E. Heinz, The return of Pfeiffer's bacillus: Rising incidence of ampicillin resistance in Haemophilus influenzae, Microb Genom [Internet]. 12 sept, vol.4, issue.9, 2018.

M. Kilian, A taxonomic study of the genus Haemophilus, with the proposal of a new species, J Gen Microbiol. mars, vol.93, issue.1, pp.9-62, 1976.

V. Cattoir, O. Lemenand, A. Gaillot, and O. , The sodA gene as a target for phylogenetic dissection of the genus Haemophilus and accurate identification of human clinical isolates, International Journal of Medical Microbiology. 4 déc, vol.296, issue.8, pp.531-571, 2006.

M. Pittman, Variation and type specificity in the bacterial species hemophilus influenzae, J Exp Med. 31 mars, vol.53, issue.4, pp.471-92, 1931.

P. King, Haemophilus influenzae and the lung (Haemophilus and the lung), Clin Transl Med. 14 juin, vol.1, p.10, 2012.

H. Influenzae, Invasive Disease | 2015 Case Definition, 2015.

E. R. Moxon and K. A. Vaughn, The type b capsular polysaccharide as a virulence determinant of Haemophilus influenzae: studies using clinical isolates and laboratory transformants, J Infect Dis. avr, vol.143, issue.4, pp.517-541, 1981.

V. Nizet, K. F. Colina, J. R. Almquist, C. E. Rubens, and A. L. Smith, A virulent nonencapsulated Haemophilus influenzae, J Infect Dis. janv, vol.173, issue.1, pp.180-186, 1996.

B. L. Duell, Y. Su, and K. Riesbeck, Host-pathogen interactions of nontypeable Haemophilus influenzae: from commensal to pathogen, FEBS Lett, vol.590, issue.21, pp.3840-53, 2016.

J. Van-eldere, M. Slack, S. Ladhani, and A. W. Cripps, Non-typeable Haemophilus influenzae, an under-recognised pathogen, Lancet Infect Dis. déc, vol.14, issue.12, pp.1281-92, 2014.

M. Cerquetti and M. Giufrè, Why we need a vaccine for non-typeable Haemophilus influenzae, Hum Vaccin Immunother, vol.12, issue.9, pp.2357-61, 2016.

J. D. Langereis and M. I. De-jonge, Invasive Disease Caused by Nontypeable Haemophilus influenzae. Emerging Infect Dis, vol.21, pp.1711-1719, 2015.

, Otitis media in infancy and intellectual ability, school achievement, speech, and language at age 7 years. Greater Boston Otitis Media Study Group

H. C. Smith-vaughan, K. S. Sriprakash, J. D. Mathews, and D. J. Kemp, Nonencapsulated Haemophilus influenzae in Aboriginal infants with otitis media: prolonged carriage of P2 porin variants and evidence for horizontal P2 gene transfer, Infect Immun. avr, vol.65, issue.4, pp.1468-74, 1997.

D. W. Teele, J. O. Klein, and B. Rosner, Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study, J Infect Dis. juill, vol.160, issue.1, pp.83-94, 1989.

P. S. Morris, A. J. Leach, P. Silberberg, G. Mellon, C. Wilson et al., Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross-sectional survey, BMC Pediatr. 20 juill, vol.5, p.27, 2005.

, Genomic sequence of an otitis media isolate of nontypeable Haemophilus influenzae: comparative study with H. influenzae serotype d, strain KW20

S. J. Barenkamp and E. Leininger, Cloning, expression, and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surfaceexposed proteins related to filamentous hemagglutinin of Bordetella pertussis, Infect Immun. avr, vol.60, issue.4, pp.1302-1315, 1992.

K. Shen, P. Antalis, J. Gladitz, S. Sayeed, A. Ahmed et al., Identification, distribution, and expression of novel genes in 10 clinical isolates of nontypeable Haemophilus influenzae, Infect Immun. juin, vol.73, issue.6, pp.3479-91, 2005.

Y. Harabuchi, H. Faden, N. Yamanaka, L. Duffy, J. Wolf et al., Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics, J Infect Dis, vol.170, issue.4, pp.862-868, 1994.

