A Comparison of Ceftriaxone and Cefuroxime for the Treatment of Bacterial Meningitis in Children

Schaad, Urs B.; Suter, Susanne; Gianella‐Borradori, Athos; Pfenninger, J.; Auckenthaler, Raymond; Bernath, Otto; Cheseaux, Jean‐Jacques; Wedgwood, Joanna

doi:10.1056/nejm199001183220301

Cited by 227 publications

(95 citation statements)

References 22 publications

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“…The emergence of bacteria not susceptible to standard antibacterial agents in meningitis of children and immunocompromised adults has stimulated the search for alternative drugs. Broad-spectrum cephalosporins have a broad range of in vitro antibacterial activities, including that against most organisms responsible for purulent meningitis (6,7,19), and have been successfully applied as single agents for this indication in children and adults (3,9,29,34,37 Two grams of cefotaxime (Claforan; Hoechst AG, Frankfurt/M, Germany) or 2 g of ceftriaxone (Rocephin; Hoffmann-La Roche, Grenzach-Wyhlen, Germany) was infused intravenously within 30 min. Single-dose pharmacokinetics were determined after the first infusion for six patients receiving cefotaxime and six patients receiving ceftriaxone.…”

mentioning

confidence: 99%

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Nau

Prange

Muth

et al. 1993

Antimicrob Agents Chemother

126

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Cefotaxime and ceftriaxone have proven to be effective in pyogenic infections of the central nervous system. Since in some bacterial central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both antibiotics in the absence of inflamed meninges. Patients who had undergone external ventriculostomies for noninflammatory occlusive hydrocephalus received either cefotaxime (2 g/30 min) or ceftriaxone (2 g/30 min) to treat extracerebral infections. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrations of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of cefotaxime and ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and penicillin G-resistant Streptococcus pneumoniae.Because of its morbidity and lethality, bacterial meningitis remains a major medical concern throughout the world. The emergence of bacteria not susceptible to standard antibacterial agents in meningitis of children and immunocompromised adults has stimulated the search for alternative drugs. Broad-spectrum cephalosporins have a broad range of in vitro antibacterial activities, including that against most organisms responsible for purulent meningitis (6,7,19), and have been successfully applied as single agents for this indication in children and adults (3,9,29,34,37 Two grams of cefotaxime (Claforan; Hoechst AG, Frankfurt/M, Germany) or 2 g of ceftriaxone (Rocephin; Hoffmann-La Roche, Grenzach-Wyhlen, Germany) was infused intravenously within 30 min. Single-dose pharmacokinetics were determined after the first infusion for six patients receiving cefotaxime and six patients receiving ceftriaxone. To obtain a 24-h time course with cefotaxime, the second infusion was administered 24 h after the first dose. Thereafter, therapy was continued with 2 g three times a day or twice a day. For this reason, patients with pneumonia or fever greater than 38.5°C during the 24-h interval before the

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mentioning

confidence: 99%

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Nau

Prange

Muth

et al. 1993

Antimicrob Agents Chemother

126

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“…Intravenous penicillin-G is the drug of choice and 4 mega units every four hours were administered to all patients. Third generation cephalosporins have been used successfully in the treatment of meningococcal meningitis [12,13] and they are useful alternative antibiotics in place of penicillin. Two patients received intravenous cefotaxime, as they were sensitive to penicillins.…”

Section: Discussionmentioning

confidence: 99%

Meningococcal Disease: Clinical Profile of 99 Patients

Barlas

Chaudhry

et al. 1993

Ann Saudi Med

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“…This may be an important factor since there is some evidence that cefuroxime is inferior to ceftriaxone for treating bacterial meningitis. In one prospective evaluation, two of six children treated with cefuroxime vs. none of seven children receiving ceftriaxone for pneumococcal meningitis developed a hearing impairment [25].…”

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confidence: 99%

Steroid Therapy for Bacterial Meningitis

Schaad

Kaplan

McCracken

1995

Clinical Infectious Diseases

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Routine dexamethasone therapy for bacterial meningitis in pediatric patients is controversial. Two experts debated this topic at the 1993 meeting of the Infectious Diseases Society of America. Both experts agreed that for management of Haemophilus influenzae meningitis, dexamethasone significantly reduced sensorineural hearing loss and probably reduced other long-term sequelae. Because relatively few patients with pneumococcal and meningococcal meningitis have been studied, no conclusions could be reached regarding the effectiveness of dexamethasone. Dr. Urs Schaad emphasized the impressive anti-inflammatory effects of dexamethasone in experimental pneumococcal meningitis and the lack of any adverse events when given to children for 2 or 4 days. He recommended routine use of dexamethasone in treating pediatric patients with bacterial meningitis. Dr. Sheldon Kaplan expressed concern regarding the effectiveness of steroids in treating pneumococcal meningitis, especially when penicillin-resistant and cephalosporin-resistant isolates are present, and he addressed the question of the long-term effects of administration of dexamethasone in children with viral meningitis. He advised against the routine use of dexamethasone for non-H. influenzae meningitis.At the annual meeting of the Infectious Diseases Society of America in October 1993, one of the sessions was devoted to the controversy of whether dexamethasone should be routinely used to treat patients with bacterial meningitis. The two physicians chosen to address this issue had recently conducted multicenter, placebo-controlled, double-blind studies of dexamethasone therapy in children with meningitis. Dr. Urs B. Schaad was asked to present information supporting the routine use of dexamethasone therapy in these patients. Dr. Sheldon L. Kaplan took the opposing view-that dexamethasone should be used only in select patients with bacterial meningitis. The following paper represents a distillation of their presentations and a commentary by Dr. George H. McCracken, Jr. Affirmative ViewBacterial meningitis remains an important cause of death and permanent neurological disability despite advances in antimicrobial therapy, rapid diagnostic techniques, and sup- Data from recent in vitro and animal experiments indicate that the bacteria causing meningitis elaborate outer membrane-active or cell wall-active components that affect monocytes, leukocytes, cerebrovascular endothelial cells, and astrocytes [1][2][3]. These cells, in turn, produce various proinflammatory cytokines or express specific receptors on their surface. These cytokines and receptors initiate an accelerating cascade of events, resulting in alteration of the bloodbrain barrier, meningeal inflammation, increased intracranial pressure, and decreased cerebral vascular perfusion. If the interaction of these pathopysiological alterations is severe and sustained, it will produce neuronal injury and irreversible focal or diffuse brain damage.Dexamethasone is a potent antiinflammatory agent. There is convincing in ...

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A Comparison of Ceftriaxone and Cefuroxime for the Treatment of Bacterial Meningitis in Children

Cited by 227 publications

References 22 publications

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges

Meningococcal Disease: Clinical Profile of 99 Patients

Steroid Therapy for Bacterial Meningitis

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