Once-daily gentamicin therapy for experimental Escherichia coli meningitis

Amina Ahmed, María M. París, Mónica Trujillo, Sheila M. Hickey, Loretta Wubbel, Sharon L. Shelton, George H. McCracken

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Abstract

In vitro and in vivo studies have demonstrated that the bacteriologic efficacy of once-daily aminoglycoside therapy is equivalent to that achieved with conventional multiple daily dosing. The impact of once-daily dosing for meningitis has not been studied. Using the well-characterized rabbit meningitis model, we compared two regimens of the same daily dosage of gentamicin given either once or in three divided doses for 24 or 72 h. The initial 1 h mean cerebrospinal fluid (CSF) gentamicin concentration for animals receiving a single dose (2.9 ± 1.7 μg/ml) was threefold higher than that for animals receiving multiple doses. The rate of bacterial killing in the first 8 h of treatment was significantly greater for the animals with higher concentrations in their CSF (-0.21 ± 0.19 versus -0.03 ± 0.22 log10 CFU/ml/h), suggesting concentration-dependent killing. By 24 h, the mean reduction in bacterial titers was similar for the two regimens. In animals treated for 72 h, no differences in bactericidal activity were noted at 24, 48, or 72 h. Gentamicin at two different dosages was administered intracisternally to a separate set of animals to achieve considerably higher CSF gentamicin concentrations. In these animals, the rate of bacterial clearance in the first 8 h (-0.52 ± 0.15 and -0.58 ± 0.14 log10 CFU/ml/h for the lower and higher dosages, respectively) was significantly greater than that in animals treated intravenously. In conclusion, there is evidence of concentration-dependent killing with gentamicin early in treatment for experimental E. coli meningitis, and once-daily dosing therapy appears to be at least as effective as multiple-dose therapy in reducing bacterial counts in CSF.

Original languageEnglish (US)
Pages (from-to)49-53
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume41
Issue number1
StatePublished - Jan 1997

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Escherichia coli Meningitis
Investigational Therapies
Gentamicins
Cerebrospinal Fluid
Meningitis
Bacterial Load
Aminoglycosides
Therapeutics
Rabbits

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Ahmed, A., París, M. M., Trujillo, M., Hickey, S. M., Wubbel, L., Shelton, S. L., & McCracken, G. H. (1997). Once-daily gentamicin therapy for experimental Escherichia coli meningitis. Antimicrobial Agents and Chemotherapy, 41(1), 49-53.

Once-daily gentamicin therapy for experimental Escherichia coli meningitis. / Ahmed, Amina; París, María M.; Trujillo, Mónica; Hickey, Sheila M.; Wubbel, Loretta; Shelton, Sharon L.; McCracken, George H.

In: Antimicrobial Agents and Chemotherapy, Vol. 41, No. 1, 01.1997, p. 49-53.

Research output: Contribution to journalArticle

Ahmed, A, París, MM, Trujillo, M, Hickey, SM, Wubbel, L, Shelton, SL & McCracken, GH 1997, 'Once-daily gentamicin therapy for experimental Escherichia coli meningitis', Antimicrobial Agents and Chemotherapy, vol. 41, no. 1, pp. 49-53.
Ahmed A, París MM, Trujillo M, Hickey SM, Wubbel L, Shelton SL et al. Once-daily gentamicin therapy for experimental Escherichia coli meningitis. Antimicrobial Agents and Chemotherapy. 1997 Jan;41(1):49-53.
Ahmed, Amina ; París, María M. ; Trujillo, Mónica ; Hickey, Sheila M. ; Wubbel, Loretta ; Shelton, Sharon L. ; McCracken, George H. / Once-daily gentamicin therapy for experimental Escherichia coli meningitis. In: Antimicrobial Agents and Chemotherapy. 1997 ; Vol. 41, No. 1. pp. 49-53.
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