T. F. Murphy and M. A. Apicella, Nontypable Haemophilus influenzae: a review of clinical aspects, surface antigens, and the human immune response to infection, Rev Infect Dis. févr, vol.9, issue.1, pp.1-15, 1987.

, Progress towards a vaccine for nontypable Haemophilus influenzae. -PubMed -NCBI

T. F. Murphy and S. Sethi, Bacterial infection in chronic obstructive pulmonary disease, Am Rev Respir Dis, vol.146, issue.4, pp.1067-83, 1992.

A. R. Foxwell, J. M. Kyd, and A. W. Cripps, Nontypeable Haemophilus influenzae: Pathogenesis and Prevention, Microbiol Mol Biol Rev. juin, vol.62, issue.2, pp.294-308, 1998.

S. Collins, D. J. Litt, S. Flynn, M. E. Ramsay, M. Slack et al., Neonatal invasive Haemophilus influenzae disease in England and Wales: epidemiology, clinical characteristics, and outcome, Clin Infect Dis. 15 juin, vol.60, issue.12, pp.1786-92, 2015.

M. Giufrè, R. Cardines, M. Accogli, and M. Cerquetti, Neonatal Invasive Haemophilus influenzae Disease and Genotypic Characterization of the Associated Strains in Italy, Clin Infect Dis, vol.61, issue.7, pp.1203-1207, 2015.

R. J. Wallace, C. J. Baker, F. J. Quinones, D. G. Hollis, R. E. Weaver et al., Nontypable Haemophilus influenzae (biotype 4) as a neonatal, maternal, and genital pathogen, Rev Infect Dis. févr, vol.5, issue.1, pp.123-159, 1983.

M. S. Reddy, T. F. Murphy, H. S. Faden, and J. M. Bernstein, Middle ear mucin glycoprotein: purification and interaction with nontypable Haemophilus influenzae and Moraxella catarrhalis, Otolaryngol Head Neck Surg. févr, vol.116, issue.2, pp.175-80, 1997.

N. Miyamoto and L. O. Bakaletz, Selective adherence of non-typeable Haemophilus influenzae (NTHi) to mucus or epithelial cells in the chinchilla eustachian tube and middle ear. Microb Pathog, vol.21, pp.343-56, 1996.

F. W. Denny, Effect of a toxin produced by Haemophilus influenzae on ciliated respiratory epithelium, J Infect Dis. févr, vol.129, issue.2, pp.93-100, 1974.

H. Janson, A. Carl-n-b,-cervin, A. Forsgren, A. B. Magnusdottir, and S. Lindberg, Effects on the ciliated epithelium of protein D-producing and -nonproducing nontypeable Haemophilus influenzae in nasopharyngeal tissue cultures, J Infect Dis. sept, vol.180, issue.3, pp.737-783, 1999.

C. A. Rodriguez, V. Avadhanula, A. Buscher, A. L. Smith, . St et al., Prevalence and Distribution of Adhesins in Invasive Non-Type b Encapsulated Haemophilus influenzae, Infect Immun. avr, vol.71, issue.4, pp.1635-1677, 2003.

S. J. Barenkamp and F. F. Bodor, Development of serum bactericidal activity following nontypable Haemophilus influenzae acute otitis media, Pediatr Infect Dis J. mai, vol.9, issue.5, pp.333-342, 1990.

J. W. St-geme, S. Falkow, and S. J. Barenkamp, High-molecular-weight proteins of nontypable Haemophilus influenzae mediate attachment to human epithelial cells, Proc Natl Acad Sci USA. 1 avr, vol.90, issue.7, pp.2875-2884, 1993.

J. W. St-geme, J. S. Pinkner, G. P. Krasan, J. Heuser, E. Bullitt et al., Haemophilus influenzae pili are composite structures assembled via the HifB chaperone, Proc Natl Acad Sci, vol.93, issue.21, pp.11913-11921, 1996.

S. M. Van-ham, L. Van-alphen, F. R. Mooi, and J. P. Van-putten, The fimbrial gene cluster of Haemophilus influenzae type b, Mol Microbiol. août, vol.13, issue.4, pp.673-84, 1994.

