Is intrathecal (directly into the spinal canal) polymyxin (an antibiotic) effective for treating meningitis?

Intrathecal Polymyxin for Meningitis

Intrathecal polymyxin B is effective for treating meningitis caused by susceptible Gram-negative bacteria, particularly Pseudomonas aeruginosa, and should be administered when less toxic drugs are ineffective or contraindicated.

Indications for Intrathecal Polymyxin B

• Polymyxin B administered intrathecally is a drug of choice for meningitis caused by susceptible strains of Pseudomonas aeruginosa 1
• It is indicated for serious meningeal infections caused by Haemophilus influenzae when less potentially toxic drugs are ineffective or contraindicated 1
• Intrathecal polymyxin B is particularly valuable for treating multidrug-resistant (MDR) or extensively drug-resistant (XDR) Gram-negative bacterial meningitis 2

Dosing Recommendations

• For adults and children over 2 years of age: 50,000 units once daily intrathecally for 3-4 days, then 50,000 units once every other day for at least 2 weeks after cerebrospinal fluid cultures become negative and sugar content returns to normal 1
• For children under 2 years of age: 20,000 units once daily intrathecally for 3-4 days, then 25,000 units once every other day for at least 2 weeks after cerebrospinal fluid cultures become negative and sugar content returns to normal 1
• Polymyxin B should be dissolved in appropriate solutions (500,000 units in 10 mL 0.9% Sodium Chloride Injection for a 50,000 units per mL dosage unit) 1

Efficacy Data

• A systematic review of intrathecal/intraventricular polymyxin use found cure was achieved in 80% (51/64) of Gram-negative meningitis episodes, with higher success rates for Pseudomonas aeruginosa (87%) and Acinetobacter species (91%) 2
• Recent case reports demonstrate successful treatment of carbapenem-resistant Pseudomonas aeruginosa meningitis in pediatric patients using intrathecal polymyxin B without remarkable adverse events 3
• Combined intrathecal and intravenous polymyxin B-based therapy has shown effectiveness against multidrug-resistant Acinetobacter baumannii meningitis in pediatric patients 4

Safety Considerations

• Toxicity related to intrathecal administration of polymyxins was noted in 28% of patients in a systematic review, with meningeal irritation being the most common adverse effect 2
• Toxicity is generally dose-dependent and reversible; discontinuation of treatment was necessary in only a minority of cases 2
• Adverse reactions may include neurotoxicity and skin hyperpigmentation, but these are typically acceptable and reversible 4

Treatment Algorithm

1. Confirm diagnosis: Obtain cerebrospinal fluid (CSF) for culture and susceptibility testing 5
2. Initiate therapy: For suspected or confirmed Gram-negative meningitis resistant to conventional antibiotics, begin intrathecal polymyxin B at appropriate dose based on age 1
3. Monitor response: Follow CSF cultures, cell counts, protein and glucose levels to assess treatment efficacy 3
4. Continue treatment: Maintain therapy for at least 2 weeks after CSF cultures become negative and CSF parameters normalize 1
5. Monitor for toxicity: Watch for signs of meningeal irritation or neurotoxicity; dose reduction may be necessary if significant adverse effects occur 2

Important Caveats

• The ESCMID guidelines do not specifically recommend intrathecal polymyxin for routine use in bacterial meningitis, noting that intracranial pressure-based treatments need further evaluation 5
• Intrathecal polymyxin B should be administered ONLY for meningeal infections, not for other forms of central nervous system infections 1
• Combination therapy with systemic antibiotics may be more effective than intrathecal monotherapy, particularly for multidrug-resistant organisms 6
• The role of intrathecal polymyxin B alone versus combination therapy (intravenous and intrathecal) requires further study 6

Special Populations

• In pediatric patients with multidrug-resistant Acinetobacter meningitis, intrathecal polymyxin has been used successfully, though mortality remains high in this population 7
• For patients with plague meningitis, dual therapy with chloramphenicol and a fluoroquinolone is recommended rather than polymyxin 5