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Moxalactam penetration into cerebrospinal fluid in patients with bacterial meningitis
Abstract:
Penetration of moxalactam into the cerebrospinal fluid was studied in 11 patients with bacterial meningitis undergoing treatment with other antibiotics. Moxalactam at a dose of 20 mg/kg was administered as three 30- to 45- min infusions at 8-h intervals, once between days 2 and 4 and a second time between days 11 and 20 of treatment with the other antibiotics. Serum and cerebrospinal fluid were sampled 60, 90, or 120 min after the third moxalactam dose for measurement of the concentration of this drug by high-performance liquid chromatography. The concentration of moxalactam in cerebrospinal fluid ranged from 1.5 to 11 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. These concentrations in cerebrospinal fluid were equal to or higher than the minimum inhibitor concentrations for Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), and most of the gram-negative bacilli except for Pseudomonas aeruginosa. These results show that moxalactam has good penetrability when the meninges are inflamed and that it might be considered in cases of bacterial meningitis when the susceptibility of the pathogen indicates its usefulness.
Insights
Moxalactam effectively penetrates the cerebrospinal fluid in patients with bacterial meningitis, reaching concentrations effective against common pathogens. This suggests its potential utility in treating meningitis when pathogen susceptibility is confirmed.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Bacterial meningitis remains a critical condition requiring effective antibiotic penetration into the central nervous system.
- Assessing antibiotic efficacy necessitates understanding drug concentrations within the cerebrospinal fluid (CSF).
Purpose of the Study:
- To evaluate the penetration and concentration of moxalactam in the CSF of patients with bacterial meningitis.
- To determine if CSF moxalactam levels are sufficient to inhibit common meningitis-causing pathogens.
Main Methods:
- 11 patients with bacterial meningitis received moxalactam (20 mg/kg) infusions.
- CSF and serum samples were collected at 60, 90, or 120 minutes post-infusion.
- High-performance liquid chromatography (HPLC) was used to measure moxalactam concentrations.
Main Results:
- CSF moxalactam concentrations ranged from 1.5 to 11 µg/ml.
- Achieved CSF concentrations met or exceeded minimum inhibitory concentrations (MICs) for key pathogens like Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.
- Effective against most gram-negative bacilli, excluding Pseudomonas aeruginosa.
Conclusions:
- Moxalactam demonstrates good penetration into inflamed meninges.
- Moxalactam is a potential therapeutic option for bacterial meningitis, contingent on pathogen susceptibility.
- Further consideration of moxalactam is warranted in specific bacterial meningitis cases.