Diffusion of ofloxacin into the cerebrospinal fluid in patients with bacterial meningitis

Stahl, J.-P.; Croizé, J.; Ma, Lefebvre; Jp, Bru; Guyot, Andrea; Leduc, Denis; Jb, Fourtillan; Micoud, M.

doi:10.1007/bf01661286

Cited by 27 publications

(7 citation statements)

References 3 publications

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“…Drancourt et al (3) found concentrations in CSF of 0.1 to 2.0 ,ug/ml 3 h after a 300-mg oral dose in patients with lymphocytic meningitis and 1.0 to 2.8 pug/ml in patients with purulent meningitis. Another report (13) studied nine patients with acute purulent meningitis who received 200 mg orally twice a day. After a few days of treatment, ofloxacin was measured in CSF and ranged from 0.9 to 4.5 jig/ml, corresponding to a penetration of 50 to 60%.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally

Bitar

Claes

Auwera

1989

Antimicrob Agents Chemother

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The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 ,ig/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 pg/ml) or 1 to 2 h after oral administration (1.7 to 4 ,ug/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae.

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Section: Discussionmentioning

confidence: 99%

“…The penetration of ofloxacin and other fluoroquinolones in the cerebrospinal fluid (CSF) has been studied in inflamed and noninflamed meninges from a small number of patients, and the concentrations were found to be higher than the MICs for most susceptible gram-negative bacilli (2,3,13,14).…”

mentioning

confidence: 99%

Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally

Bitar

Claes

Auwera

1989

Antimicrob Agents Chemother

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“…The new Table IV. Penetration of the fluoroquinolones into the CSF 105 fluoroquinolones penetrate well into the CSF: the ratio of more than 50% in the case of inflamed meninges is superior to that of the {:1-lactams (Stahl et al 1986). The half-life in CSF is similar to that in plasma.…”

Section: Penetration Into the Csfmentioning

confidence: 97%

Clinical Pharmacokinetics of the Newer Antibacterial 4-Quinolones

Neuman

1988

Clinical Pharmacokinetics

126

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Structural modification of the so-called 'first-generation' or 'urinary' quinolones has led to a considerable increase in their intrinsic antibacterial activity, together with marked changes in the pharmacokinetic properties. Tissue penetration is the most notable change, and the newer quinolones are comparable with the newer broad spectrum beta-lactams in their clinical spectrum of activity. Marketed compounds in the 4-quinolones group include pefloxacin, ofloxacin, enoxacin, ciprofloxacin and norfloxacin; many more compounds are in various stages of research and development. The 4-quinolones act by inhibition of bacterial DNA gyrase, a process which is pH and concentration dependent. The bactericidal activity can be partly abolished if protein synthesis is inhibited by chloramphenicol, or if RNA synthesis is inhibited by rifampicin (rifampin). The antibacterial spectrum of activity includes methicillin- and gentamicin-resistant staphylococci, multiresistant non-fermenters, all Enterobacteriaceae, Legionella, Neisseria species, Branhamella and Haemophilus influenzae. With the exception of norfloxacin, which is only 30 to 40% bioavailable from the oral route, the 4-quinolones are 80 to 100% bioavailable, absorption occurring within 1 to 3 hours. Food does not significantly alter Cmax, AUC or elimination half-life, although tmax, may be increased. The 4-quinolones are widely distributed throughout the body, with volumes of distribution greater than 1.5 L/kg. Protein binding is less than 30% in most cases. Penetration into most tissues is good. With the exception of ofloxacin and lomefloxacin (NY 198), which are metabolically stable, metabolism of the 4-quinolones occurs primarily at the C7 position in the piperazinyl ring. Biotransformation is extensive (85%) with pefloxacin, medium (25 to 40%) with ciprofloxacin and enoxacin, and low (less than 20%) with norfloxacin. Elimination half-lives vary between 3 and 5 hours (ciprofloxacin) and 8 to 14 hours (pefloxacin). Biliary concentrations of the 4-quinolones are 2 to 10 times greater than those in serum or plasma, with several compounds undergoing enterohepatic circulation. There is some evidence that ciprofloxacin, norfloxacin, ofloxacin and enoxacin have an active renal tubular excretion pathway. In impaired renal function, reduction of the glomerular filtration rate below 30 ml/min (1.8 L/h) is associated with an increase in elimination half-life and AUC, and a decrease in renal and total clearance of the 4-quinolones, and a decrease in 24-hour urinary recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The CSF penetration of quinolones was studied by several authors, both in patients with noninflamed and in patients with inflamed meninges (Bassaris et al 1986;Dow et al 1986;Kitzes-Cohen et al 1986;Stahl et al 1986;Stiibner et al 1986;Valainis et al 1986;Wolff et al 1984). The data suggest that quinolones penetrate faster into the CSF of patients with meningeal infections compared with non-infected patients.…”

Section: Cerebrospinal Fluidmentioning

confidence: 98%

Pharmacokinetic Disposition of Quinolones in Human Body Fluids and Tissues

Sörgel

Jaehde

Naber³

et al. 1989

Clinical Pharmacokinetics

103

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The unique pharmacokinetic properties as well as the body fluid and tissue penetration of quinolones are discussed.Quinolones are well absorbed from the gastrointestinal tract and are eliminated with considerable d{fJerences in their terminal half-lives. The major elimination pathways of quinolones are renal excretion and hepatic metabolism. Renally. these drugs undergo the potential excretion mechanisms (glomerular filtration. tubular secretion. reabsorption). In the liver. they are metabolised primarily by oxidation as well as by conjugative pathways. However. the metabolic pattern and extent of metabolism d{f!er significantly between individual agents.Alterations in the pharmacokinetic disposition of these agents in liver and renal failure as well as in elderly patients are observed as predicted from their excretion pattern. In addition. quinolones can interact with a number of other compounds at hepatic (e.g. with xanthine derivatives). renal (with probenecid) and gastrointestinal (with antacids) sites.The volume of distribution of quinolones is considerably higher than body volume. which suggests intracellular penetration. Studies on tissue penetration show that concentrations exceeding plasma levels are obtained in most tissues. The highest tissue/plasma concentration ratios are achieved in lung and kidney. whereas concentrations in fat are considerably lower than in plasma.Body fluid penetration is introduced as a new approach to evaluate distribution kinetics of quinolones. With the exception of those in nasal secretions and ejaculate. body flUid levels of these drugs rarely reach plasma levels. The body fluid penetration model allows for d{f!erentiation among individual agents. There is no apparent relationship between d{f!erences in body fluid penetration of quinolones and d{f!erences in volume of distribution. For the clinical use of these drugs it is important that the concentrations achieved in body fluids and tissues are sufficient to kill most pathogens. A discussion on the relationship between plasma and tissue levels and the MICs of quinolones is. however. beyond the scope of this article.

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Diffusion of ofloxacin into the cerebrospinal fluid in patients with bacterial meningitis

Cited by 27 publications

References 3 publications

Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally

Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally

Clinical Pharmacokinetics of the Newer Antibacterial 4-Quinolones

Pharmacokinetic Disposition of Quinolones in Human Body Fluids and Tissues

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