A Philippon

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (189)433.46 Total impact

  • A. Philippon
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    ABSTRACT: Les bêta-lactamases à spectre élargi ou étendu (BLSE) ont émergé peu de temps après l’introduction des céphalosporines de troisième génération (C3G). Il s’agissait dans un premier temps (1985) de pénicillinases connues (TEM/SHV) ayant modifié leur affinité pour les bêta-lactamines dont les C3G par mutation(s) (par exemple : positions 104, 164, 238, 240 pour les enzymes de type TEM). Quelques années plus tard, cette résistance, en particulier aux C3G, était en relation avec de nouvelles BLSE telles BES-1, CTX-M-1, PER-1, SFO-1, TLA-1, Toho-1, VEB-1... Cette émergence de nouveaux types ne devait plus s’arrêter avec les deux dernières : BEL-1, PME-1. Néanmoins, une véritable pandémie mondiale est maintenant observée avec la diffusion préférentielle des types CTX-M dont CTX-M-15, en particulier en milieu communautaire chez des souches de E. coli d’origine urinaire. Plus récemment, a été identifié un clone pandémique (025b:H4, ST131) pouvant associer la multirésistance aux antibiotiques à la virulence. Les BLSE se définissent comme des enzymes de la classe A transférables, donc sensibles aux inhibiteurs enzymatiques (acide clavulanique). En pratique de laboratoire, leur détection est simple d’autant que les concentrations c et C ont été récemment abaissées (≤ 1 mg/L et > 2 ou 4 mg/L) en combinant un test de synergie. Leur identification précise ne peut être que moléculaire et donc, réservée à des laboratoires spécialisés.
    No preview · Article · Oct 2013 · Immuno-analyse & Biologie Spécialisée
  • A Philippon

    No preview · Article · Oct 2012 · Pathologie Biologie
  • A Philippon · G Arlet
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    ABSTRACT: Le comportement des entérobactéries vis-à-vis de plusieurs bêta-lactamines (aminopénicillines, carboxypénicillines, céphalosporines de première génération) a permis de caractériser dans les années 1980, quatre phénotypes de résistance naturelle : G1 (sensible), G2 (pénicillinase de bas niveau), G3 (céphalosporinase) et enfin G4 (pénicillinase + céphalosporinase). Cette approche phénotypique a permis de jeter les bases de la lecture interprétative. Actuellement, l’identification de nouvelles bêta-lactamases produites par certaines espèces d’entérobactéries, moins connues des biologistes, car d’isolement moins fréquent a amené à proposer jusqu’à sept phénotypes de résistance naturelle. L’analyse, d’une part, des données publiées relatives à la sensibilité naturelle de ces entérobactéries et, d’autre part, du type de bêta-lactamase produite ou hyperproduite chez des variants isolés en clinique ou in vitro ainsi que de leurs séquences peptidiques justifie la création d’un seul nouveau groupe phénotypique, à savoir le groupe des entérobactéries naturellement productrices d’une bêta-lactamase chromosomique de type bêta-lactamase à spectre élargi/étendu (BLSE). Pour le biologiste médical, il convient aussi de connaître les possibilités de sélection de mutants résistants, en particulier aux C3G et hyperpoducteurs chez certaines espèces comme par exemple, K. oxytoca et C. amalonaticus au sein du groupe G2. Enfin, la mise en évidence d’une synergie entre l’acide clavulanique et une C3G ou l’aztréonam doit amener à impérativement différencier une entérobactérie productrice d’une BLSE plasmidique de celle seulement hyperproductrice d’une BLSE chromosomique en raison de l’impact épidémiologique très différent comme la multirésistance transférable.
    No preview · Article · Jan 2012 · Pathologie Biologie
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    ABSTRACT: Lactobacillus urinary tract infection (UTI) seems exceptionally reported. Nevertheless, with the introduction of a chromogenic medium UriSelect 4, eight cases of UTI in old women (mean of 81.2 years) mediated by Lactobacillus delbrueckii identified by DNA sequencing were reported between 2007 and 2009.
    No preview · Article · Jun 2010 · Pathologie Biologie
  • Source
    A Doloy · C Verdet · V Gautier · D Decré · E Ronco · A Hammami · A Philippon · G Arlet
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    ABSTRACT: We studied the genetic organization of blaACC-1 in 14 isolates of Enterobacteriaceae from France, Tunisia, and Germany. In a common ancestor, ISEcp1 was likely involved in the mobilization of this gene from the Hafnia alvei chromosome to a plasmid. Other genetic events involving insertion sequences (particularly IS26), transposons (particularly Tn1696), or sull-type integrons have occurred, leading to complex genetic environments. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Jan 2007 · Antimicrobial Agents and Chemotherapy
  • A. Philippon · G. Paul · M. Barthelemy · R. Labia · P. Nevot · G. Fournier · L. Gilly