K. W. Mccrea, W. J. Watson, J. R. Gilsdorf, and C. F. Marrs, Identification of hifD and hifE in the pilus gene cluster of Haemophilus influenzae type b strain Eagan. Infect Immun, vol.62, pp.4922-4930, 1994.

G. P. Krasan, D. Cutter, S. L. Block, and J. W. St-geme, Adhesin expression in matched nasopharyngeal and middle ear isolates of nontypeable Haemophilus influenzae from children with acute otitis media, Infect Immun. janv, vol.67, issue.1, pp.449-54, 1999.

, Identification of a second family of high-molecular-weight adhesion proteins expressed by non-typable Haemophilus influenzae

M. H. Mulks, S. J. Kornfeld, B. Frangione, and A. G. Plaut, Relationship between the specificity of IgA proteases and serotypes in Haemophilus influenzae, J Infect Dis. août, vol.146, issue.2, pp.266-74, 1982.

A. G. Plaut, The IgA1 proteases of pathogenic bacteria, Annu Rev Microbiol, vol.37, pp.603-625, 1983.

S. West-barnette, A. Rockel, and W. E. Swords, Biofilm growth increases phosphorylcholine content and decreases potency of nontypeable Haemophilus influenzae endotoxins, Infect Immun. mars, vol.74, issue.3, pp.1828-1864, 2006.

T. D. Starner, N. Zhang, G. Kim, M. A. Apicella, and P. B. Mccray, Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis, Am J Respir Crit Care Med. 15 juill, vol.174, issue.2, pp.213-233, 2006.

S. M. Van-ham, L. Van-alphen, F. R. Mooi, and J. P. Van-putten, Phase variation of H. influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region, Cell. 18 juin, vol.73, issue.6, pp.1187-96, 1993.

B. Duim, L. Vogel, W. Puijk, H. M. Jansen, R. H. Meloen et al., Fine mapping of outer membrane protein P2 antigenic sites which vary during persistent infection by Haemophilus influenzae, Infect Immun, vol.64, issue.11, pp.4673-4682, 1996.

, Prevalence of the hifBC, hmw1A, hmw2A, hmwC, and hia Genes in Haemophilus influenzae Isolates

D. Sur,

J. Xie, P. C. Juliao, J. R. Gilsdorf, D. Ghosh, M. Patel et al., Identification of new genetic regions more prevalent in nontypeable Haemophilus influenzae otitis media strains than in throat strains, J Clin Microbiol. déc, vol.44, issue.12, pp.4316-4341, 2006.

M. Rachidi, F. A. Moussair, N. Daoudi, and N. Soraa, Méningite à Haemophilus influenzae de type non b chez un nourrisson: cause rare à pronostic réservé, Pan Afr Med J [Internet, vol.22, 2018.

, Clinical Microbiology Procedures Handbook, Fourth Edition, Clinical Microbiology Procedures Handbook, 2016.

, Manual of Clinical Microbiology, Eleventh Edition. American Society of Microbiology, Manual of Clinical Microbiology, 2015.

D. Sur,

A. E. Clark, E. J. Kaleta, A. Arora, and D. M. Wolk, Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry: a Fundamental Shift in the Routine Practice of Clinical Microbiology, Clin Microbiol Rev. juill, vol.26, issue.3, pp.547-603, 2013.

M. J. Binks, B. Temple, L. Kirkham, S. P. Wiertsema, E. M. Dunne et al., Molecular Surveillance of True Nontypeable Haemophilus influenzae: An Evaluation of PCR Screening Assays, Disponible sur, vol.7

X. Wang, R. Mair, C. Hatcher, M. J. Theodore, K. Edmond et al., Detection of bacterial pathogens in Mongolia meningitis surveillance with a new real-time PCR assay to detect Haemophilus influenzae, International Journal of Medical Microbiology. 1 avr, vol.301, issue.4, pp.303-312, 2011.

C. E. Corless, M. Guiver, R. Borrow, V. Edwards-jones, A. J. Fox et al., Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using realtime PCR, J Clin Microbiol. avr, vol.39, issue.4, pp.1553-1561, 2001.

