Cerebrospinal fluid , antibiotic penetration

The degree of penetration of the aminoglycosides into cerebrospinal fluid is proportional to the degree of inflammation of the meninges. However, aminoglycosides are best combined with the (3-lactams or other antibiotics in the treatment of meningitis. 

Blood-brain barrier Treatment of central nervous system infections, such as meningitis, depends on the ability of a drug to penetrate into the cerebrospinal fluid (CSF). The blood-brain barrier (see p. 8) ordinarily excludes many antibiotics. However, inflammation facilitates penetration and allows sufficient levels of many (but not all) antibiotics to enter the CSF. [Note For cure of meningitis, it is important that a bactericidal rather than a bacteriostatic effect is achieved in the CSF. Yet, this is not without its problems, since rapid bacteriolysis in the infected CSF will liberate high concentrations of bacterial cell walls and lipopolysaccharide that can exacerbate the inflammation. This has led to the use of adjunctive (simultaneous administration of) corticosteroids, which diminish the inflammatory process and neurologic sequelae.]... 

Distribution All of these antibiotics distribute very well into body fluids. However, adequate therapeutic levels in the cerebrospinal fluid (CSF), regardless of inflammation, are achieved only with the third generation cephalosporins (for example, ceftriaxone or cefotaxime are effective in the treatment of neonatal and childhood meningitis caused by Haemophilus influenzae). Cefazolin (se FA zo lin) finds application in orthopedic surgery because of its activity against penicillinase-producing Staphylococcus aureus, its half-life and its ability to penetrate bone. 

Distribution Erythromycin distributes well to all body fluids except the cerebrospinal fluid (CSF). It is one of the few antibiotics that diffuses into prostatic fluid and has the unique characteristic of accumulating in macrophages. It concentrates in the liver. Inflammation allows for greater tissue penetration. Similarly, clarithromycin and azithromycin are widely distributed in tissues. Serum levels of azithromycin are low the drug is concentrated in neutrophils, macrophages, and fibroblasts. 

Fosfomycin has relatively low toxicity. Its penetration into tissues, including bones and joints, and into the cerebrospinal fluid is good. When given orally (2-3 g/day), it can produce gastrointestinal distress when injected intramuscularly, it can cause local pain. Fosfomycin is recommended in daily doses of 4-16 g intravenously for the treatment of severe infections resistant to other commonly used antibiotics. Fosfomycin diffuses moderately well into bone tissue (2). 

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