Therapy of experimental meningitis due to Salmonella enteritidis

Abstract

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.

The outcome of non-typhoidal salmonella meningitis in Malawian children, 1997–2006

“…15 In experimental animal models of S. enteritidis meningitis, ceftriaxone sterilised the CSF in six of seven animals in 8 hours, compared with three of eight for ampicillin, one of eight for chloramphenicol and none with cotrimoxazole. 13 In Rwanda, among 199 patients requiring hospitalisation for multi-resistant salmonella infections, 10.5% who received ceftriaxone died compared with 64% who received alternative antibiotics; 24 only 12 of these patients had meningitis. Price et al noted that antibiotic regimens for salmonella meningitis have not been very successful and that the mortality rate with chloramphenicol treatment, with or without ampicillin, in several studies in well resourced centres is ,30%.…”

“…[13][14][15] For these reasons, various authors have recommended the use of third-generation cephalosporins in the management of salmonella meningitis. [13][14][15] Because of frequent recurrences of invasive salmonella disease, further recommendations have included lengthening the treatment beyond 10 days and the addition of a quinolone. To date there has been no study demonstrating the superiority of these approaches to the treatment of salmonella meningitis in an African paediatric population.…”

Oral infection of mice with Salmonella entericaserovar Typhimurium causes meningitis and infection of the brain

“…Lack of an appropriate animal model has made it difficult to address these questions. An animal model in rabbits of experimental S. enterica serotype Enteriditis meningitis has been reported [15], although this model involved direct inoculation of the cerebral spinal fluid using an intracisternally placed needle. Currently there is a dearth of reports that describe the natural progression of salmonellosis from the intestinal mucosa, though the CNS and to the brain.…”

Extended-Spectrum-Cephalosporin Resistance in Salmonella enterica Isolates of Animal Origin

“…Extended-spectrum cephalosporins such as ceftriaxone and ceftiofur are important therapeutic agents and are often used for invasive Salmonella infections (4,6). The emergence of Salmonella isolates that are resistant to extended-spectrum cephalosporins has been reported (7,8,14,18).…”