    No preview · Article · Mar 2006 · FEMS Microbiology Letters
  • A Philippon · G Arlet
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    ABSTRACT: The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.
    No preview · Article · Jan 2006 · Annales de biologie clinique
  • A. Philippon · G. Arlet
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    ABSTRACT: Among gram-negative bacteria, the role of β-lactamases for natural and acquired resistance is essential and more and more complex. Numerous corresponding genes located in chromosome, plasmid, integron or CR (common region) were cloned and sequenced showing a very high diversity among this type of inactivating enzymes. A lot of genetic answers were developed by bacteria after introduction of new drugs such as β-lactam antibiotics. Such adaptability of bacterial world must lead to limit the abuse of prescriptions and a better use of drugs.
    No preview · Article · Dec 2005 · Antibiotiques
  • A. Philippon · G. Arlet
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    ABSTRACT: Among gram-negative bacteria, the role of β-lactamases for natural and acquired resistance is essential and more and more complex. Numerous corresponding genes located in chromosome, plasmid, integron or CR (common region) were cloned and sequenced showing a very high diversity among this type of inactivating enzymes. A lot of genetic answers were developed by bacteria after introduction of new drugs such as β-lactam antibiotics. Such adaptability of bacterial world must lead to limit the abuse of prescriptions and a better use of drugs.
    No preview · Article · Dec 2005 · Antibiotiques
  • Source
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    ABSTRACT: We analyzed 19 clinical isolates of the family Enterobacteriaceae (16 Escherichia coli isolates and 3 Klebsiella pneumoniae isolates) collected from four different hospitals in Paris, France, from 2000 to 2002. These strains had a particular extended-spectrum cephalosporin resistance profile characterized by a higher level of resistance to cefotaxime and aztreonam than to ceftazidime. The blaCTX-M genes encoding these β-lactamases were involved in this resistance, with a predominance of blaCTX-M-15. Ten of the 19 isolates produced both TEM-1- and CTX-M-type enzymes. One strain (E. coli TN13) expressed CMY-2, TEM-1, and CTX-M-14. blaCTX-M genes were found on large plasmids. In 15 cases the same insertion sequence, ISEcp1, was located upstream of the 5′ end of the blaCTX-M gene. In one case we identified an insertion sequence designated IS26. Examination of the other three blaCTX-M genes by cloning, sequencing, and PCR analysis revealed the presence of a complex sul1-type integron that includes open reading frame ORF513, which carries the bla gene and the surrounding DNA. Five isolates had the same plasmid DNA fingerprint, suggesting clonal dissemination of CTX-M-15-producing strains in the Paris area.
    Full-text · Article · May 2004 · Antimicrobial Agents and Chemotherapy
  • L. Prots · A. Philippon
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    ABSTRACT: Résumé Depuis plus d’une décennie, le séquençage de certains gènes bactériens est considéré comme la méthode la plus performante et la plus rapide des études taxonomiques avec la reconsidération des grands groupes et genres bactériens. L’autre critère génétique de la taxonomie est celui de l’hybridation entre ADN.
    No preview · Article · Jan 2003 · Bio Tribune Magazine
  • G. Arlet · A. Philippon

    No preview · Article · Jan 2003 · Revue Française des Laboratoires
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    ABSTRACT: Because a multiresistant K. pneumoniae outbreak detected in an intensive care unit of a parisian hospital, combined to the production of the plasmid-encoded cephalosporinase ACC-1, a probable importation via a patient was suggested from another country (Tunisia). The investigation was conducted to examine 35 clinical strains of enterobacteria resistant to ceftazidime without synergy towards Augmentin. Other test of synergy with two inhibitors, BRL 42715, Ro 48-5545 was performed by diffusion method and deposit of 10 micrograms of inhibitor on disks containing ceftazidime, cefoxitin and cefotetan. Synergies were obtained suggesting a probable production of ACC-1 type among six isolates of K. pneumoniae (two), Proteus mirabilis (one) and Salmonella (three) issued from different units. The isoelectric focusing on gel revealed at least one band of beta-lactamase activity at 7.8 but also demonstrated the simultaneous production of several probable beta-lactamases including TEM-type, SHV-2 and ACC-1 among S. enterica ser. Livingstone. The PCR of the gene blaacc-1 was positive. The sequencing (1160 pb) of two products showed high identity (99-100%) with the gene blaacc-1 deposited in 1999. Finally the ACC-1 type reported in Tunisia was probably imported in France via a patient. Because a simultaneous synthesis of ESBL and ACC-1 type, its presence may be invisible and need more investigation.
    No preview · Article · Mar 2002 · Pathologie Biologie
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    ABSTRACT: Because a multiresistant K. pneumoniae outbreak detected in an intensive care unit of a parisian hospital, combined to the production of the plasmid-encoded cephalosporinase ACC-1, a probable importation via a patient was suggested from another country (Tunisia). The investigation was conducted to examine 35 clinical strains of enterobacteria resistant to ceftazidime without synergy towards Augmentin®. Other test of synergy with two inhibitors, BRL 42715, Ro 48-5545 was performed by diffusion method and deposit of 10 μg of inhibitor on disks containing ceftazidime, cefoxitin and cefotetan. Synergies were obtained suggesting a probable production of ACC-1 type among six isolates of K. pneumoniae (two), Proteus mirabilis (one) and Salmonella (three) issued from different units. The isoelectric focusing on gel revealed at least one band of β-lactamase activity at 7.8 but also demonstrated the simultaneous production of several probable β-lactamases including TEM-type, SHV-2 and ACC-1 among S. enterica ser. Livingstone. The PCR of the gene blaacc-1 was positive. The sequencing (1160 pb) of two products showed high identity (99–100%) with the gene blaacc-1 deposited in 1999. Finally the ACC-1 type reported in Tunisia was probably imported in France via a patient. Because a simultaneous synthesis of ESBL and ACC-1 type, its presence may be invisible and need more investigation.
    No preview · Article · Jan 2002 · Pathologie Biologie
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    G Arlet · D Nadjar · J L Herrmann · J L Donay · P H Lagrange · A Philippon

