M. Odou - Academia.edu (original) (raw)
Papers by M. Odou
Annales d'Endocrinologie, 2021
Revue des Maladies Respiratoires, 2020
INTRODUCTION Alpha1-antitrypsin deficiency is a predisposing factor for pulmonary disease and und... more INTRODUCTION Alpha1-antitrypsin deficiency is a predisposing factor for pulmonary disease and under-diagnosis is a significant problem. The results of a targeted screening in patients with respiratory symptoms possibly indicative of severe deficiency are reported here. METHODS Data were collected from March 2016 to October 2017 on patients who had a capillary blood sample collected during a consultation with a pulmonologist and sent to the laboratory for processing to determine alpha1-antitrypsin concentration, phenotype and possibly genotype. RESULTS In 20 months, 3728 test kits were requested by 566 pulmonologists and 718 (19 %) specimens sent: among these, 708 were analyzable and 613 were accompanied by clinical information. Of the 708 samples, 70 % had no phenotype associated with quantitative alpha1- antitrypsin deficiency, 7 % had a phenotype associated with a severe deficiency and 23 % had a phenotype associated with an intermediate deficiency. One hundred and eight patients carried at least one PI*Z allele which is considered to be a risk factor for liver disease. CONCLUSIONS The results of this targeted screening program for alpha1- antitrypsin deficiency using a dried capillary blood sample reflect improvement in early diagnosis of this deficiency in lung disease with good adherence of the pulmonologists to this awareness campaign.
Revue des Maladies Respiratoires, 2020
Annales d'Endocrinologie, 2020
Annales d'Endocrinologie - In Press. Accepted Manuscript Available online since vendredi 10 a... more Annales d'Endocrinologie - In Press. Accepted Manuscript Available online since vendredi 10 avril 2020
Orphanet Journal of Rare Diseases, 2017
The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regula... more The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The diseases caused by an abnormality of the CaSR are genetically determined or are more rarely acquired. The genetic diseases consist of hyper-or hypocalcemia disorders. Hypercalcaemia disorders are related to inactivating mutations of the CASR gene either heterozygous (autosomal dominant familial benign hypercalcaemia, still named hypocalciuric hypercalcaemia syndrome type 1) or homozygous (severe neonatal hyperparathyroidism). The A986S, R990G and Q1011E variants of the CASR gene are associated with higher serum calcium levels than in the general population, hypercalciuria being also associated with the R990G variant. The differential diagnosis consists in the hypocalciuric hypercalcaemia syndrome, types 2 (involving GNA11 gene) and 3 (involving AP2S1 gene); hyperparathyroidism; abnormalities of vitamin D metabolism, involving CYP24A1 and SLC34A1 genes; and reduced GFR. Hypocalcemia disorders, which are more rare, are related to heterozygous activating mutations of the CASR gene (type 1), consisting of autosomal dominant hypocalcemia disorders, sometimes with a presentation of pseudo-Bartter's syndrome. The differential diagnosis consists of the hypercalciuric hypocalcaemia syndrome type 2, involving GNA11 gene and other hypoparathyroidism aetiologies. The acquired diseases are related to the presence of anti-CaSR antibodies, which can cause hyper-or especially hypocalcemia disorders (for instance in APECED syndromes), determined by their functionality. Finally, the role of CaSR in digestive, respiratory, cardiovascular and neoplastic diseases is gradually coming to light, providing new therapeutic possibilities. Two types of CaSR modulators are known: CaSR agonists (or activators, still named calcimimetics) and calcilytic antagonists (or inhibitors of the CasR). CaSR agonists, such as cinacalcet, are indicated in secondary and primary hyperparathyroidism. Calcilytics have no efficacy in osteoporosis, but could be useful in the treatment of hypercalciuric hypocalcaemia syndromes.