K. W. Mccrea, J. Xie, N. Lacross, M. Patel, D. Mukundan et al., Relationships of nontypeable Haemophilus influenzae strains to hemolytic and nonhemolytic Haemophilus haemolyticus strains, J Clin Microbiol. févr, vol.46, issue.2, pp.406-422, 2008.

N. Nørskov-lauritsen, M. D. Overballe, and M. Kilian, Delineation of the species Haemophilus influenzae by phenotype, multilocus sequence phylogeny, and detection of marker genes, J Bacteriol. févr, vol.191, issue.3, pp.822-853, 2009.

J. J. Harper and M. H. Tilse, Biotypes of Haemophilus influenzae that are associated with noninvasive infections, J Clin Microbiol, vol.29, issue.11, pp.2539-2581, 1991.

F. Denis, Bactériologie médicale, vol.599, 2016.

T. J. Falla, E. C. Anderson, M. M. Chappell, M. P. Slack, and D. W. Crook, Cross-reaction of spontaneous capsule-deficient Haemophilus influenzae type b mutants with typespecific antisera, Eur J Clin Microbiol Infect Dis. févr, vol.12, issue.2, pp.147-155, 1993.

S. Wen, D. Feng, D. Chen, L. Yang, and Z. Xu, Molecular epidemiology and evolution of Haemophilus influenzae. Infection, Genetics and Evolution. 1 juin, vol.80, p.104205, 2020.

C. C. Potts, N. Topaz, L. D. Rodriguez-rivera, F. Hu, H. Chang et al., Genomic characterization of Haemophilus influenzae: a focus on the capsule locus, BMC Genomics, vol.20, issue.12, 2019.

A. Marty, O. Greiner, P. Day, S. Gunziger, K. Mühlemann et al., Detection of Haemophilus influenzae Type b by Real-Time PCR, J Clin Microbiol. août, vol.42, issue.8, pp.3813-3818, 2004.

E. Meats, E. J. Feil, S. Stringer, A. J. Cody, R. Goldstein et al., Characterization of Encapsulated and Noncapsulated Haemophilus influenzae and Determination of Phylogenetic Relationships by Multilocus Sequence Typing, J Clin Microbiol. avr, vol.41, issue.4, pp.1623-1659, 2003.

V. Månsson, J. R. Gilsdorf, G. Kahlmeter, M. Kilian, J. S. Kroll et al., Capsule Typing of Haemophilus influenzae by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry1, Emerg Infect Dis. mars, vol.24, issue.3, pp.443-52, 2018.

A. Benítez-páez, K. J. Portune, and Y. Sanz, Species-level resolution of 16S rRNA gene amplicons sequenced through the MinION TM portable nanopore sequencer, vol.28

J. Moon, Y. Jang, N. Kim, W. B. Park, K. Park et al., Diagnosis of Haemophilus influenzae Pneumonia by Nanopore 16S Amplicon Sequencing of Sputum, Emerg Infect Dis. oct, vol.24, issue.10, pp.1944-1950, 2018.

K. M. Pendleton, J. R. Erb-downward, Y. Bao, W. R. Branton, N. R. Falkowski et al., Rapid Pathogen Identification in Bacterial Pneumonia Using Real-Time Metagenomics, Am J Respir Crit Care Med, vol.15, issue.12, pp.1610-1612, 2017.

, Antimicrobial resistance in Haemophilus influenzae. -PubMed -NCBI

J. T. Park and J. L. Strominger, Mode of action of penicillin, Science. 18 janv, vol.125, issue.3238, pp.99-101, 1957.

, Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery

K. Poole, Resistance to beta-lactam antibiotics, Cell Mol Life Sci. sept, vol.61, issue.17, pp.2200-2223, 2004.

H. Wilson and M. E. Török, Extended-spectrum ?-lactamase-producing and carbapenemase-producing Enterobacteriaceae, Microb Genom, vol.4, issue.7, 2018.

A. W. Mathies, Penicillins in the treatment of bacterial meningitis, J R Coll Physicians Lond. janv, vol.6, issue.2, pp.139-185, 1972.

