PubMed Health⌕ Search

Biomedical subjects

G Carret

Publications and source records attributed to G Carret.

At least 19 recordsLinked to original sources

In vitro activity of 10 antimicrobial agents against bacteria isolated from cows with clinical mastitis.

The susceptibility of 495 strains of bacteria, recently isolated in France from cows with clinical mastitis, to 10 antimicrobial agents--penicillin G, cloxacillin, oxacillin, cephalexin, cefazolin, cephapirin, cefquinome, neomycin, ampicillin and colistin--was determined by measuring their minimum inhibitory concentrations (MICS). Overall, the levels of resistance were very low except for staphylococci and penicillin G. The 167 streptococcal strains were susceptible to all of the beta-lactams tested, but six (3-6 per cent) were highly resistant to neomycin. Of the 171 staphylococcal isolates, 36.2 per cent were resistant to penicillin G, one strain of Staphylococcus sciuri was classified as methicillin-resistant, but they were all susceptible to neomycin. None of the 122 strains of Escherichia coli was resistant to colistin, but 12 had high MIC values for one or more of the cephalosporins.

Animals↗

Fitness and competitive growth advantage of new gentamicin-susceptible MRSA clones spreading in French hospitals.

Since 1991, new epidemic methicillin-resistant Staphylococcus aureus (MRSA) strains characterized by the unexpected reappearance of heterogeneous phenotypic expression of resistance to methicillin and by susceptibility to gentamicin and various other antibiotics (GS-MRSA) have been reported in France. GS-MRSA strains have progressively replaced MRSA clones expressing homogeneous resistance to methicillin and resistance to gentamicin (GR-MRSA). In this study, we investigated the physiological characteristics of these new clones. In particular, we evaluated and compared the maximal growth rate and the deduced generation times (related to fitness of strains) of the major French epidemic MRSA clones. The population studied consisted of 79 isolates including (i) GR-MRSA that comprised six different types on the basis of PFGE; (ii) GS-MRSA the majority of which clustered into two PFGE types, A1 (usually resistant to erythromycin) and B (usually susceptible to erythromycin); (iii) methicillin-susceptible S. aureus (MSSA). GS-MRSA-A1 and MSSA strains were shown to have a significant fitness benefit (about 20%) with shorter generation times (theta = 23.7 +/- 0.1 and 22.9 +/- 0.05 min, respectively) than GR-MRSA and GS-MRSA-B strains (theta = 30.3 +/- 0.2 and 32.5 +/- 0.5 min, respectively). These data suggest that a link exists between genetic patterns, resistance profiles and physiological properties. In vitro competitive experiments indicated that GS-MRSA- A1 strains were able to rapidly outgrow GR-MRSA strains. The growth advantage observed should be taken into account in understanding the spread of some new clones of MRSA.

Anti-Bacterial Agents↗

A statistical evaluation of the bactericidal effects of ceftibuten in combination with aminoglycosides and ciprofloxacin.

The bactericidal effects of ceftibuten in combination with netilmicin, isepamicin or ciprofloxacin against two strains of Escherichia coli and three of Klebsiella pneumoniae were studied by the killing curve method. Interpretation of the results was made on a statistical basis by comparing the bactericidal effects observed when the antibiotics were tested alone with those when they were tested in combination. The results were also assessed by survival probabilities according to the ratio of the number of viable bacteria at time t(N(t)) to the initial number of viable bacteria (N(0)). The effects of the combinations were defined in terms of antagonism, indifference, single agonism, addition and synergy by taking account of the confidence intervals of the survival probabilities. All of the combinations exhibited bactericidal activities which were time-dependent. Synergy was demonstrated when ceftibuten was combined with the aminoglycosides, except against the two extended-spectrum beta-lactamase-producing strains of K. pneumoniae, but not when ceftibuten and ciprofloxacin were combined. Antagonism was not demonstrated with any of the combinations.

Aminoglycosides↗

Mathematical model for comparison of time-killing curves.

The relevance of mathematical modeling to investigations of the bactericidal effects of antimicrobial agents has been emphasized in many studies of killing kinetics. We propose here a descriptive model of general use, with four parameters which account for the lag phase, the initial number of bacteria, and the limit of effectiveness and bactericidal rate of antimicrobial agents. The model has been applied to several kinetic datum sets with amoxicillin, cephalothin, nalidixic acid, pefloxacin, and ofloxacin against two Escherichia coli strains. It is a useful tool to compare killing curves by taking into account model parameter confidence limits. This can be illustrated by studying drug effects, strain effects, and concentration effects. For the antibiotics used here, concentration effects had an influence mainly on the length of the lag phase and the minimum number of living cells observed. It is therefore clear that differences in the killing curves with changes in one or more parameters could occur.

Amoxicillin↗

Maintenance requirements of Escherichia coli ATCC 25922 in the presence of sub-inhibitory concentrations of various antibiotics.

