title: Molecular epidemiology of nontypeable Haemophilus influenzae causing community-acquired pneumonia in adults.
abstract: Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen which causes a variety of respiratory infections. The objectives of the study were to determine its antimicrobial susceptibility, to characterize the β-lactam resistance, and to establish a genetic characterization of NTHi isolates. Ninety-five NTHi isolates were analyzed by pulsed field gel electrophoresis (PFGE) and multi locus sequence typing (MLST). Antimicrobial susceptibility was determined by microdilution, and the ftsI gene (encoding penicillin-binding protein 3, PBP3) was PCR amplified and sequenced. Thirty (31.6%) isolates were non-susceptible to ampicillin (MIC ≥ 2 mg/L), with 10 of them producing β-lactamase type TEM-1 as a resistance mechanism. After ftsI sequencing, 39 (41.1%) isolates showed amino acid substitutions in PBP3, with Asn526 → Lys being the most common (69.2%). Eighty-four patients were successfully treated with amoxicillin/clavulanic acid, ceftriaxone and levofloxacin. Eight patients died due either to aspiration or complication of their comorbidities. In conclusion, NTHi causing CAP in adults shows high genetic diversity and is associated with a high rate of reduced susceptibility to ampicillin due to alterations in PBP3. The analysis of treatment and outcomes demonstrated that NTHi strains with mutations in the ftsI gene could be successfully treated with ceftriaxone or fluoroquinolones.
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, Barcelona, Spain ; CIBER de Enfermedades Respiratorias (CIBERes), ISCIII, Madrid, Spain ; Epidemiology of Bacterial Infections Group, IDIBELL, Barcelona, Spain ; Department of Pathology and Experimental Therapeutics, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Puig
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, Barcelona, Spain ; CIBER de Enfermedades Respiratorias (CIBERes), ISCIII, Madrid, Spain ; Epidemiology of Bacterial Infections Group, IDIBELL, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Calatayud
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, Barcelona, Spain ; CIBER de Enfermedades Respiratorias (CIBERes), ISCIII, Madrid, Spain ; Epidemiology of Bacterial Infections Group, IDIBELL, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Martí
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, Barcelona, Spain ; CIBER de Enfermedades Respiratorias (CIBERes), ISCIII, Madrid, Spain.
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Department of Infectious Diseases, Hospital Universitari de Bellvitge, Barcelona, Spain ; Spanish Network for Research on Infectious Diseases (REIPI), ISCIII, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Garcia-Vidal
authors.affiliation: Department of Infectious Diseases, Hospital Universitari de Bellvitge, Barcelona, Spain ; Spanish Network for Research on Infectious Diseases (REIPI), ISCIII, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Carratalà
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, Barcelona, Spain ; CIBER de Enfermedades Respiratorias (CIBERes), ISCIII, Madrid, Spain ; Epidemiology of Bacterial Infections Group, IDIBELL, Barcelona, Spain ; Department of Pathology and Experimental Therapeutics, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Liñares
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, Barcelona, Spain ; CIBER de Enfermedades Respiratorias (CIBERes), ISCIII, Madrid, Spain ; Epidemiology of Bacterial Infections Group, IDIBELL, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ardanuy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D005838:Genotype; D006192:Haemophilus Infections / Q000188:drug therapy / Q000453:epidemiology*; D006193:Haemophilus influenzae / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000453:epidemiology*; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins