Pneumococcal Meningitis-Therapeutic Studies in Mice

Tsai, Yuan-Hwang; Williams, E.B.; Hirth, R. S.; Price, K. E.

doi:10.1159/000221879

Cited by 19 publications

(12 citation statements)

References 24 publications

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“…Previous reports have described clinical and histopathological manifestations of neonatal murine meningitis (13,14) and pneumococcal meningitis in adult mice (15) and one report demonstrated significant CSF leukocyte influx at 48 h using Listeria monocytogenes or lymphocytic choriomeningitis virus (16). However, to our knowledge, rapid CSF leukocyte accumulation and injury to the BBB have not been described previously in adult mice.…”

Section: Introductionmentioning

confidence: 99%

Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins.

et al. 1996

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Leukocyte accumulation in cerebrospinal fluid and disruption of the blood-brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P-plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal inflammation has not been tested previously. An acute cytokine-induced meningitis model associated with significant cerebrospinal fluid leukocyte accumulation (averaging 14,000 leukocytes/ l as early as 4 h) and blood-brain barrier permeability was developed in adult mice. This model was applied to mice deficient in P-selectin and mice doubly deficient in P-and E-selectins. Partial inhibition of cerebrospinal fluid leukocyte influx and permeability was noted in P-selectin-deficient mice. Mice doubly deficient in P-and E-selectins displayed a near complete inhibition of these parameters. Our results suggest that P-and E-selectins cooperatively contribute to meningitis and that functional

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Section: Introductionmentioning

confidence: 99%

Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins.

et al. 1996

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“…The 75 bacterial strains used in this study (see Table 1) were mainly from our culture collection but also included some recent clinical isolates obtained from several hospital sources. The six group B streptococcus strains were Streptococcus agalactiae from our culture collection and types Ia-090, Ib-H36B, Ic (15), who described the histopathological changes that accompany this experimentally produced disease. The mice, under light Metofane anesthesia, were injected intracraniaUy through the right orbital surface of the zygomatic bone (posterior corner of the right eye) with 0.03 ml of an infecting inoculum containing 100 to 1,000 LD50s.…”

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confidence: 99%

“…Plasma levels of ceftriaxone and cefotaxime were determined at various times after intravenous administration of 50 mg of either antibiotic per ml dissolved in physiological saline. Blood samples were taken at each of the indicated time intervals (5,10,15,20,30,60,120, and 240 min) by cardiac puncture with a heparinized syringe. The samples from five mice were pooled and centrifuged immediately.…”

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confidence: 99%

In vivo activity of ceftriaxone (Ro 13-9904), a new broad-spectrum semisynthetic cephalosporin

Beskid¹,

Christenson²,

Cleeland³

et al. 1981

Antimicrob Agents Chemother

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Ceftriaxone (Ro 13-9904) was compared with other newer f3-lactam antibiotics for activity in experimental infections of mice with Enterobacteriaceae, Haemophilu influenzae, Pseudomonas aeruginosa, and gram-positive bacteria. Overall, ceftriaxone was equal or superior to cefotaxime and cefoperazone against systemic infections. All three drugs were highly potent against most organisms but were considerably less active against P. aeruginosa. However, ceftriaxone tended to be more active ihan the other two agents against 8 of the 10 P. aeruginosa strains tested. Ceftriaxone, cefmenoxime (SCE 1365), and moxalactam were all highly active against systemic infections with 16 strains of Enterobacteriaceae, whereas ceftriaxone was more active against infections with two strains of streptococci. When the drugs were administered at various time intervals before infection, ceftriaxone was superior to cefotaxime, cefmenoxime, and moxalactam. This suggested that ceftriaxone might be eliminated from mice more slowly than the other drugs. In the case of cefotaxime, this was directly confirmed by microbiological assays of plasma samples. In a murine meningitis model induced by Klebsiella penumoniae or Streptococcus pneumoniae, ceftriaxone was more active than ampicillin or cefotaxime. Ceftriaxone was more active than ampicillin, cefotaxime, piperacillin, cefamandole, or carbenicillin in a pneumococcal pneumonia model in mice. These studies indicate that ceftriaxone is a potent, broadspectrum cephalosporin with unusual pharmacokinetic properties.Ceftriaxone (Ro 13-9904), a 2-aminothiazolyl methoxyimino cephalosporin derivative, has exhibited high orders of activity, both in vitro (1,2,5,7,11,13,14,17, 18)

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“…Because of in vitro potency against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis that is equal to that of ampicillin (10), amoxicilhin should be equally as effective as ampicillin in bacterial meningitis. Studies in aniimal models of infection support this assertion (4,18).…”

mentioning

confidence: 96%

Treatment of Bacterial Meningitis with Intravenous Amoxicillin

Nolan¹,

Chalhub²,

Nash

et al. 1979

Antimicrob Agents Chemother

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Eleven children with bacterial meningitis were treated intravenously with amoxicillin sodium to evaluate the efficacy of the parenteral form of amoxicilhin for this serious infection and to measure the penetration of the drug into cerebrospinal fluid (CSF). The infecting organisms were Haemophilus influenzae in nine cases and Streptococcus pneumoniae in two. Nine patients had optimal responses to amoxicillin sodium, 200 mg/kg per day for 14 days. Bacteria were also eradicated from CSF of the other two, but one experienced fever and culturenegative CSF pleocytosis after cessation of amoxicilhin, and the other developed H. influenzae empyema 2 weeks after termination of therapy. By comparison, 7 of 10 children with meningitis responded optimally to ampicillin (nonrandomized design) during the period of study. The mean peak CSF concentration of amoxicillin was 3.14 ,ug/ml (ca. 7% of the concomitant mean peak serum level) early during therapy. However, meningeal penetration of the drug declined to a mean peak of 0.63 ,ug/ml on the final day of therapy. Mild transient neutropenia, noted in five patients, was the most common side effect of amoxicillin sodium therapy; five patients treated with ampicillin also experienced reversible neutropenia. Thus, intravenous amoxicillin sodium provided therapy for bacterial meningitis comparable to that of ampicillin in this limited case-control study.Ampicillin has provided safe and effective therapy for bacterial illnesses of children, including most cases of bacterial meningitis, for 15 years (1, 19). Amoxicilhin, a congener of ampicillin differing from the parent drug only by hydroxylation of the phenyl side chain, has recently found a niche in the treatment of ampicillin-responsive infections because it is better absorbed after oral administration (7, 10). A parenteral preparation of amoxicilhin has now been developed. Because of in vitro potency against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis that is equal to that of ampicillin (10), amoxicilhin should be equally as effective as ampicillin in bacterial meningitis. Studies in aniimal models of infection support this assertion (4, 18).The present study was designed to obtain preliminary infornation on the clinical use of the parenteral form of amoxicilhin in bacterial meningitis in children. A small number of patients were treated under carefully controlled circumstances, and the diffusion of the drug into cerebrospinal fluid (CSF) was measured.t Present addres:

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Pneumococcal Meningitis-Therapeutic Studies in Mice

Cited by 19 publications

References 24 publications

Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins.

Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins.

In vivo activity of ceftriaxone (Ro 13-9904), a new broad-spectrum semisynthetic cephalosporin

Treatment of Bacterial Meningitis with Intravenous Amoxicillin

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