Escherichia coli ATCC 25922 was grown in minimal medium M63, with glucose 0.1 gL as limiting energy substrate, in the presence of sub-inhibitory concentrations of netilmicin, habekacin, tobramycin, dibekacin, amikacin, kanamycin, amoxycillin, ampicillin, cephalothin, cefoxitin and nalidixic acid. Maintenance requirements were determined with a simple relationship derived from batch growth curves. The apparent relationship between maintenance requirements and antibiotic concentration is an exponential increase, log m(c) = log mo + k.c, where m is maintenance, c antibiotics concentration, mo maintenance without antibiotics, and k a constant. Values for k were found to be in the range 0.5-2.0 mg-1.L.

Amikacin↗

Biphasic kinetics of bacterial killing by quinolones.

The early phases of the bactericidal dynamics of three quinolones against two Escherichia coli strains were studied. Four concentrations of nalidixic acid, pefloxacin and ofloxacin were tested against each strain. In each case biphasic killing of bacteria was observed after a lag phase, and a biexponential model of microbial death could be fitted to the data. A direct relationship existed between the length of the lag phase and the drug concentration. The other parameters of the model appeared to be either strain-dependent, drug-dependent or both, and were characterised by narrow fluctuations. The degree of killing was always higher for ofloxacin. A paradoxical effect seemed to exist for nalidixic acid and pefloxacin in that survival was greater in the presence of 5 x MIC than in the presence of 3 x MIC. It was clear that ofloxacin did not act in the same way as nalidixic acid and pefloxacin. The study illustrated the relevance of mathematical modelling to investigations of the bactericidal effects of antibiotics.

Colony Count, Microbial↗

[In vitro antibacterial activity of piperacillin-tazobactam combination on hospital isolates and regression curve].

Minimal inhibitory concentrations (MICs) of piperacillin (P) in combination with 4 micrograms/ml of tazobactam (T) were evaluated by agar dilution for 1,245 strains isolated in 4 hospitals. In addition antibiograms by agar diffusion were performed with disks loaded of 75 micrograms of P + 10 micrograms of T. For naturally non beta-lactamase producing Enterobacteriaceae (E), MIC 50 and 90% of P + T were (microgram/ml): E. coli 1-2; P. mirabilis: 0.5-1; activity was practically identical on plasmid mediated penicillinase (Pase) producing strains. Strains of K. pneumoniae only resistant (R) to amino- and carboxypenicillins (C) had MICs less than or equal to 4 (mode MIC 2); MICs of strains R to cephalothin and/or cefotaxime were 2 to 16 (mode MIC 4). For chromosomal cephalosporinase (Case) producing species, MICs of P + T were less than or equal to 8, including for acquired Pase producing strains, but were greater than or equal to 16 for Case hyperproducing strains. Strains of P. aeruginosa susceptible (S) to C were inhibited by 1 to 16 (with MIC 4) and strains R to C by 8 to greater than 128. MICs were generally 2 to 32 for A. baumannii S to C at 0.12 to greater than 128 for strains R to C. Haemophilus, S or R to ampicillin, were inhibited by 0.008 to 2 (MIC 50 and 90: 0.016-0.12). S. aureus S to methicillin (M), Pase producing on not, were inhibited by 0.5 to 2 (mode MIC 1) and strains R to M by 8 to greater than 128. Activity of P + T for coagulase-Staphylococci was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinetobacter↗

[Expert systems and antibiotic sensitivity test].

Artificial intelligence is a part of computer science that deals with programs mimicking intelligence of man. Artificial intelligence is now used to check the quality of the determination of antibiotics susceptibility of bacteria. This application is useful because antibiotic susceptibility is subject to biological and technical variation that have to be detected. Three types of reasoning are used either by the biologist or by expert systems: low level quality checking dealing with individual results, microbiological interpretation of the whole set of results and medical interpretation of the results. The use of artificial intelligence in these fields is sustained by the structured nature of the knowledge. Two type of expert systems are already of routine use, either based on production rules (ATB plus EXPERT, bioMerieux, La Balme-les-Grottes, France and SIR, 12A, Montpellier, France), or on object-oriented representation of the knowledge (EXPRIM from our laboratory). The main problem is, as usually in artificial intelligence applications, to transfer human expertise into an adapted knowledge base. The advantage of experts systems over man are their reproducibility of answer and their availability.

Artificial Intelligence↗

[Mathematical study of the sensitivity curves of Escherichia coli exposed to polymyxins].

