Susceptibility testing methods: why use the MIC?
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Biomedical subjects
Publications and source records attributed to P Silley.
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The administration of a single dose of the antibacterial agent cephalexin intramuscularly to six ponies at a dose rate of 7 mg/kg was well tolerated. No reactions at the injection site were apparent. It was absorbed rapidly and reached a mean peak plasma concentration of 6.77 micrograms/ml after a mean of 1.41 hours; plasma concentrations above 2.0 and 0.5 micrograms/ml were maintained for 3.8 and 9.8 hours, respectively.
An in-vitro model was shown to be capable of simulating a cefuroxime serum profile equivalent to that observed in human volunteer studies, following a single dose of 250 mg cefuroxime axetil. The model was used to carry out kill kinetic studies and showed cefuroxime to lyse the four bacterial test strains, time of onset of lysis being related to the sensitivity of the respective organisms. The more sensitive Staphylococcus aureus and Haemophilus influenzae strains were subject to a higher absolute kill and showed no regrowth over the duration of the simulated serum profile. In contrast, Proteus mirabilis and Escherichia coli showed regrowth after 4 and 5 h respectively. The kill kinetic profiles of the respective organisms are discussed in relation to the pharmacokinetic analysis of the cefuroxime serum profile.
GR69153 is a novel cephalosporin incorporating a catechol-substituted 7-aminothiazolyl-oxime. The antibiotic is actively transported into gram-negative cells via iron-regulated outer membrane proteins regulated by the tonB product. This transport enhances bactericidal activity most significantly at low concentrations, essentially removing the permeability barrier for antibiotic uptake.
Kill kinetic studies for two cephalosporin antibiotics, cephalexin and cefuroxime were carried out against veterinary strains of Escherichia coli, Pasteurella multocida, Streptococcus suis, Erysipelothrix rhusiopathiae and a laboratory culture of Staphylococcus aureus. In more than 90 per cent of cases a kill of more than 99 per cent was achieved within four hours of antibiotic treatment at concentrations of 2 or 4 micrograms/ml. Although cefuroxime was effective at lower concentrations than cephalexin the rates of kill of the two antibiotics were comparable. The results are discussed in relation to in vivo dosage regimens.
A three-way crossover study was carried out in 10 dogs and nine cats to establish the pharmacokinetic parameters of the semi-synthetic cephalosporin antibiotic, cephalexin sodium, when administered orally, subcutaneously or intramuscularly. Ten dogs received a subcutaneous or intramuscular injection of 10 mg/kg bodyweight cephalexin or an oral dose of three 50 mg cephalexin tablets; the peak serum concentrations achieved were 24.9, 31.9 and 18.6 micrograms/ml, respectively, and the times taken to reach these peak levels were 1.2, 0.9 and 1.8 hours. Nine cats received either a subcutaneous or intramuscular dose of 0.25 ml cephalexin suspension (approximately 20 mg/kg bodyweight) or an oral dose of one 50 mg tablet; the peak serum concentrations achieved were 54.0, 61.8 and 18.7 micrograms/ml for the subcutaneous, intramuscular and oral administrations respectively, with times to peak concentrations of 1.1, 0.7 and 2.6 hours.
Initial metabolism of Selenomonas ruminantium 0078A in continuous culture was characterized by a high lactate and low volatile fatty acid production; this was associated with poor growth as determined by bacterial dry weight production, yet individual cells were considerably larger than those of the inoculum. Biomass production increased, cell size decreased and the fermentation pattern reverted to the characteristic low lactate and high volatile fatty acid production after approximately 90 h growth.
Streptococcus bovis H13/1 was grown in a glucose-limited chemostat. A concomitant increase in dilution rate and glucose supply per unit time caused both an increase in lactate production per mole of glucose fermented and a linear increase in growth yield over the dilution rate range 0.052 to 0.141/h. When the dilution rate was increased with no change in glucose supply per unit time there was a reduction in lactate production and an increase in that of acetate and ethanol coinciding with a non-linear increase in growth yield. YMaxglu = 38.6 and a maintenance coefficient, ms = 0.290 mmol/l glucose/g cells/h were calculated. The results also suggested an interaction between the formate and CO2 pools.