Pharmacokinetics and bacteriological efficacy of mezlocillin in experimental Escherichia coli and Listeria monocytogenes meningitis

C. Odio, M. L. Thomas, G. H. McCracken

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Abstract

The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were <1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of <1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56°C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume25
Issue number4
StatePublished - 1984

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Listeria Meningitis
Mezlocillin
Pharmacokinetics
Escherichia coli
Cerebrospinal Fluid
Serum
Listeria monocytogenes
Listeriosis
Ampicillin
Heating
Bacillus
Half-Life

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

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title = "Pharmacokinetics and bacteriological efficacy of mezlocillin in experimental Escherichia coli and Listeria monocytogenes meningitis",
abstract = "The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15{\%} after a single dose and 5 to 20{\%} after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were <1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony of susceptible E. coli in CSF by 90{\%} or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of <1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56°C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.",
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T1 - Pharmacokinetics and bacteriological efficacy of mezlocillin in experimental Escherichia coli and Listeria monocytogenes meningitis

AU - Odio, C.

AU - Thomas, M. L.

AU - McCracken, G. H.

PY - 1984

Y1 - 1984

N2 - The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were <1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of <1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56°C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.

AB - The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were <1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of <1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56°C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.

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