How well does aztreonam penetrate the cerebrospinal fluid in an adult with suspected Gram‑negative meningitis, and what is the appropriate meningitis dosing?

Aztreonam CSF Penetration and Meningitis Dosing

Aztreonam achieves therapeutic CSF concentrations in Gram-negative meningitis with inflamed meninges, and the appropriate dosing is 2 grams IV every 6-8 hours in adults.

CSF Penetration Characteristics

Aztreonam demonstrates significantly enhanced CSF penetration when meninges are inflamed, achieving concentrations 4-fold higher than in non-inflamed meninges. 1

• In patients with inflamed meninges receiving a single 2g IV dose, aztreonam CSF levels were detectable at 1 hour post-infusion and remained above the MIC/MBC for most Gram-negative bacteria 1
• Mean CSF concentrations in non-inflamed meninges ranged from 1.1-3.0 mcg/mL (600mg dose) and 2.3-4.7 mcg/mL (1200mg dose) in animal models 2
• With meningeal inflammation, CSF concentrations increased dramatically to 10.2-14.6 mcg/mL (600mg dose) and 29-40 mcg/mL (1200mg dose) 2

Recommended Dosing for Meningitis

For adults with Gram-negative meningitis, administer aztreonam 2 grams IV every 6 hours. 1

• This dosing regimen maintains CSF concentrations above inhibitory and bactericidal levels for susceptible Gram-negative organisms throughout the dosing interval 1
• Pediatric dosing: 50 mg/kg every 6-8 hours for children >2 years; 30 mg/kg every 6-8 hours for infants 3

Clinical Efficacy Data

Aztreonam demonstrated microbiologic cure in 73 of 77 patients (95%) with confirmed Gram-negative meningitis caused by susceptible organisms. 3

• Most common pathogens successfully treated: Haemophilus influenzae (40 patients), Enterobacteriaceae (16 patients), Neisseria meningitidis (15 patients), and Pseudomonas species (6 patients) 3
• The four microbiologic failures were associated with either persistent intracerebral abscess or death within 48-72 hours of treatment initiation, not drug failure 3
• Animal models showed substantial CSF bacterial count reductions: 2.4 log10 CFU/mL (600mg) and 3.0 log10 CFU/mL (1200mg) over 6 hours 2

Comparison to Other Beta-Lactams

While aztreonam is effective, third-generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime) remain first-line agents for empirical Gram-negative meningitis due to broader clinical trial data. 4

• Ceftriaxone and cefotaxime are recommended as first-line therapy by the Infectious Diseases Society of America for bacterial meningitis 4
• Ceftazidime should be specifically considered when Pseudomonas aeruginosa is suspected 4
• Meropenem demonstrates equivalent outcomes to third-generation cephalosporins and is preferred for ESBL-producing organisms 4

Critical Clinical Considerations

Aztreonam is specifically useful for patients with severe beta-lactam allergies who cannot receive cephalosporins or carbapenems, as it has minimal cross-reactivity.

• Aztreonam only covers aerobic Gram-negative bacteria; it has no activity against Gram-positive organisms or anaerobes
• Combination therapy is essential for empirical meningitis treatment until culture results confirm a pure Gram-negative infection
• The drug must be administered at high doses (2g every 6 hours) to maintain adequate CSF concentrations throughout the dosing interval 1
• Surgical intervention for abscess drainage or device removal should be performed whenever possible, as antimicrobial therapy alone has suboptimal outcomes for complicated CNS infections 4, 5