    Full-text · Article · Nov 2001 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: A multicenter study was carried out to evaluate the performance of a new commercial automated system in comparison with that of the reference agar dilution method. Ten clinical microbiology laboratories tested a collection of 61 strains of gram-negative bacilli (49 Enterobacteriaceae and 12 Pseudomonas aeruginosa), and 6 other laboratories tested a collection of 55 strains of gram-positive cocci (10 enterococci and 45 staphylococci) against 10-20 antimicrobial agents. The strains were selected on the basis that they harbored challenging and characterized mechanisms of resistance. In comparison with the agar reference method, the automated system gave an overall essential agreement (+/-1 dilution) of 94.5%, 93.5%, and 97% for the gram-negative bacilli, enterococci, and staphylococci, respectively. According to the interpretive standards of the National Committee for Clinical Laboratory Standards, the category agreement ranged from 96 to 96.4% for the three sets of organisms. The accuracy of the automated system, as determined by the kappa test, ranged from 0.80 to 0.88, reflecting an almost perfect agreement with the reference technique. Very major, major, and minor errors obtained with the automated system were 0.3%, 2.9%, and 6.6% for gram-negative bacilli, 3.4%, 0%, and 5% for enterococci, and 1%, 1.6%, and 2.7% for staphylococci, respectively. The high rate of very major errors in enterococci was mostly due to a single strain of multidrug-resistant Enterococcus faecium, which was found susceptible to several antibiotics in a majority of participant laboratories. The use of a heavy inoculum and of a broth test medium by the automated system might account for a better expression of certain resistance mechanisms, including beta-lactamases, as compared to the agar dilution reference method. The interlaboratory reproducibility was acceptable, as shown by the narrow dispersion of MICs and by the results of quality control.
    No preview · Article · Oct 2001 · European Journal of Clinical Microbiology

  • No preview · Article · Dec 2000 · Pathologie Biologie
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    ABSTRACT: Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.
    No preview · Article · Jul 2000 · FEMS Microbiology Letters

  • No preview · Article · Jan 2000 · Médecine et Maladies Infectieuses
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    ABSTRACT: Observation Nous avons isolé une souche de Proteus mirabilis multirésistante aux β-lactamines (y compris la céfoxitine), à partir d'un prélèvement urinaire chez une femme hospitalisée. Le profil de sensibilité aux β-lactamines était identique à celui constaté à la suite de la sécrétion de céphalosporinase. Ce caractère de résistance aux β-lactamines a été transféré par conjugaison à E. coli K12. Enfin, la PCR utilisant les amorces consensus de AmpC dérivées du gène correspondant de C. freundii et E. cloacae a montré une amplification positive. Case Report A clinical strain of P. mirabilis multiresistant to β-lactams (including cefoxitin) was isolated from an urinary tract infection in a hospitalized woman. The susceptibility pattern to β-lactams was similar to the usual profile mediated by the synthesis of cephalosporinase. This pattern of resistance to β-lactams was transferred by conjugation to E. coli K12. Finally, PCR with the consensus primers of the Citrobacter freundii and Enterobacter cloacae AmpC β-lactamase gene showed a positive amplification. Conclusion It is strongly suggested that this profile of resistance was related to the synthesis of AmpC type β-lactamase encoded on the plasmid.
    No preview · Article · Jun 1999 · Médecine et Maladies Infectieuses

Publication Stats

4k Citations
433.46 Total Impact Points

Institutions

  • 1984-2013
    • Université René Descartes - Paris 5
      • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 1997
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 1996
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1995
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1989-1995
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Faculty of Medecine of Tunis
      Tunis-Ville, Tūnis, Tunisia
  • 1988-1993
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 1991
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 1989-1991
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Île-de-France, France
  • 1988-1990
    • Hôpital Charles-Nicolle
      Tunis-Ville, Tūnis, Tunisia