Revue des Maladies Respiratoires, 2016
RMR-1066; No. of Pages 6 2 J. Perrin et al. à 3 paquets-années. Le scanner thoracique montrait un... more RMR-1066; No. of Pages 6 2 J. Perrin et al. à 3 paquets-années. Le scanner thoracique montrait un emphysème panlobulaire diffus. La concentration sérique d'alpha-1 antitrypsine était effondrée. Le phénotypage par focalisation isoélectrique en gel d'agarose ne montrait aucune bande. L'étude du gène SERPINA1, par PCRséquence des exons II, III, IV et V et les séquences introniques flanquantes, révélait un allèle NullQ0o urém à l'état homozygote. Le cas index présentait une aggravation rapide du trouble ventilatoire obstructif. Conclusion.-Dans le cas d'un déficit en alpha-1 antitrypsine sérique, l'analyse du phénotype de la protéine par isoélectrofocalisation doit être réalisée en première intention. La mise en évidence d'un profil atypique doit faire évoquer la présence d'allèles déficitaires autres que PI S et PI Z qui ne peuvent être caractérisés que par séquençage complet du gène SERPINA1. Les patients porteurs d'une mutation Null ont un risque élevé de bronchopneumopathie chronique obstructive sévère.
European journal of endocrinology / European Federation of Endocrine Societies, Jan 21, 2015
Multiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 g... more Multiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the GTE-cohort associated with a mutations in the JunD interacting domain, suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intra-familial correlations and heritability of the six main tumor types in MEN1. The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs), pituitary, adrenal, bronchial and thymic tumors (ThNETs) and the presence of metastasis. Intra-familial correlations and heritability estimates were calculated from family tree data using specific validated statistical analys...
Annales de biologie clinique, 2013
Laboratory waste management must ensure the safety of patients and staff, limiting the environmen... more Laboratory waste management must ensure the safety of patients and staff, limiting the environmental impacts and control waste disposal budget. Sorting of waste must be carried out at the source. The packaging must be adapted, allowing easy identification of specific disposal routes. With regard to wastes for human or animal health care and/or related research (DASRI), packages must comply with the regulations, standards and ADR if necessary. Storage provisions differ according to the amount of DASRI produced. Waste collection is carried out directly on the place of activity by a certified service provider. Non pre-treated DASRI is incinerated in specific approved plants for a T ° > 1,200 °C. Special provisions also exist for chemical waste and radioactive waste, the latter being regulated by ANDRA.
Annales de biologie clinique, 2013
Risk management in Medical Biology Laboratory (MBL) which includes hygiene and waste management, ... more Risk management in Medical Biology Laboratory (MBL) which includes hygiene and waste management, is an integrated process to the whole MBL organisation. It is composed of three stages: risks factors identification, grading and prioritization, and their evaluation in the system. From the legislation and NF EN ISO 15189 standard's requirements viewpoint, prevention and protection actions to implement are described, at premises level, but also at work station environment's one (human resources and equipments) towards biological, chemical, linked to gas, to ionizing or non ionizing radiations and fire riks, in order not to compromise patients safety, employees safety, and quality results. Then, although NF EN 15189 standard only enacts requirements in terms of prevention, curative actions after established blood or chemical exposure accident are defined.
Revue des Maladies Respiratoires, 2014
Revue des Maladies Respiratoires, 2014
RMR-819; No. of Pages 11 2 M. Balduyck et al. antiélastasique sérique. Si un déficit pondéral ou ... more RMR-819; No. of Pages 11 2 M. Balduyck et al. antiélastasique sérique. Si un déficit pondéral ou fonctionnel est détecté, deux démarches complémentaires peuvent être envisagées : la détermination du phénotype d'␣ 1-AT par isoélectrofocalisation qui permet d'identifier les variants normaux PI M mais aussi un certain nombre de variants déficitaires, dont les plus fréquents, PI S et PI Z, ou le génotypage par PCR allèle-spécifique qui permet de caractériser les allèles déficitaires PI S et PI Z. Le recours au séquençage complet des exons codants du gène SERPINA1 se justifie pour l'identification précise des allèles déficitaires rares et des allèles qualifiés de Null.
