Cerebrospinal fluid , antibiotic

Wald SL, McLaurin RL. Cerebrospinal fluid antibiotic levels during treatment of shunt infections. J Neurosurg 1980 52 41 6. 

Clinical Diagnosis A presumptive diagnosis can be made from by Gram or Wayson stain of lymph node aspirates, sputum, or cerebrospinal fluid. Plague can also be cultured. As for treatment, early administration of antibiotics is very effective. Supportive therapy for pneumonic and septicemic forms is required. 

Other antibiotics studied using RPC include chloramphenicol which could be determined at serum concentrations of about 0.5 /xg/ml using 0.1 ml samples ( 15) after extraction with ethyl acetate (316). A simple method for the analysis of chloramphenicol in serum and cerebrospinal fluid has been reported in which the analyte is extracted into methanol and the extract chromatographed with acetic acid-water methanol (1 62 37) as the mobile phase (i/7). 

Mezlocillin, piperacillin, and ticarcillin are parenteral antibiotics formulated as sodium salts, so prescribers must consider the sodium content of these antibiotics when administering them to patients with congestive heart failure. During their distribution phase, antipseudomonal penicillins achieve orfly low concentrations in the cerebrospinal fluid. Consequently, antipseudomonal penicillins are not among the drugs of first choice for meningitis therapy. 

The cephalosporins distribute in satisfactory concentrations to most tissues except the central nervous system. Only cefepime, cefuroxime (Zinacef), cefotaxime (Claforan), ceftriaxone Rocephin), and ceftazidime (Eortaz) achieve therapeutic concentrations in cerebrospinal fluid. Cefotaxime and ceftriaxone are antibiotics of first choice for the empirical treatment of brain abscess and meningitis. 

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli. 

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. 

Polymyxin B and colistin are not well absorbed from the gastrointestinal tract. An intramuscular injection of the polymyxins results in high drug concentrations in the liver and kidneys, but the antibiotic does not enter the cerebrospinal fluid (CSF), even in the presence of inflammation. 

C. Pyrazinamide is known to cause hyperuricemia and precipitate gouty arthritis. Pyrazinamide-induced gouty arthritis does not respond to uricosuric therapy with probenecid but may respond to acetylsalicylic acid. Cycloserine (A) can cause headaches, confusion, tremors, and seizures, possibly secondary to low levels of magnesium in the cerebrospinal fluid cycloserine should be avoided in patients with epilepsy and mental depression. It is not associated with hyperuricemia. Thiacetazone (B) is an antibiotic that is rarely used in tuberculosis. The most common adverse reactions are general rashes and GI intolerance. Its use is not associated with hy-... 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by C difficile. Parenteral doses must be administered intravenously. A 1-hour intravenous infusion of 1 g produces blood levels of 15-30 mcg/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal... 

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. 

The major concern of the emergency department physicians was the lethargy, hypotonia, and seizure activity. Initial laboratory studies revealed that the child had a normal complete blood count and smear. Other blood tests revealed metabolic acidosis with a bicarbonate concentration of 11 mEq/L (normal is 20-25 mEq/L) and an anion gap of 22 mEq/L (normal is < 15 mEq/L). His serum glucose, calcium, and magnesium concentrations were normal. To exclude the diagnosis of meningitis, a spinal tap was performed. The cell counts and chemistries of the cerebrospinal fluid were normal. The physicians considered that the child might have sepsis and administered antibiotics and intravenous fluids. Prior to administration of antibiotics, blood, urine, and cerebrospinal fluid were sent for bacterial culture. 

For a few drugs such as theophylline, saliva drug concentrations have been employed to supplement the collection of blood samples. However, the intersubject and intrasubject variability in saliva/plasma ratios have generally precluded the sole use of saliva drug concentrations to assess bioavailability. For some drugs such as cephalosporin antibiotics, clinical studies may also include a determination of appearance of drug in other body fluids such as the cerebrospinal fluid and bile. 

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). 

A consequence of the development of the large number of cephalosporins is that the molecular structures have become more and more complex. Alterations in the cephalosporin molecule have resulted in differences between cephalosporins in spectrum of activity, protein binding, peak serum level, serum half-life, route of excretion, cerebrospinal fluid levels and toxicity. Cephalosporins are semi-synthetic antibiotics derived from 7-aminocephalosporanic acid, which is also called the cephalosporin nucleus. The cephem ring ( nucleus") is composed of a (3-lactam ring fused with a dihydrothiazine ring (Figure 1). 

Boger W P 1959 The diffusion of sulfonamides into the cerebrospinal fluid a comparative study. Antibiotic Medicine and Clinical Therapy 6 32-40 Burchall J J 1973 Mechanism of action of trimethoprim-sulfamethoxazole. Journal of Infectious Diseases 128(suppl) 437-441... 

Haines SJ, Walters BC. Antibiotic prophylaxis for cerebrospinal fluid shunts A meta-analysis. Neurosurgery 1994 34 87-93. 

Whatever antibiotics may have achieved, it is a tenable view that sulfonamides given alone afford perfectly adequate treatment for this disease. They have the advantage over most antibiotics of attaining high concentrations in the cerebrospinal fluid Moreover, they are then uniformly distributed,... 

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