus cefotaxime plus vancomycin*
Age 3 months to 50 years Ceftriaxone or cefotaxime plus vancomycin*
Older than 50 years Ampicillin plus ceftriaxone or cefotaxime plus vancomycin*
Impaired cellular immunity Ampicillin plus ceftazidime plus vancomycin*
Neurosurgery, head trauma, or CSF shunt 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 Antibiotic(s)
Gram-positive cocci Vancomycin plus ceftriaxone or cefotaxime
Gram-negative cocci Penicillin G*
Gram-positive bacilli Ampicillin plus an aminoglycoside
Gram-negative bacilli 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)

Bacteria Susceptibility Antibiotic(s) Duration (Days)
S pneumoniae Penicillin MIC < 0.1 mg/L Penicillin G 10-14
MIC 0.1-1 mg/L Ceftriaxone or cefotaxime
MIC >2 mg/L Ceftriaxone or cefotaxime
Ceftriaxone MIC >0.5 mg/L Ceftriaxone or cefotaxime plus vancomycin or rifampin
H influenzae Beta-lactamase-negative Ampicillin  
Beta-lactamase-positive Ceftriaxone or cefotaxime
N meningitidis ... Penicillin G or ampicillin  
L monocytogenes ... Ampicillin or penicillin G plus an aminoglycoside 14-21
S agalactiae ... Penicillin G plus an aminoglycoside, if warranted 14-21
Enterobacteriaceae ... Ceftriaxone or cefotaxime plus an aminoglycoside  
P aeruginosa ... Ceftazidime plus an aminoglycoside  

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.

Bacterial resistance, especially penicillin resistance among Streptococcus pneumoniae, has been increasing worldwide, with reported rates of 41-56% in Southeast Asia and the Far East. In a study over a 10-year period in a Brazilian infectious diseases hospital, 17% of pneumococcal isolates from meningitis cases were resistant to penicillin, and penicillin resistance was associated with higher case-fatality.[23]

In the United States, analysis of Surveillance Network isolates found that pneumococcal penicillin resistance prevalence was 34.8% in 2008 using the new Clinical Laboratory Standards Institute criterion for meningitis (≥0.12 μg/ml), and 12.3% using the old criterion (≥2 μg/ml) for CSF isolates.[24]

In addition, after the introduction of the conjugate pneumococcal vaccine, isolates with minimum inhibitory concentrations (MICs) of 1 and 2 μg/ml declined, whereas those with MICs of 0.12-0.5 increased, possibly signaling the loss of resistant vaccine serotypes and the acquisition of resistance by nonvaccine serotypes.[24]

The geographic distribution of antibiotic resistance is variable. Thus, knowledge of resistance patterns in the local community is important when deciding on empiric antibiotic therapy (see Medication).

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).

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