Anaerobe, 2010
The purpose of this article is to set out some important considerations on the main emerging anti... more The purpose of this article is to set out some important considerations on the main emerging antibiotic resistance patterns among anaerobic bacteria. The first point concerns the Bacteroides fragilis group and its resistance to the combination of b-lactam þ b-lactamase inhibitor. When there is overproduction of cephalosporinase, it results in increased resistance to the b-lactams while maintaining susceptibility to b-lactams/b-lactamase inhibitor combinations. However, if another resistance mechanism is added, such as a loss of porin, resistances to b-lactam þ b-lactamase inhibitor combinations may occur. The second point is resistance to metronidazole occurring due to nim genes. PCR detection of nim genes alone is not sufficient for predicting resistance to metronidazole; actual MIC determinations are required. Therefore, it can be assumed that other resistance mechanisms can also be involved. Although metronidazole resistance remains rare for the B. fragilis group, it has nevertheless been detected worldwide and also been observed spreading to other species. In some cases where there is only a decreased susceptibility, clinical failures may occur. The last point concerns resistance of Clostridium species to glycopeptides and lipopeptides. Low levels of resistance have been detected with these antibiotics. Van genes have been detected not only in clostridia but also in other species. In conclusion, antibiotic resistance involves different mechanisms and affects many anaerobic species and is spreading worldwide. This demonstrates the need to continue with antibiotic resistance testing and surveys in anaerobic bacteria.
Pulmonary Pharmacology & Therapeutics, 2010
Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, adminis... more Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact. Twenty-four patients hospitalised for community-acquired pulmonary infections received amikacin by IV route over 1 h with a targeted peak concentration of 35 mg/L. They were randomly distributed into two groups, one receiving infusion through a pump system, the other by gravity. Amikacin serum levels were determined at the end of infusion and 24 h later. C max values were significantly lower with gravity than pump (40.2 AE 12.3 vs. 50.6 AE 17.6 mg/L, respectively; p ¼ 0.04). Elimination half-life time, volume of distribution and clearance did not differ significantly from one group to the other. The percentage of patients who failed to achieve the targeted peak concentration was significantly higher with gravity than pump (41.7% vs. 16.7%, respectively; p < 0.001). Improving infusion flow-rate provides better control over amikacin C max. This study underlines the fact that infusion device characteristics should be added to the physiopathological information of a patient if we are to make a better estimation of pharmacokinetic parameters.
Journal of Antimicrobial Chemotherapy, 2007
Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial f... more Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin. Methods: The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6). Results: Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by 2 mg/L. Conclusions: At 2 mg/L, retapamulin inhibited 90% of all 232 anaerobes tested, whereas overall resistance rates for the comparators were as follows: co-amoxiclav, 2%; metronidazole, 12%; clindamycin, 15% and ceftriaxone, 20%. The broad anaerobic spectrum demonstrated by retapamulin in vitro is attractive. Pending further clinical investigation, retapamulin may offer an alternative treatment for anaerobic skin infections in this era of increasing resistance.
FEMS Microbiology Letters, 1998
Journal of Medical Genetics, 2003
Annales d'endocrinologie, 2006
Calcium is a major ion in human metabolism and its level is highly controlled. This regulation is... more Calcium is a major ion in human metabolism and its level is highly controlled. This regulation is performed via the Calcium Sensing Receptor, a discovery which ten years ago led to the explanation of a number of clinical disorders. The syndromes caused by CaSR abnormalities are characterized by hypercalcemia or hypocalcemia, associated with inappropriate calciuria. An underlying genetic or auto-immune cause may be demonstrated. High blood calcium levels linked to mutations of the CaSR gene lead to familial hypocalciuric hypercalcemia and the neonatal and non neonatal forms with severe hypercalcemic. Hypocalcemia determined by mutations in the CaSR gene include autosomal dominant hypocalcemia and its sporadic form. Another clinical presentation similar to Bartter syndrome has been reported. Auto-antibodies directed against CaSRs, seen in auto-immune diseases, can lead to similar clinical presentations. Finally, CaSR polymorphisms modulate the range of blood calcium levels. With diagn...