N. I. Leaves, I. Dimopoulou, I. Hayes, S. Kerridge, T. Falla et al., Epidemiological studies of large resistance plasmids in Haemophilus, J Antimicrob Chemother. mai, vol.45, issue.5, pp.599-604, 2000.

C. Fleury, F. Resman, J. Rau, and K. Riesbeck, Prevalence, distribution and transfer of small ?-lactamase-containing plasmids in Swedish Haemophilus influenzae, J Antimicrob Chemother. mai, vol.69, issue.5, pp.1238-1280, 2014.

, First characterization of heterogeneous resistance to imipenem in invasive nontypeable Haemophilus influenzae isolates

F. S. Kaczmarek, T. D. Gootz, F. Dib-hajj, W. Shang, S. Hallowell et al., Genetic and molecular characterization of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin, Antimicrob Agents Chemother. mai, vol.48, issue.5, pp.1630-1639, 2004.

, Ampicillin-resistant non-beta-lactamase-producing Haemophilus influenzae in Spain: recent emergence of clonal isolates with increased resistance to

, Association of amino acid substitutions in penicillin-binding protein 3 with betalactam resistance in beta-lactamase-negative ampicillin-resistant, PubMed -NCBI

M. Peric, B. Bozdogan, M. R. Jacobs, and P. C. Appelbaum, Effects of an efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates, Antimicrob Agents Chemother. mars, vol.47, issue.3, pp.1017-1039, 2003.

T. Bogdanovich, B. Bozdogan, and P. C. Appelbaum, Effect of efflux on telithromycin and macrolide susceptibility in Haemophilus influenzae, Antimicrob Agents Chemother. mars, vol.50, issue.3, pp.893-901, 2006.

S. Seyama, T. Wajima, H. Nakaminami, and N. Noguchi, Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae, Antimicrob Agents Chemother, issue.11, p.61, 2017.

S. Seyama, T. Wajima, Y. Yanagisawa, H. Nakaminami, M. Ushio et al., Rise in Haemophilus influenzae With Reduced Quinolone Susceptibility and Development of a Simple Screening Method, Pediatr Infect Dis J, vol.36, issue.3, pp.263-269, 2017.

H. Kondo, S. Ito, K. Hatazaki, K. Horie, K. Nakane et al., GyrA and/or ParC alterations of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis, J Infect Chemother. mars, vol.24, issue.3, pp.232-237, 2018.

S. Kuo, P. Chen, Y. Shiau, H. Wang, J. Lai et al., Levofloxacinresistant haemophilus influenzae, Emerging Infect Dis. août, vol.20, issue.8, pp.1386-90, 2004.

C. Puig, J. M. Tirado-vélez, L. Calatayud, F. Tubau, J. Garmendia et al., Molecular characterization of fluoroquinolone resistance in nontypeable Haemophilus influenzae clinical isolates, Antimicrob Agents Chemother. janv, vol.59, issue.1, pp.461-467, 2015.

, Coevolution of DNA uptake sequences and bacterial proteomes. -PubMed -NCBI

H. O. Smith, M. L. Gwinn, and S. L. Salzberg, DNA uptake signal sequences in naturally transformable bacteria, Res Microbiol. déc, vol.150, issue.9, pp.603-619, 1999.

, DNA uptake during bacterial transformation. -PubMed -NCBI

E. A. Witherden, M. P. Bajanca-lavado, S. G. Tristram, and A. Nunes, Role of inter-species recombination of the ftsI gene in the dissemination of altered penicillin-bindingprotein-3-mediated resistance in Haemophilus influenzae and Haemophilus haemolyticus, J Antimicrob Chemother. juin, vol.69, issue.6, pp.1501-1510, 2014.

D. Skaare, I. L. Anthonisen, D. A. Caugant, A. Jenkins, M. Steinbakk et al., Multilocus sequence typing and ftsI sequencing: a powerful tool for surveillance of penicillin-binding protein 3-mediated beta-lactam resistance in nontypeable Haemophilus influenzae, BMC Microbiol. 20 mai, vol.14, p.131, 2014.