The time killing curves of five strains of Escherichia coli (ATCC 25922, ATCC 29194, CIP 54125, CIP 54127, CIP 54117 (K 12)) exposed to five concentrations of polymyxin B are similar: latency phasis, two decreasing phasis and for the low polymyxin B concentrations growth phasis. In our experimental conditions, the Mg(+)+ and Ca(+)+ concentrations of the medium (Mueller-Hinton; medium A: Ca(+)+ = 9 mg/l, Mg(+)+ = 0.5 mg/l; medium B: Ca(+)+ = 35 mg/l, Mg(+)+ = 15.5 mg/l; medium C: Ca(+)+ = 60 mg/l, Mg(+)+ = 20 mg/l) have no time effect upon the killing curves. A decreasing biexponential model can be fitted to the data. Such a model is compatible with interaction between antibiotic and bacterium and can be formalized accorrding to the equation: T + ATB K1 in equilibrium of K2 T* - ATB K3----ATB + dead with ATB: Polymyxine B in excess, T: target bacterium and T*: modification target bacterium.

Escherichia coli↗

[Bacteriostatic and bactericidal antibiotics: differences in subinhibitory concentration effects on the growth of Escherichia coli].

The growth of Escherichia coli in synthetic medium was mathematically analysed at subinhibitory levels of bactericidal and bacteriostatic antibiotics. Over a threshold of concentration, bactericidal antibiotics induce an unexpected change of growth pattern. Bacteriostatic antibiotics induce a progressive effect linked to a continuously altered growth pattern that still remains close to the controls. This fundamental differential of antibiotic effects is reflecting well-known bacteriostatic or bactericidal phenomena. In vitro this analysis of the growth enables to measure the level of the antibiotic sensitivity. In vivo, these results must be taken into account when subinhibitory concentrations of antimicrobial agent are reached at the infection site.

Anti-Bacterial Agents↗

[Interpretative reading and quality control of an antibiotic sensitivity test using an expert system. Application to the API ATB system and Enterobacteriaceae].

An expert system (cadi-yac), written in Turbo-Prolog and working on IBM PC and Bacanal + (a management software of microbiology laboratory) was used to recognize and correct the phenotype of antibiotic sensibility. The results were there of API ATB system. The knowledge was adapted from two references works. A routine use of the expert system give a correct recognition of enzymatic profile in more than 80% cases for the beta-lactams and more than 98% cases for the aminosides. The mistakes detected by cadi-yac, were often interpreted as deficiency of API system by humans experts. The expert system mistakes (1.5%) were due composites phenotypes.

Anti-Bacterial Agents↗

Early stages of in vitro killing curve of LY146032 and vancomycin for Staphylococcus aureus.

The early stages of the time-killing curves of vancomycin and LY146032 have been studied, by use of short sampling intervals, for three strains of Staphylococcus aureus. Both vancomycin and LY146032 killed S. aureus, but the time-killing curves differed: the effect of vancomycin was slow, limited, and not related to the concentration of the drug, whereas that of LY146032 was rapid, extensive, and related to concentration. When strains ATCC 25923 and CIP 6525 were exposed to LY146032, the population decreased exponentially with time. The killing rate was constant and linked to the concentration by a Michaelis-Menten relationship. The maximum killing rate and the affinity constant of LY146032, estimated from the data transformed by the Lineweaver-Burk method, differed for the two strains. The concentration of the antibiotic at which killing theoretically begins (estimated by linear regression using the logarithm of the concentration) is of the same magnitude as the MIC of LY146032, which indicates the pure bactericidal mode of action of the drug. S. aureus ATCC 12600 was more resistant to the bactericidal effect of the two drugs, and its killing curve did not conform to the model described here.

Anti-Bacterial Agents↗

[Demonstration of an inoculum effect on the estimation of the minimal inhibitory concentration of LY 146032].

This work has been performed to study the inoculum effect on the in vitro activity of LY 146032, a new lipopeptide antibiotic. A statistical analysis (X2 and t test) of the data concerning the MIC of different bacterial groups has been carried out to appreciate the phenomenon. The activity of vancomycin has been compared. A major inoculum effect has been detected for LY 146032. It must be taken into account to evaluate the activity of this new antibiotic.

Anti-Bacterial Agents↗

[A mathematical study of the mortality curve of Escherichia coli exposed to aminoglycosides].

The time killing curves of three strains of E. coli (CIP54117, ATCC25922 and ATCC29194) exposed to kanamycin, amikacin, netilmicin and dibekacin are decreasing exponentials. The absolute value of the killing rate m is related to the antibiotic concentration through a Michaelis-Henry equation. A maximum killing rate m max and an affinity constant Kc between bacteria and antibiotic can thus be estimated. m max is mainly strain dependent. On the contrary, Kc is related to the antibiotic. Kc is much higher (i.e. the affinity is much lower) for kanamycin and amikacin than for netilmicin or dibekacin. The dose-effect curve is a saturation curve. Increasing doses of antibiotic do not increase the mortality proportionally.

Amikacin↗

[Use of an expert system as a tool to carry out urinary cyto-bacteriologic tests].

An expert system for urine examinations was developed. Its validation was performed in a routine work, by comparison of expert decisions with software conclusions. Results of finished examinations or in progress were taken into account. The agreement was satisfactory. In addition to reliability, advantages constituted by availability, flexibility and adaptability were notified. Repeatability and reproducibility were also emphasized.

Algorithms↗