Anaerobe, 1999
Cell-free whey from a selected strain, Bifidobacterium breve C50, induced an increase in bifidoba... more Cell-free whey from a selected strain, Bifidobacterium breve C50, induced an increase in bifidobacteria associated with a Bacteroides fragilis reduction in the gut of conventional mice and humans. The purpose of our study was to investigate the mechanism of B. fragilis repression. C50 cell-free whey was given for 15 days to conventional or ex-germ-free mice mono-associated to the strain B. fragilis CFPL 358. Conventional and ex-germ-free control mice received whey which was incapable of promoting intestinal bifidobacteria and of reducing B. fragilis. Bacterial counting was carried out in the ileum, caecum and colon of both mouse models. The C50 cell-free whey induced a significant increase in endogenous bifidobacteria in the ileum of conventional mice, whereas B. fragilis was below detectable levels throughout the intestine. In ex-germ-free mice mono-associated with B. fragilis, the strain was seen to be at a high level through the whole intestine and no significant difference in counts was observed according to the whey administered to animals. The data indicated that a prerequisite for C50 cell-free whey repressive activity against B. fragilis is colonization of the mouse gut with complex bacterial microflora. With the exception of the distal ileum, the bifidobacterial overgrowth did not, however, support B. fragilis reduction. It is likely that in the caecum and colon some other bacteria participated in the process.
Pulmonary Pharmacology & Therapeutics, 2010
Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, adminis... more Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact.
Annales d'Endocrinologie, 2021
Revue des Maladies Respiratoires, 2020
INTRODUCTION Alpha1-antitrypsin deficiency is a predisposing factor for pulmonary disease and und... more INTRODUCTION Alpha1-antitrypsin deficiency is a predisposing factor for pulmonary disease and under-diagnosis is a significant problem. The results of a targeted screening in patients with respiratory symptoms possibly indicative of severe deficiency are reported here. METHODS Data were collected from March 2016 to October 2017 on patients who had a capillary blood sample collected during a consultation with a pulmonologist and sent to the laboratory for processing to determine alpha1-antitrypsin concentration, phenotype and possibly genotype. RESULTS In 20 months, 3728 test kits were requested by 566 pulmonologists and 718 (19 %) specimens sent: among these, 708 were analyzable and 613 were accompanied by clinical information. Of the 708 samples, 70 % had no phenotype associated with quantitative alpha1- antitrypsin deficiency, 7 % had a phenotype associated with a severe deficiency and 23 % had a phenotype associated with an intermediate deficiency. One hundred and eight patients carried at least one PI*Z allele which is considered to be a risk factor for liver disease. CONCLUSIONS The results of this targeted screening program for alpha1- antitrypsin deficiency using a dried capillary blood sample reflect improvement in early diagnosis of this deficiency in lung disease with good adherence of the pulmonologists to this awareness campaign.