M. Lipsitch and G. R. Siber, How Can Vaccines Contribute to Solving the Antimicrobial Resistance Problem? mBio, 07, vol.7, issue.3, 2016.

, The rise and fall of pneumococcal serotypes carried in the PCV era

H. Goto, K. Shimada, H. Ikemoto, and T. Oguri, Study Group on Antimicrobial Susceptibility of Pathogens Isolated from Respiratory Infections. Antimicrobial susceptibility of pathogens isolated from more than 10,000 patients with infectious respiratory diseases: a 25-year longitudinal study, J Infect Chemother. déc, vol.15, issue.6, pp.347-60, 2009.

, Moraxella catarrhalis outer membrane vesicles carry ?-lactamase and promote survival of Streptococcus pneumoniae and Haemophilus influenzae by inac

A. C. Perez and T. F. Murphy, Potential impact of a Moraxella catarrhalis vaccine in COPD, Vaccine. 3 sept, vol.37, issue.37, pp.5551-5559, 2019.

V. Schaar, I. Uddbäck, T. Nordström, and K. Riesbeck, Group A streptococci are protected from amoxicillin-mediated killing by vesicles containing ?-lactamase derived from Haemophilus influenzae, J Antimicrob Chemother. janv, vol.69, issue.1, pp.117-137, 2014.

, The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respirator

D. Felmingham and R. N. Grüneberg, The Alexander Project 1996-1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections, J Antimicrob Chemother. févr, vol.45, issue.2, pp.191-203, 2000.

A. R. Barbosa, M. Giufrè, M. Cerquetti, and M. P. Bajanca-lavado, Polymorphism in ftsI gene and {beta}-lactam susceptibility in Portuguese Haemophilus influenzae strains: clonal dissemination of beta-lactamase-positive isolates with decreased susceptibility to amoxicillin/clavulanic acid, J Antimicrob Chemother. avr, vol.66, issue.4, pp.788-96, 2011.

H. Honda, T. Sato, M. Shinagawa, Y. Fukushima, C. Nakajima et al., Multiclonal Expansion and High Prevalence of ?-Lactamase-Negative Haemophilus influenzae with High-Level Ampicillin Resistance in Japan and Susceptibility to Quinolones, Antimicrob Agents Chemother, vol.62, issue.9, 2018.

K. Hasegawa, K. Yamamoto, N. Chiba, R. Kobayashi, K. Nagai et al., Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States, Microb Drug Resist, vol.9, issue.1, pp.39-46, 2003.

M. Giufrè, L. Daprai, R. Cardines, P. Bernaschi, L. Ravà et al., Carriage of Haemophilus influenzae in the oropharynx of young children and molecular epidemiology of the isolates after fifteen years of H. influenzae type b vaccination in Italy. Vaccine, vol.33, pp.6227-6261, 2015.

A. Deghmane, H. E. Chehboub, S. Terrade, A. Falguières, M. Sort et al., High diversity of invasive Haemophilus influenzae isolates in France and the emergence of resistance to third generation cephalosporins by alteration of ftsI gene, J Infect, vol.79, issue.1, pp.7-14, 2019.
URL : https://hal.archives-ouvertes.fr/pasteur-02423493

D. Sur,

D. M. Nitta, M. A. Jackson, V. F. Burry, and L. C. Olson, Invasive Haemophilus influenzae type f disease, Pediatr Infect Dis J. févr, vol.14, issue.2, pp.157-60, 1995.

M. Ulanova and R. Tsang, Haemophilus influenzae serotype a as a cause of serious invasive infections, Lancet Infect Dis. janv, vol.14, issue.1, pp.70-82, 2014.

S. Desai, F. B. Jamieson, S. N. Patel, C. Y. Seo, V. Dang et al., The Epidemiology of Invasive Haemophilus influenzae Non-Serotype B Disease in Ontario, PLoS One, vol.10, issue.16, 2004.

D. Sur,

L. J. Finney, A. Ritchie, E. Pollard, S. L. Johnston, and P. Mallia, Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae, Int J Chron Obstruct Pulmon Dis, vol.9, pp.1119-1151, 2014.

