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Biomedical subjects

Henri Monteil

Publications and source records attributed to Henri Monteil.

25 records · Page 2Linked to original sources

Isolation of sulfate-reducing bacteria from human thoracoabdominal pus.

To evaluate the prevalence of sulfate-reducing bacteria in septic processes, we searched for these bacteria by culture in 100 consecutive abdominal and pleural pus specimens. Twelve isolates were obtained from abdominal samples and were identified by a multiplex PCR as Desulfovibrio piger (formerly Desulfomonas pigra) (seven strains), Desulfovibrio fairfieldensis (four strains), and Desulfovibrio desulfuricans (one strain).

Abdomen↗

Protein engineering modulates the transport properties and ion selectivity of the pores formed by staphylococcal gamma-haemolysins in lipid membranes.

Staphylococcal gamma-haemolysins are bicomponent toxins in a family including other leucocidins and alpha-toxin. Two active toxins are formed combining HlgA or HlgC with HlgB. Both open pores in lipid membranes with conductance, current voltage characteristics and stability similar to alpha-toxin, but different selectivity (cation instead of anion). Structural analogies between gamma-haemolysins and alpha-toxin indicate the presence, at the pore entry, of a conserved region containing four positive charges in alpha-toxin, but either positive or negative in gamma-haemolysins. Four mutants were produced (HlgA D44K, HlgB D47K, HlgB D49K and HlgB D47K/D49K) converting those negative charges to positive in HlgA and HlgB. When all charges were positive, the pores had the same selectivity and conductance as alpha-toxin, suggesting that the cluster may form an entrance electrostatic filter. As mutated HlgC-HlgB pores were less affected, additional charges in the lumen of the pore were changed (HlgB E107Q, HlgB D121N, HlgB T136D and HlgA K108T). Removing a negative charge from the lumen made the selectivity of both HlgA-HlgB D121N and HlgC-HlgB D121N more anionic. Residue D121 of HlgB is compensated by a positive residue (HlgA K108) in the HlgA-HlgB pore, but isolated in the more cation-selective HlgC-HlgB pore. Interestingly, the pore formed by HlgA K108T-HlgB, in which the positive charge of HlgA was removed, was as cation selective as HlgC-HlgB. Meanwhile, the pore formed by HlgA K108T-HlgB D121N, in which the two charge changes compensated, retrieved the properties of wild-type HlgA-HlgB. We conclude that the conductance and selectivity of the gamma-haemolysin pores depend substantially on the presence and location of charged residues in the channel.

Amino Acid Sequence↗

Bartonella bovis Bermond et al. sp. nov. and Bartonella capreoli sp. nov., isolated from European ruminants.

Two novel species of Bartonella isolated from European ruminants are described. Bartonella capreoli sp. nov. was isolated from the blood of roe-deer (Capreolus capreolus) captured in Chizé, France. The type strain is IBS 193T (= CIP 106691T = CCUG 43827T). It is distinct from another European ruminant isolate that originated from a cow from a French herd of 430 dairy cattle. The latter isolate belongs to a novel species named Bartonella bovis Bermond et al. sp. nov. The type strain is strain 91-4T (= CIP 106692T = CCUG 43828T). The two bacteria appeared as small, fastidious, aerobic, oxidase-negative, gram-negative rods. Their biochemical properties were similar to those of members of the genus Bartonella. The sequences of the 16S rRNA and citrate synthase genes obtained from the two type strains were highly related to sequences of the different Bartonella species. Hybridization values when testing type strains of recognized Bartonella species, obtained with the nuclease/trichloroacetic acid method, support the creation of two novel species.

Animals↗

Ex vivo pharmacodynamics of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli in a yucatan miniature pig model that mimics human pharmacokinetics.

The objective of the present study was to investigate the potential bactericidal activity of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli strains and to elucidate the extent to which enzyme production affects the activity. Six adult Yucatan miniature pigs received a single intravenous dose of 1.1 g of amoxicillin-clavulanate as an intravenous infusion over 30 min. The pharmacokinetic parameters were determined for the serum samples and compared to the published data for humans (2.2-g intravenous dose). The parameters were comparable for the two species, and therefore, the miniature pig constitutes a good model for pharmacodynamic study of amoxicillin-clavulanate. Therefore, the model was used in an ex vivo pharmacodynamic study of amoxicillin-clavulanate against four strains of Escherichia coli producing beta-lactamases at different levels. The E. coli strains were cultured with serial dilutions (1:2 to 1:256) of the serum samples from the pharmacokinetic study, and the number of surviving bacteria was determined after 1, 3, and 6 h of exposure. Amoxicillin-clavulanate at concentrations less than the MIC and the minimal bactericidal concentration had marked bactericidal potency against the strain that produced low levels of penicillinase. For high-level or intermediate-level beta-lactamase-producing strains, the existence of a clavulanate concentration threshold of 1.5 to 2 micro g/ml, below which there was no bactericidal activity, was demonstrated. The index of surviving bacteria showed the existence of mixed concentration- and time-dependent actions of amoxicillin (in the presence of clavulanate) which varied as a function of the magnitude of beta-lactamase production by the test strains. This study shows the effectiveness of amoxicillin-clavulanate against low- and intermediate-level penicillinase-producing strains of E. coli. These findings are to be confirmed in a miniature pig experimental infection model.