Revue des Maladies Respiratoires, 2020
Annales d'Endocrinologie, 2020
Annales d'Endocrinologie - In Press. Accepted Manuscript Available online since vendredi 10 a... more Annales d'Endocrinologie - In Press. Accepted Manuscript Available online since vendredi 10 avril 2020
Orphanet Journal of Rare Diseases, 2017
The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regula... more The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The diseases caused by an abnormality of the CaSR are genetically determined or are more rarely acquired. The genetic diseases consist of hyper-or hypocalcemia disorders. Hypercalcaemia disorders are related to inactivating mutations of the CASR gene either heterozygous (autosomal dominant familial benign hypercalcaemia, still named hypocalciuric hypercalcaemia syndrome type 1) or homozygous (severe neonatal hyperparathyroidism). The A986S, R990G and Q1011E variants of the CASR gene are associated with higher serum calcium levels than in the general population, hypercalciuria being also associated with the R990G variant. The differential diagnosis consists in the hypocalciuric hypercalcaemia syndrome, types 2 (involving GNA11 gene) and 3 (involving AP2S1 gene); hyperparathyroidism; abnormalities of vitamin D metabolism, involving CYP24A1 and SLC34A1 genes; and reduced GFR. Hypocalcemia disorders, which are more rare, are related to heterozygous activating mutations of the CASR gene (type 1), consisting of autosomal dominant hypocalcemia disorders, sometimes with a presentation of pseudo-Bartter's syndrome. The differential diagnosis consists of the hypercalciuric hypocalcaemia syndrome type 2, involving GNA11 gene and other hypoparathyroidism aetiologies. The acquired diseases are related to the presence of anti-CaSR antibodies, which can cause hyper-or especially hypocalcemia disorders (for instance in APECED syndromes), determined by their functionality. Finally, the role of CaSR in digestive, respiratory, cardiovascular and neoplastic diseases is gradually coming to light, providing new therapeutic possibilities. Two types of CaSR modulators are known: CaSR agonists (or activators, still named calcimimetics) and calcilytic antagonists (or inhibitors of the CasR). CaSR agonists, such as cinacalcet, are indicated in secondary and primary hyperparathyroidism. Calcilytics have no efficacy in osteoporosis, but could be useful in the treatment of hypercalciuric hypocalcaemia syndromes.
Revue des Maladies Respiratoires, 2016
RMR-1066; No. of Pages 6 2 J. Perrin et al. à 3 paquets-années. Le scanner thoracique montrait un... more RMR-1066; No. of Pages 6 2 J. Perrin et al. à 3 paquets-années. Le scanner thoracique montrait un emphysème panlobulaire diffus. La concentration sérique d'alpha-1 antitrypsine était effondrée. Le phénotypage par focalisation isoélectrique en gel d'agarose ne montrait aucune bande. L'étude du gène SERPINA1, par PCRséquence des exons II, III, IV et V et les séquences introniques flanquantes, révélait un allèle NullQ0o urém à l'état homozygote. Le cas index présentait une aggravation rapide du trouble ventilatoire obstructif. Conclusion.-Dans le cas d'un déficit en alpha-1 antitrypsine sérique, l'analyse du phénotype de la protéine par isoélectrofocalisation doit être réalisée en première intention. La mise en évidence d'un profil atypique doit faire évoquer la présence d'allèles déficitaires autres que PI S et PI Z qui ne peuvent être caractérisés que par séquençage complet du gène SERPINA1. Les patients porteurs d'une mutation Null ont un risque élevé de bronchopneumopathie chronique obstructive sévère.
European journal of endocrinology / European Federation of Endocrine Societies, Jan 21, 2015
Multiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 g... more Multiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the GTE-cohort associated with a mutations in the JunD interacting domain, suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intra-familial correlations and heritability of the six main tumor types in MEN1. The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs), pituitary, adrenal, bronchial and thymic tumors (ThNETs) and the presence of metastasis. Intra-familial correlations and heritability estimates were calculated from family tree data using specific validated statistical analys...
Annales de biologie clinique, 2013
Laboratory waste management must ensure the safety of patients and staff, limiting the environmen... more Laboratory waste management must ensure the safety of patients and staff, limiting the environmental impacts and control waste disposal budget. Sorting of waste must be carried out at the source. The packaging must be adapted, allowing easy identification of specific disposal routes. With regard to wastes for human or animal health care and/or related research (DASRI), packages must comply with the regulations, standards and ADR if necessary. Storage provisions differ according to the amount of DASRI produced. Waste collection is carried out directly on the place of activity by a certified service provider. Non pre-treated DASRI is incinerated in specific approved plants for a T ° > 1,200 °C. Special provisions also exist for chemical waste and radioactive waste, the latter being regulated by ANDRA.
