Experimental study of the efficacy of vancomycin, rifampicin and dexamethasone in the therapy of pneumococcal meningitis
Laboratory of Experimental Infection, Infectious Diseases Service and Microbiology Service, Ciutat Sanitària i Universitaria de Bellvitge, C.Feixa Larga s/n, 08907 L'Hospitalet, Barcelona, Spain. Journal of Antimicrobial Chemotherapy
(Impact Factor: 5.31).
04/2002; 49(3):507-13. DOI: 10.1093/jac/49.3.507
The object of the study was to assess the efficacy of rifampicin and the combination of rifampicin plus vancomycin in a rabbit model of experimental penicillin-resistant pneumococcal meningitis. We also studied the effect of concomitant dexamethasone on the CSF antibiotic levels and inflammatory parameters. The rabbit model of pneumococcal meningitis was used. Groups of eight rabbits were inoculated with 106 cfu/mL of a cephalosporin-resistant pneumococcal strain (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours later they were treated with rifampicin 15 mg/kg/day, vancomycin 30 mg/kg/day or both plus minus dexamethasone (0.25 mg/kg/day) for 48 h. Serial CSF samples were withdrawn to carry out bacterial counts, antibiotic concentration and inflammatory parameters. Rifampicin and vancomycin promoted a reduction of >3 log cfu/mL at 6 and 24 h, and cfu were below the level of detection at 48 h. Combination therapy with vancomycin plus rifampicin was not synergic but it had similar efficacy to either antibiotic alone and it was able to reduce bacterial concentration below the level of detection at 48 h. Concomitant use of dexamethasone decreased vancomycin levels when it was used alone (P< 0.05), but not when it was used in combination with rifampicin. Rifampicin alone at 15 mg/kg/day produced a rapid bactericidal effect in this model of penicillin-resistant pneumococcal meningitis. The combination of vancomycin and rifampicin, although not synergic, proved to be equally effective. Using this combination in the clinical setting may allow rifampicin administration without emergence of resistance, and possibly concomitant dexamethasone administration without significant interference with CSF vancomycin levels.
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- "Clinical benefit was less evident in cases of pneumococcal meningitis; dexamethasone was most beneficial when given with or shortly before the first dose of parenteral antibiotic therapy . Because dexamethasone can decrease antibiotic penetration into the CNS, concerns have been raised that the use of steroids may impede the eradication of highly resistant pneumococcal strains from the CSF   . Clinical data do not support this hypothesis, however, when the combination of vancomycin and a third-generation cephalosporin is used as initial empirical therapy. "
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ABSTRACT: Microbiologic causes of meningitis include bacteria, viruses, fungi, and parasites. Before routine use of pneumococcal conjugate vaccine, bacterial meningitis affected almost 6000 people every year in the United States, and about half of all cases occurred in children 18 years old or younger. Prompt and accurate diagnosis and adequate treatment of bacterial meningitis in children remains a major challenge, as reflected by the continued high morbidity and case-fatality rates of the disease worldwide. Appropriate use of antibiotics, along with adjunctive therapies, such dexamethasone, has proved helpful in the prevention of neurologic sequelae in children with bacterial meningitis. Better understanding of pathophysiologic mechanisms likely would result in more effective therapies in the future.
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ABSTRACT: Controlled trials concerning adjuvant dexamethasone therapy in bacterial meningitis do not point unequivocally to a beneficial effect on hearing ability. We investigated the remote adverse outcomes of pneumococcal meningitis and, if any, beneficial effects of adjuvant dexamethasone therapy on hearing ability. Fifty-five subjects who experienced pneumococcal meningitis between 1987-97 were divided into two groups as 25 subjects who did not receive dexamethasone (Group 1) and the remaining 30 subjects who did (Group 2). All subjects underwent pure tone thresholds estimation. There were a total of 11 subjects (20%) with sensorineural hearing impairment (SNHI): 6 in the first group (24%) and 5 in the second group (16%). Although there was no statistically significant difference in the SNHI ratio between the groups, all the subjects who used adjuvant dexamethasone therapy suffered only minimal-borderline SNHI, whereas 2 patients in Group 1 had moderate-serious SNHI. Even though adjuvant dexamethasone therapy had no statistically significant impact on hearing ability after long-term follow-up, its use may be a good choice in terms of preventing serious SNHI.
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