R. Dagan and E. Leibovitz, Bacterial eradication in the treatment of otitis media, Lancet Infect Dis, vol.2, issue.10, pp.593-604, 2002.

A. R. Foxwell, J. M. Kyd, and A. W. Cripps, Nontypeable Haemophilus influenzae: Pathogenesis and Prevention, Microbiol Mol Biol Rev. juin, vol.62, issue.2, pp.294-308, 1998.

, Oral immunisation with killed Haemophilus influenzae for protection against acute bronchitis in chronic obstructive lung disease

R. L. Clancy, A. W. Cripps, A. J. Husband, and D. Buckley, Specific immune response in the respiratory tract after administration of an oral polyvalent bacterial vaccine, Infect Immun. févr, vol.39, issue.2, pp.491-497, 1983.

D. Lehmann, K. J. Coakley, C. A. Coakley, V. Spooner, J. M. Montgomery et al., Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea, Am Rev Respir Dis. août, vol.144, issue.2, pp.324-354, 1991.

M. K. Tandon and V. Gebski, A controlled trial of a killed Haemophilus influenzae vaccine for prevention of acute exacerbations of chronic bronchitis, Aust N Z J Med. août, vol.21, issue.4, pp.427-459, 1991.

, amending Decision 2002/253/EC laying down case definitions for reporting communicable diseases to the Community network under Decision No 2119/98/EC of the European Parliament and of the Council, 2012.

P. Seng, J. Rolain, P. E. Fournier, L. Scola, B. Drancourt et al., MALDI-TOFmass spectrometry applications in clinical microbiology, Future Microbiol, vol.5, issue.11, pp.1733-54, 2010.

. Openepi,

D. Sur,

M. Hotomi, A. Togawa, M. Kono, G. Sugita, R. Sugita et al., An Application of Outer Membrane Protein P6-Specific Enzyme-Linked Immunosorbent Assay for Detection of Haemophilus influenzae in Middle Ear Fluids and Nasopharyngeal Secretions, Disponible sur, vol.8

S. Ladhani, M. Slack, P. T. Heath, A. Von-gottberg, M. Chandra et al., Invasive Haemophilus influenzae Disease, vol.16, issue.3, pp.455-63, 1996.

T. F. Murphy, Respiratory infections caused by non-typeable Haemophilus influenzae, Curr Opin Infect Dis. avr, vol.16, issue.2, pp.129-163, 2003.

B. Haemophilus-influenzae and . Igg,

D. Sur,

J. Descy, C. Meex, P. Melin, M. Hayette, H. Pascale et al., Spectrométrie de masse MALDI-TOF en bactériologie clinique ou comment identifier une bactérie en une minute, Revue médicale de Liège. 1 janv, p.65, 2010.

K. Montgomery, R. L. Drew, and W. L. , Chromogenic cephalosporin spot test to detect beta-lactamase in clinically significant bacteria, J Clin Microbiol. févr, vol.9, issue.2, pp.205-212, 1979.

A. Skinner and R. Wise, A comparison of three rapid methods for the detection of betalactamase activity in Haemophilus influenzae, J Clin Pathol, vol.30, issue.11, pp.1030-1032, 1977.

C. H. O'callaghan, A. Morris, S. M. Kirby, and A. H. Shingler, Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate, Antimicrob Agents Chemother. avr, vol.1, issue.4, pp.283-291, 1972.

, FilmArray Respiratory Panel 2 plus (RP2 plus)

F. Biomérieux,

, Request a Free Demo

B. Diagnostics,

, MinION: A Portable, Real-Time DNA/RNA Sequencing Device

B. A. Claesson, T. Lagergård, and B. Trollfors, Development of serum antibodies of the immunoglobulin G class and subclasses against the capsular polysaccharide of Haemophilus influenzae type b in children and adults with invasive infections, J Clin Microbiol. déc, vol.26, issue.12, pp.2549-53, 1988.

H. Käyhty, H. Jousimies-somer, H. Peltola, and P. H. Mäketä, Antibody response to capsular polysaccharides of groups A and C neisseria meningitidis and Haemophilus influenzae type b during bacteremic disease, J Infect Dis. janv, vol.143, issue.1, pp.32-41, 1981.