Annales de biologie clinique, 2013
Risk management in Medical Biology Laboratory (MBL) which includes hygiene and waste management, ... more Risk management in Medical Biology Laboratory (MBL) which includes hygiene and waste management, is an integrated process to the whole MBL organisation. It is composed of three stages: risks factors identification, grading and prioritization, and their evaluation in the system. From the legislation and NF EN ISO 15189 standard's requirements viewpoint, prevention and protection actions to implement are described, at premises level, but also at work station environment's one (human resources and equipments) towards biological, chemical, linked to gas, to ionizing or non ionizing radiations and fire riks, in order not to compromise patients safety, employees safety, and quality results. Then, although NF EN 15189 standard only enacts requirements in terms of prevention, curative actions after established blood or chemical exposure accident are defined.
Revue des Maladies Respiratoires, 2014
Revue des Maladies Respiratoires, 2014
RMR-819; No. of Pages 11 2 M. Balduyck et al. antiélastasique sérique. Si un déficit pondéral ou ... more RMR-819; No. of Pages 11 2 M. Balduyck et al. antiélastasique sérique. Si un déficit pondéral ou fonctionnel est détecté, deux démarches complémentaires peuvent être envisagées : la détermination du phénotype d'␣ 1-AT par isoélectrofocalisation qui permet d'identifier les variants normaux PI M mais aussi un certain nombre de variants déficitaires, dont les plus fréquents, PI S et PI Z, ou le génotypage par PCR allèle-spécifique qui permet de caractériser les allèles déficitaires PI S et PI Z. Le recours au séquençage complet des exons codants du gène SERPINA1 se justifie pour l'identification précise des allèles déficitaires rares et des allèles qualifiés de Null.
Anaerobe, 2010
The purpose of this article is to set out some important considerations on the main emerging anti... more The purpose of this article is to set out some important considerations on the main emerging antibiotic resistance patterns among anaerobic bacteria. The first point concerns the Bacteroides fragilis group and its resistance to the combination of b-lactam þ b-lactamase inhibitor. When there is overproduction of cephalosporinase, it results in increased resistance to the b-lactams while maintaining susceptibility to b-lactams/b-lactamase inhibitor combinations. However, if another resistance mechanism is added, such as a loss of porin, resistances to b-lactam þ b-lactamase inhibitor combinations may occur. The second point is resistance to metronidazole occurring due to nim genes. PCR detection of nim genes alone is not sufficient for predicting resistance to metronidazole; actual MIC determinations are required. Therefore, it can be assumed that other resistance mechanisms can also be involved. Although metronidazole resistance remains rare for the B. fragilis group, it has nevertheless been detected worldwide and also been observed spreading to other species. In some cases where there is only a decreased susceptibility, clinical failures may occur. The last point concerns resistance of Clostridium species to glycopeptides and lipopeptides. Low levels of resistance have been detected with these antibiotics. Van genes have been detected not only in clostridia but also in other species. In conclusion, antibiotic resistance involves different mechanisms and affects many anaerobic species and is spreading worldwide. This demonstrates the need to continue with antibiotic resistance testing and surveys in anaerobic bacteria.
