Randomised Comparison of Chloramphenicol, Ampicillin, Cefotaxime, and Ceftriaxone for Childhood Bacterial Meningitis

Peltola, Heikki; Anttila, Marja; Renkonen, Olli-Veikko

doi:10.1016/s0140-6736(89)92685-8

Cited by 157 publications

(69 citation statements)

References 36 publications

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“…Although the long persistence of both ceftriaxone and cefotaxime in CSF would permit long dosage intervals, the rapid elimination of cefotaxime in blood suggests distances between the single infusions of not more than 8 h with meningitis. The lack of a decisive advantage of one drug when they were compared with each other under the conditions studied by us is paralleled by clinical studies of bacterial meningitis and Lyme disease in which they were equally effective (12,29,32).…”

Section: Discussionmentioning

confidence: 95%

“…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.…”

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confidence: 99%

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

Nau

Prange

Muth

et al. 1993

Antimicrob Agents Chemother

125

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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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Section: Discussionmentioning

confidence: 95%

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

125

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“…On the other hand, chloramphenicol concentrations were lower than desired; however, this is also a common problem in treating humans with chloramphenicol. In one report of S. typhimurium meningitis, a dose of 390 mg of chloramphenicol per kg/day was required to achieve concentrations in serum of 20 to 25 ,g/ml (13 24 h for therapy of meningitis in most instances (7,29,37).…”

Section: Discussionmentioning

confidence: 99%

Therapy of experimental meningitis due to Salmonella enteritidis

Bryan

Scheld

1992

Antimicrob Agents Chemother

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In many areas of the developing world, Salmonella spp. account for greater than 50% of the gram-negative enteric organisms isolated from cerebrospinal fluid (CSF). The response of Salmonella meningitis to conventional therapy (chloramphenicol and/or ampicillin) is slow, complications arise frequently, and mortality rates of 60 to 80% are common. Two newer agents, ceftriaxone and imipenem, were compared with ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (TMP-SMX) in the therapy of experimental Salmonella meningitis beginning 14 h after intracisternal inoculation and continued by constant intravenous infusion for 8 h. Drug concentrations in serum and CSF closely approximated those achieved in the sera and CSF of humans receiving standard parenteral regimens. Penetration into purulent CSF [(concentration of drug in CSF/concentration of drug in serum) x 100] ranged from 18 to 41%. The rate of bacterial killing in CSF was significantly (P less than 0.001) more rapid during therapy with ceftriaxone and imipenem than it was during therapy with chloramphenicol or TMP-SMX. Ceftriaxone and imipenem sterilized the CSF of six of seven animals at 8 h, whereas it sterilized the CSF of three of eight animals treated with ampicillin (P = 0.18), one of eight animals treated with chloramphenicol, and none of seven animals treated with TMP-SMX (P less than or equal to 0.01; ceftriaxone or imipenem versus chloramphenicol or TMP-SMX). New beta-lactams, including ceftriaxone and imipenem, appear to be effective therapy against Salmonella spp. in this animal model and deserve further evaluation in humans.

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“…In patients with H. influenzae type b meningitis, the emergence of b-lactamase-producing strains and resistance to chloramphenicol has made these agents the drugs of choice for empirical therapy for H. influenzae meningitis, pending results of in vitro susceptibility testing. In clinical trials, the third-generation cephalosporins have been found to be superior to chloramphenicol and cefuroxime (a secondgeneration cephalosporin) and are recommended for the treatment of childhood bacterial meningitis [36,78,79] (A-I). In patients with pneumococcal and meningococcal meningitis, the third-generation cephalosporins are recommended in patients with meningitis caused by strains that are not susceptible to penicillin (MIC, у0.1 mg/mL) [1,80,81] (A-III).…”

Section: Once the Bacterial Etiology Of Meningitis Is Established Whmentioning

confidence: 99%

Pneumococcal Meningitis Successfully Treated with Adjuvant Management of Intrathecal Vancomycin, Oral Rifampicin and Shunt Surgery

Yim

Kim

2016

J Neurocrit Care

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OBJECTIVESThe objective of these practice guidelines is to provide clinicians with recommendations for the diagnosis and treatment of bacterial meningitis. Patients with bacterial meningitis are usually treated by primary care and emergency medicine physicians at the time of initial presentation, often in consultation with infectious diseases specialists, neurologists, and neurosurgeons. In contrast to many other infectious diseases, the antimicrobial therapy for bacterial meningitis is not always based on randomized, prospective, double-blind clinical trials, but rather on data initially obtained from experimental animal models of infections. A model commonly utilized is the experimental rabbit model, in which animals are anesthetized and placed in a stereotactic frame. In this procedure, the cisterna magna can be punctured for frequent sampling of CSF and injection of microorganisms. Frequent sampling of CSF permits measurement of leukocytes and chemical parameters and quantitation of the relative penetration of antimicrobial agents into CSF and the effects of meningitis on this entry parameter, the relative bactericidal efficacy (defined as the rate of bacterial eradication) within purulent CSF, and CSF pharmacodynamics. Results obtained from these and other animal models have led to clinical trials of specific agents in patients with bacterial meningitis.

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Randomised Comparison of Chloramphenicol, Ampicillin, Cefotaxime, and Ceftriaxone for Childhood Bacterial Meningitis

Cited by 157 publications

References 36 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

Therapy of experimental meningitis due to Salmonella enteritidis

Pneumococcal Meningitis Successfully Treated with Adjuvant Management of Intrathecal Vancomycin, Oral Rifampicin and Shunt Surgery

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