Amoxicillin-Potassium Clavulanate Combination↗

Pharmacokinetics in vivo and pharmacodynamics ex vivo/in vitro of meropenem and cefpirome in the Yucatan micropig model: continuous infusion versus intermittent injection.

OBJECTIVE: To investigate the pharmacodynamic disposition of two recently developed beta-lactam antibiotics, meropenem and cefpirome, in the Yucatan micropig model, and to compare the bactericidal activity of these drugs against bacteria in this in vitro/ex vivo micropig model after administration by both intermittent injection and continuous infusion. METHODS: Cefpirome (1 g) was given to the micropig over a 12-h period by direct intravenous injection and 6-h continuous infusion (500 mg). Meropenem (250 mg) was administered either by 30-min intravenous and 8-h continuous infusion. The two drugs were assayed by HPLC. The pharmacodynamics of these drugs were evaluated by means of (1) serum killing curve against Klebsiella pneumoniae producing extended-spectrum beta-lactamase, stably derepressed Enterobacter cloacae and methicillin-susceptible penicillinase-producing Staphylococcus aureus, and (2) calculations of index of surviving bacteria (ISB). RESULTS: The bactericidal activity of meropenem against K. pneumoniae and E. cloacae in this in vitro/ex vivo model was excellent, with a 4 log decrease at peak concentrations. Meropenem produced a mixed concentration- and time-dependent, killing effect against E. cloacae and K. pneumoniae. The ISB value ranged from 25% to 30% for E. cloacae. With concentrations above MIC for S. aureus (1 mg/L), cefpirome has a time-dependent bactericidal activity, as shown by the ISB ranging from 20% to 80% after 4 h and between 20% and 40% after an 8-h drug exposure. For both antibiotics, the higher concentrations obtained just after intermittent injection had a rapid and strong killing effect against the strains tested, but the trough levels had no bactericidal activity. The continuous infusions produce consistent concentrations of antibiotic that can be maintained above the MIC, and the bactericidal activity of which ranges from 2 to 4 log10 decrease of inoculum. CONCLUSIONS: In the present study the micropig has been shown to be an adequate model for the pharmacodynamic investigation of cefpirome and meropenem. In general, continuous infusion appears to optimize the pharmacodynamic profile of the two tested beta-lactam antibiotics. However, against Gram-negative bacilli, the administration of a loading dose prior to continuous infusion of beta-lactams would eliminate the only potential pharmacokinetic disadvantage of continuous infusion and ensure the rapid onset of antimicrobial activity.

Journal Article↗

The effect of rifampin on the pharmacokinetics of vinorelbine in the micropig.

BACKGROUND: Vinorelbine has been shown to be metabolised by CYP3A4 in vitro. To evaluate the impact of CYP3A in the disposition of vinorelbine in vivo, we compared the kinetics of the alkaloid given intravenously alone and combined with rifampin, a potent CYP3A inducer, in the micropig. ANIMALS AND METHODS: Four healthy Yucatan micropigs, about 20 kg, received a first infusion of vinorelbine (0.5 mg/kg). During the next week they were injected rifampin (600 mg daily) and a second vinorelbine infusion (0.5 mg/kg) on the 7th day of rifampin dosing. Serum concentrations of vinorelbine and rifampin were measured by high performance liquid chromatography. RESULTS: The mean peak concentrations of vinorelbine were 274.2 ng/ml (Standard Deviation or SD: 90) and 458 ng/ml (SD: 448), the mean areas under the serum concentration-time curve were 8,344 ng.min.ml-1 (SD: 2,604) and 14,093 ng/ml.min-1 (SD: 10,000) and the total clearances were 1.146 l/min (SD: 0.333) and 1.003 l/min (SD: 0.714) when the Catharanthus alkaloid was given alone or was combined with rifampin, respectively. CONCLUSION: We did not observe an increase in vinorelbine elimination by rifampin related to a CYP3A induction in an animal model physiologically close to humans. Although the number of animals was small, these results suggest that CYP3A metabolism constitutes a minor pathway of elimination of intravenous vinorelbine in the micropig.

Animals↗