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Biomedical subjects

G Carret

Publications and source records attributed to G Carret.

42 records · Page 3Linked to original sources
PubMedDate not supplied

Mathematical modelling of bacterial growth at subinhibitory levels of aminoglycosides.

The subinhibitory effect of antibiotics has often been studied without any clear theoretical framework; we have chosen to use mathematical bacterial growth modelling as a useful tool to analyse these biological states in a more rigorous manner. Since their mode of action and molecular target are relatively well known, aminoglycosides were well suited for this more sophisticated study of subinhibitory action. We have shown that two models (the Monod and the logistic models) regularly used in bacteriology, were adequate to describe these effects in a glucose-limited medium. A change of model, according to antibiotic concentration, revealed the existence of two separate actions. At lower concentrations, inhibition affected mainly glucose use, the substrate remained limiting and growth mode did not change. As soon as the concentration exceeded a threshold, growth was totally disturbed, probably through a physiological "catastrophe". This threshold can be used to estimate bacterial susceptibility to these antibiotics.

Aminoglycosides↗
PubMedDate not supplied

Mathematical modelling of growth of Escherichia coli at subinhibitory levels of chloramphenicol or tetracyclines.

A mathematical model is suggested to describe the subinhibitory effects of chloramphenicol upon growth of Escherichia coli. It represents a generalization of Monod's equation. Our model was constructed entirely on the basis of biochemical factors, such as the reversibility of the interaction between the drug and its ribosomal target or intracellular uptake. The subinhibitory effects of chloramphenicol were satisfactorily described by this law within the range of 0.4-2.4 micrograms/ml. After simplifying the equation, this model was extrapolated to provide an accurate description of the mode of action of other bacteriostatic antibiotics which also inhibit the 50-S ribosomal subunit (tetracycline and doxycycline). The expanded model seems to accurately typify the effect of these antibiotics, whereas bactericidal aminoglycosides follow a completely different growth law.

Chloramphenicol↗
PubMedDate not supplied

Bacterial growth measurement using an automated system: mathematical modelling and analysis of growth kinetics.

The reliability of automated systems was assessed by simultaneously using an MS2 and a methodology of data interpretation/mathematical modelling. Two experimental situations were analysed. Bacterial growth both in synthetic and in complex media could be well described by Monod's model and the logistic model. In the two cases, the fit of the models to the data was satisfactory.

Bacteria↗
PubMedDate not supplied

[Renal differential aging processes and ofloxacin pharmacokinetics in the elderly].

Ageing generates an important inter- and intra-individual variability in drug pharmacokinetics. The increasing frequency of ofloxacin adverse effects in elderly patients results from increased ofloxacin plasma levels about two or threefold over normal concentrations. A retrospective study of ofloxacin population pharmacokinetics in 17 elderly patients (83.6 +/- 6.8 years) shows the existence of three subgroups according to ofloxacin total clearance [group 1: 1.44 l/h, group 2: 4.37 l/h and group 3: 15.08 l/h] reflecting the important inter-individual variability. No correlation between this clearance and creatinine clearance, nor between this clearance and age, could be established, showing the limits of traditional drug monitoring in the elderly. Ofloxacin pharmacokinetic parameters estimated by the non-parametric software NPEM2 in the 17 elderly patients (absorption rate constant, Ka: 2.668 +/- 1.256 h-1; apparent volume of distribution related to weight, Vs: 1.272 +/- 0.778 l/kg; elimination rate constant, Ks: 0.265 +/- 0.247 10(-3) min/ml/h) are clearly different from those estimated in young adults. These results show the limits of classic drug monitoring in the elderly, and also the interest of adaptive control of a drug regimen.

Aged↗
PubMedDate not supplied

[From prevalence to predictive values: considerations on the antimicrobial susceptibility testing dealing with change of susceptibility rates].

The aim of the study was to quantify the influence of the variation of the susceptibility prevalence (frequencies of susceptible, intermediate and resistant isolates) on the predictive value of antimicrobial susceptibility testing reports performed with disk diffusion method, under several scenarios of distinct susceptibility prevalence. Prevalence variation effect was assessed through a modeling approach that enabled to take into account the technical variability and to control prevalence through scenarios. Results show how the prevalence impacts on the disk diffusion performance with level of discrepancies varying with prevalence. The phenomenon may be quantitatively noteworthy for some antimicrobial agents considering the prevalence recorded with time or location, leading to lowered performances. For instance, with amoxicillin+clavulanic acid, predictive values of susceptible and resistant reports varied respectively from 70 to 96 and from 33 to 97 %. For a 18-mm diameter, the probability the isolate is truly susceptible varied from 16 to 73 % according to the prevalence tested. Characteristic of the prevalence effect are described and consequences on zone diameter breakpoint policy raised. They include to (i) reevaluate disk diffusion breakpoint consistency when the prevalence impact is noteworthy and (ii) estimate the consequences of an international harmonized breakpoint policy on prediction quality and appropriate patient management.

Bacterial Infections↗