H. Käyhty, H. Peltola, V. Karanko, and P. H. Mäkelä, Test à la Céfinase Certaines bactéries (Staphylococcus, Enterococcus, Haemophilus influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis et germes anaérobies) ont la propriété de produire des enzymes capables d, J Infect Dis. juin, vol.147, issue.6, p.1100, 1983.

, La production de ces enzymes est donc très souvent le signe d'une résistance aux ?lactamines

, L'utilisation de ce test permet d'indiquer la présence d'une ?-lactamase ou non. Un test positif s'observe par la coloration du papier en rose. Cette coloration correspond à l'ouverture du cycle ?-lactame de la céphalosporine chromogénique grâce à l'action de la ?-lactamase. La présence de cette enzyme inactive l'action de l'amoxicilline qui est l'une des molécules de première ligne utilisée en thérapeutique. La PCR Polymerase Chain Reaction ou PCR est une méthode d'amplification d'acides nucléiques in vitro permettant d'augmenter la quantité de matériel génétique d'intérêt. Cette méthode permet d'obtenir à partir d'un échantillon peu abondant, qui libère un composé rouge lors de son hydrolyse par une ?-lactamase

, Pour ce faire, dans le milieu réactionnel ou mix, on a besoin de la matrice d'ADN d'intérêt, de l'ADN polymérase (Taq-polymérase), de tampon (MgCl 2, stabilisant la liaison ADN pol/ADN matrice), dNTPs (désoxyribonucléotides, en excès), La PCR fait appel à une succession de réactions de réplication d'une matrice d'ADN double brins

, Afin de réaliser les différentes étapes de PCR, il est indispensable d'utiliser un thermocycleur qui permet de faire varier la température lors de la réaction. Premièrement, on a une dénaturation de l'ADN (95 °C) : les liaisons hydrogènes du double brin d'ADN sont lysées et on obtient deux brins d'ADN

, °C) correspond à l'appariement des bases complémentaires entre les amorces et l'ADN

, durant laquelle les amorces hybridées à la matrice servent de point de départ à la polymérisation du brin d'ADN de façon complémentaire et antiparallèle. L'élongation se fait de l'extrémité 5' vers 3'. On a une croissance exponentielle de notre matériel de départ. Ce cycle composé de trois étapes se répète jusqu'à épuisement du matériel présent dans le mix

, correspond à la détection du matériel amplifié au fur et à mesure des cycles d'amplification. Ce principe se base sur l'utilisation de : dNTPs, MgCl, Taqpol, amorces spécifiques et des molécules fluorescentes (soit des sondes spécifiques marquées, soit un agent intercalant). A la différence de la PCR classique, la qPCR permet de quantifier l'ADN initial. Pour cela, Une méthode de PCR en temps réel (qPCR)

, Haemophilus influenzae (Hinf) était connu pour provoquer des infections invasives et non invasives. La mise en place de la vaccination contre Haemophilus influenzae de sérogroupe b, qui était le sérotype dominant, a permis une éradication quasitotale de ce dernier. Néanmoins, l'épidémiologie d'Hinf a connu de profondes modifications avec une augmentation du nombre d

, Mille-six-cent-vingt-trois infections ont été documentées durant cette période. Nous avons mis en évidence une saisonnalité dans l'évolution des infections à Hinf avec une prédominance en hiver. Au sein de ces dernières, Nous avons mené une étude rétrospective des infections à Hinf diagnostiquées à l'AP-HM de, 2014.

, La mortalité globale des infections invasives de notre étude est de l'ordre de 10% et touche en particulier les plus de 60 ans avec une mortalité atteignant 21,4 %. Nous avons typé 19 % des souches (310/1623)

, 7 % étaient sauvages et une seule était résistante aux céphalosporines de 3 ème génération. Le mécanisme de résistance aux ?-lactamines le plus fréquent est l'acquisition d'une ?-lactamase, vol.74

, Devant l'augmentation du nombre d'infections et de résistances, il est indispensable de trouver de nouvelles armes afin de prévenir ces infections, p.60

. Mots-clés, Haemophilus influenzae