Pulmonary Pharmacology & Therapeutics, 2010
Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, adminis... more Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact. Twenty-four patients hospitalised for community-acquired pulmonary infections received amikacin by IV route over 1 h with a targeted peak concentration of 35 mg/L. They were randomly distributed into two groups, one receiving infusion through a pump system, the other by gravity. Amikacin serum levels were determined at the end of infusion and 24 h later. C max values were significantly lower with gravity than pump (40.2 AE 12.3 vs. 50.6 AE 17.6 mg/L, respectively; p ¼ 0.04). Elimination half-life time, volume of distribution and clearance did not differ significantly from one group to the other. The percentage of patients who failed to achieve the targeted peak concentration was significantly higher with gravity than pump (41.7% vs. 16.7%, respectively; p < 0.001). Improving infusion flow-rate provides better control over amikacin C max. This study underlines the fact that infusion device characteristics should be added to the physiopathological information of a patient if we are to make a better estimation of pharmacokinetic parameters.
Journal of Antimicrobial Chemotherapy, 2007
Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial f... more Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin. Methods: The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6). Results: Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by 2 mg/L. Conclusions: At 2 mg/L, retapamulin inhibited 90% of all 232 anaerobes tested, whereas overall resistance rates for the comparators were as follows: co-amoxiclav, 2%; metronidazole, 12%; clindamycin, 15% and ceftriaxone, 20%. The broad anaerobic spectrum demonstrated by retapamulin in vitro is attractive. Pending further clinical investigation, retapamulin may offer an alternative treatment for anaerobic skin infections in this era of increasing resistance.
FEMS Microbiology Letters, 1998
Journal of Medical Genetics, 2003
Annales d'endocrinologie, 2006
Calcium is a major ion in human metabolism and its level is highly controlled. This regulation is... more Calcium is a major ion in human metabolism and its level is highly controlled. This regulation is performed via the Calcium Sensing Receptor, a discovery which ten years ago led to the explanation of a number of clinical disorders. The syndromes caused by CaSR abnormalities are characterized by hypercalcemia or hypocalcemia, associated with inappropriate calciuria. An underlying genetic or auto-immune cause may be demonstrated. High blood calcium levels linked to mutations of the CaSR gene lead to familial hypocalciuric hypercalcemia and the neonatal and non neonatal forms with severe hypercalcemic. Hypocalcemia determined by mutations in the CaSR gene include autosomal dominant hypocalcemia and its sporadic form. Another clinical presentation similar to Bartter syndrome has been reported. Auto-antibodies directed against CaSRs, seen in auto-immune diseases, can lead to similar clinical presentations. Finally, CaSR polymorphisms modulate the range of blood calcium levels. With diagn...
Anaerobe, 1999
Cell-free whey from a selected strain, Bifidobacterium breve C50, induced an increase in bifidoba... more Cell-free whey from a selected strain, Bifidobacterium breve C50, induced an increase in bifidobacteria associated with a Bacteroides fragilis reduction in the gut of conventional mice and humans. The purpose of our study was to investigate the mechanism of B. fragilis repression. C50 cell-free whey was given for 15 days to conventional or ex-germ-free mice mono-associated to the strain B. fragilis CFPL 358. Conventional and ex-germ-free control mice received whey which was incapable of promoting intestinal bifidobacteria and of reducing B. fragilis. Bacterial counting was carried out in the ileum, caecum and colon of both mouse models. The C50 cell-free whey induced a significant increase in endogenous bifidobacteria in the ileum of conventional mice, whereas B. fragilis was below detectable levels throughout the intestine. In ex-germ-free mice mono-associated with B. fragilis, the strain was seen to be at a high level through the whole intestine and no significant difference in counts was observed according to the whey administered to animals. The data indicated that a prerequisite for C50 cell-free whey repressive activity against B. fragilis is colonization of the mouse gut with complex bacterial microflora. With the exception of the distal ileum, the bifidobacterial overgrowth did not, however, support B. fragilis reduction. It is likely that in the caecum and colon some other bacteria participated in the process.
Pulmonary Pharmacology & Therapeutics, 2010
Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, adminis... more Aminoglycosides are broad-spectrum antibiotics with peak-dependent bactericidal activity, administered by gravity infusion or for more accuracy by electronic pump infusion. The aim of this study was to assess the difference between the two systems and its pharmacokinetic impact.