Therapeutic studies of cefepime (BMY 28142) in murine meningitis and pharmacokinetics in neonatal rats

Tsai, Yuan-Hwang; Bies, M; Leitner, F.; Kessler, R E

doi:10.1128/aac.34.5.733

Cited by 25 publications

(23 citation statements)

References 19 publications

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“…The results indicated that cefepime penetrated paralysed, as well as normal, soft tissue in mice. Penetration into cerebrospinal fluid and brain tissue in rabbits and neonatal rats was greater with cefepime than cefotaxime (Tauber et al 1985;Tsai et al 1990). The bactericidal activity of cefepime in animals with induced meningitis was comparable with that of cefotaxime against Streptococcus pneumoniae, S. aureus, H. injluenzae, E. coli and group B streptococci (Kim & Bayer 1985;Tauber et al 1985;Tsai et al 1990).…”

Section: Animal Modelsmentioning

confidence: 96%

“…Penetration into cerebrospinal fluid and brain tissue in rabbits and neonatal rats was greater with cefepime than cefotaxime (Tauber et al 1985;Tsai et al 1990). The bactericidal activity of cefepime in animals with induced meningitis was comparable with that of cefotaxime against Streptococcus pneumoniae, S. aureus, H. injluenzae, E. coli and group B streptococci (Kim & Bayer 1985;Tauber et al 1985;Tsai et al 1990). Preliminary studies with mice have found that cefepime is superior to ceftazidime in eradicating E. coli-and P. aeruginosa-induced bacteraemia (Tomatsu et al 1986;Van Ogtrop et al 1990).…”

Section: Animal Modelsmentioning

confidence: 96%

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Cefepime Clinical Pharmacokinetics

Okamoto

Nakahiro

Chin

et al. 1993

Clinical Pharmacokinetics

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Cefepime is a new parenteral cephalosporin with antimicrobial activity similar to third-generation cephalosporins. It acts against the Enterobacteriaceae family, and Pseudomonas aeruginosa, but maintains Gram-positive activity similar to that of first- or second-generation cephalosporins. Cefepime has in vitro activity against many bacterial isolates resistant to ceftazidime and cefotaxime, is stable against chromosomally mediated beta-lactamases, demonstrates lower affinity for these enzymes and shows a high resistance to enzymatic hydrolysis. Clinical uses thus far include treatment of lower respiratory tract, intra-abdominal and urinary tract infections, skin and soft tissue infections and for prophylaxis in biliary tract and prostate surgery. Pharmacokinetic studies indicate that cefepime exhibits linear pharmacokinetic behaviour. Pharmacokinetic variables are not significantly different between single- and multiple-dose administration, indicating a lack of drug accumulation in patients with normal renal function. Cefepime is not highly bound to plasma proteins, with binding values of approximately 16 to 19%. The drug is widely distributed in various biological tissues and fluids. The primary route of elimination is from the kidneys, with over 80% of the drug recovered in the urine as unchanged drug in patients with normal renal function. Total drug clearance and renal clearance are similar to creatinine clearance, and glomerular filtration is thought to be the primary mechanism of renal excretion. The elimination half-life is approximately 2 to 2.5 h in patients. Cefepime is removed by haemodialysis (over 3h) and peritoneal dialysis (over 72h) to an appreciable extent, with 40 to 68% and 26% of the drug removed, respectively. Overall, cefepime is well tolerated by patients and no significant drug interactions have been reported to date.

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Section: Animal Modelsmentioning

confidence: 96%

Section: Animal Modelsmentioning

confidence: 96%

Cefepime Clinical Pharmacokinetics

Okamoto

Nakahiro

Chin

et al. 1993

Clinical Pharmacokinetics

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“…Cefepime is a fourth-generation cephalosporin with a broad antimicrobial spectrum that was found to be effective in experimental animal models against a variety of meningeal pathogens, including S. pneumoniae, S. agalactiae, E. coli, K. pneumoniae, and P. aeruginosae [59,60]. The MIC90 for P. aeruginosa is higher than that of ceftazidime, but lower than those of cefpirome and cefoperazone [61].…”

Section: Cefepimementioning

confidence: 98%

Treatment of bacterial meningitis: an update

Shin

Kim

2012

Expert Opinion on Pharmacotherapy

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Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.

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“…The rat has also been exploited for studying invasive pneumococcal disease and otitis media. Outbred strains, including Wistar, Sprague-Dawley, and CD (derived from Sprague-Dawley) rats, have been extensively utilized as experimental models (2,49,71,79,101,103,145,147,166,193,214,221,242,253). The New Zealand White rabbit is the most commonly used strain to induce pneumococcal pneumonia, sepsis, and meningitis (26,57,69,98,106,119,196,246).…”

Section: Considerations Of Animal and Pneumococcal Strainsmentioning

confidence: 99%

“…infant rat meningitis model was used by different groups, mainly for therapeutic studies (242,259). In 1990, Tsai et al established an important i.cist.…”

Section: Rat and Rabbit Modelsmentioning

confidence: 99%

Animal Models ofStreptococcus pneumoniaeDisease

2008

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SUMMARY Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.

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Therapeutic studies of cefepime (BMY 28142) in murine meningitis and pharmacokinetics in neonatal rats

Cited by 25 publications

References 19 publications

Cefepime Clinical Pharmacokinetics

Cefepime Clinical Pharmacokinetics

Treatment of bacterial meningitis: an update

Animal Models ofStreptococcus pneumoniaeDisease

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