Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy

Gaillard, J; Abadie, Véronique; Chéron, G.; Lacaille, Florence; Mahut, Bruno; Silly, C; Matha, V; Coustere, C; Lokiec, François

doi:10.1128/aac.38.5.1209

Cited by 48 publications

(12 citation statements)

References 16 publications

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“…CROi thus represents a strain at the breakpoint between intermediate and full resistance. The concentration of ceftriaxone in CSF varied widely, from 0.9 to 30 g/ml, confirming previous reports (5,10). We found a 2-to 3-log reduction in concentrations of the CROi strain when the level of ceftriaxone in CSF was Ͼ5 g/ml.…”

Section: Discussionsupporting

confidence: 76%

Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis

Klugman

Friedland

Bradley

1995

Antimicrob Agents Chemother

219

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There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extendedspectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n ‫؍‬ 11), ceftriaxone plus rifampin (n ‫؍‬ 10), or ceftriaxone plus vancomycin (n ‫؍‬ 10). The CSF from children receiving ceftriaxone alone was unable to kill intermediately ceftriaxone-resistant or fully resistant strains when the concentration of ceftriaxone in the CSF was less than 5 g/ml. At higher concentrations bactericidal activity was present. We have shown that vancomycin penetrates reliably into the CSF of children with acute meningitis, which is in contrast to previous studies with adults. The addition of vancomycin or rifampin to ceftriaxone resulted in significantly enhanced CSF bactericidal activity compared with that of ceftriaxone alone against these resistant strains. Our data suggest that the addition of rifampin or vancomycin to ceftriaxone may be useful for the treatment of cephalosporin-resistant pneumococcal meningitis.The extended-spectrum cephalosporins cefotaxime and ceftriaxone are widely used as empiric therapy for acute bacterial meningitis in children (4).In 1991, Bradley and Connor (3) described the failure of ceftriaxone therapy to sterilize the cerebrospinal fluid (CSF) of a child infected with a pneumococcus (ceftriaxone MIC of 2 g/ml). A number of subsequent reports (11, 16) have led to a revision in the breakpoint for pneumococcal resistance to cefotaxime and ceftriaxone (12). Currently the addition of vancomycin or rifampin to a cephalosporin is recommended for treatment of pneumococcal meningitis. These recommendations are based on animal studies and in vitro data (7).When rabbits are given doses of extended-spectrum cephalosporins that reach levels in CSF similar to those found in humans, resistant strains are not killed (8). Both in vitro and in the rabbit meningitis model, the addition of vancomycin results in a synergistic bactericidal effect (7). Recent data, however, from the rabbit meningitis model suggest that the coadministration of dexamethasone, now widely used for children with meningitis (1), reduces CSF penetration by vancomycin and abolishes the synergistic effect of the combination of ceftriaxone with vancomycin (14).The objectives of the present study were (i) to measure the penetration of ceftriaxone, rifampin, and vancomycin into the CSF of children with meningitis who were receiving dexamethasone therapy, (ii) to determine the ability of the children's CSF to kill pneumococci resistant to extended-spectrum cephalosporins, and (iii) to assess the impact of the coadministration of vancomycin or rifampin with ceftriaxone on the killing activity of the CSF. MATERIALS AND METHODSChildren Յ5 years of age presenting with signs and symptoms of acute ba...

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Section: Discussionsupporting

confidence: 76%

Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis

Klugman

Friedland

Bradley

1995

Antimicrob Agents Chemother

219

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“…Determination in CSF is less frequent [7,11,12], and even less frequent is the determination of the stability of ceftriaxone in water and biological fluids [13,14].…”

Section: Introductionmentioning

confidence: 99%

Stability of ceftriaxone in water and cerebrospinal fluid determined by high‐performance liquid chromatography

Glaría¹,

Moscciati

Ramos

et al. 2003

J of Separation Science

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Stability of ceftriaxone in water and cerebrospinal fluid determined by high-performance liquid chromatographyA study of the stability of ceftriaxone in water and cerebrospinal fluid in the presence or the absence of buffer at different storage temperatures was performed by liquid chromatography on a C 18 column (12564 mm, 5 lm) using a mobile phase consisting of acetonitrile (300 mL), 0.1 M phosphate buffer (pH 7.4; 50 mL), tetrabutylammonium bromide (3.2 g) made up to a volume of 1 L with water. Detection was at 270 nm with a 50 lL loop and 1 mL/min flow. The study was performed with an without 0.05 M phosphate buffer (pH 6.0) and at room temperature (25 l 28C), +88C, -208C, and -408C, over 15 days, 78 days, and 111 days ( -208C and -408C), respectively. At all the temperatures studied, the degradation of ceftriaxone followed first-order kinetics. Degradation of the drug was greater at higher temperatures and in the absence of phosphate buffer. Lower storage temperatures and the presence of 0.05 M phosphate buffer (pH 6.0) therefore improved the stability of ceftriaxone in water and cerebrospinal fluid.

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“…However, most of those studies were performed with subjects with normal or moderately inflamed meninges. Dexamethasone was given to all our patients as an adjunct agent and appeared to have no or little effect on the penetration of amikacin into the CSF on day 1 of treatment, as recently reported for ceftriaxone (10).…”

mentioning

confidence: 99%

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

Gaillard

Silly

Masne

et al. 1995

Antimicrob Agents Chemother

Self Cite

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The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of <1, 1 to 2, and >2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is <1 mmol/liter on admission.

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Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy

Cited by 48 publications

References 16 publications

Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis

Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis

Stability of ceftriaxone in water and cerebrospinal fluid determined by high‐performance liquid chromatography

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

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