Aztreonam for CNS Infections
Primary Recommendation
Aztreonam should NOT be used for CNS infections. Aztreonam has poor cerebrospinal fluid penetration and is not recommended for central nervous system infections, even when caused by susceptible gram-negative organisms 1, 2, 3.
Rationale and Evidence
Pharmacokinetic Limitations
- Aztreonam achieves inadequate CNS concentrations despite being widely distributed to other body tissues and fluids including bone, prostate, and other sites 3.
- The drug's distribution characteristics result in concentrations that may be present in CSF but are insufficient for reliable therapeutic effect against CNS pathogens 3.
- The average elimination half-life of 1.7 hours and volume of distribution of 0.18 L/kg limit sustained therapeutic levels in the CNS compartment 3.
Spectrum of Activity Considerations
- Aztreonam has exclusively gram-negative aerobic activity with no coverage against gram-positive organisms or anaerobes 1, 2, 4.
- CNS infections frequently involve gram-positive pathogens (particularly Staphylococcus and Streptococcus species) that aztreonam cannot cover 1.
- The drug binds poorly to penicillin-binding proteins of gram-positive and anaerobic bacteria, rendering it ineffective against these common CNS pathogens 3.
Alternative Approaches for Gram-Negative CNS Infections
For Carbapenem-Susceptible Organisms
- Meropenem is the preferred carbapenem for CNS infections due to lower seizure risk compared to imipenem 1.
- Meropenem can be safely dosed up to 6 g daily and has superior CNS penetration compared to aztreonam 1.
For Carbapenem-Resistant Gram-Negative CNS Infections
- Consider intrathecal or intraventricular colistin (125,000 IU once daily, with a loading dose of 500,000 IU advocated) combined with parenteral therapy for Acinetobacter baumannii CNS infections 5.
- Treatment should continue for 3 weeks with monitoring of CSF sterilization 5.
- Intrathecal or intraventricular aminoglycosides (amikacin 10-50 mg daily or tobramycin 5-20 mg daily) constitute an alternative if the strain is susceptible 5.
Critical Clinical Pitfalls
- Do NOT assume aztreonam will treat CNS infections simply because it is effective for systemic gram-negative infections—CSF penetration is the limiting factor 1, 2, 3.
- Do NOT use aztreonam monotherapy for any suspected CNS infection, as empiric coverage must include gram-positive organisms 1, 4.
- Combination therapy is mandatory if aztreonam is used for systemic infections in patients with potential CNS involvement, requiring addition of agents active against gram-positive bacteria 2, 4.
Appropriate Uses of Aztreonam (Non-CNS)
- Aztreonam combined with ceftazidime-avibactam is the preferred treatment for metallo-β-lactamase-producing carbapenem-resistant Enterobacterales in non-CNS sites, with 30-day mortality of 19.2% versus 44% for alternative regimens 6, 7.
- Aztreonam remains valuable for urinary tract infections, lower respiratory tract infections, intra-abdominal infections, and septicemia caused by susceptible aerobic gram-negative organisms 1, 2, 8.