title: Molecular epidemiology and resistance mechanisms involved in reduced susceptibility to amoxicillin/clavulanic acid in Klebsiella pneumoniae isolates from a chronic care centre.
abstract: The aim of this work was to investigate the molecular epidemiology and mechanisms responsible for reduced susceptibility to amoxicillin/clavulanic acid (AMC) amongst cefazolin-susceptible Klebsiella pneumoniae isolates from patients admitted to a chronic care institution. In total, 51 (29.8%) of 171 K. pneumoniae isolates recovered between 2006 and 2008 were non-susceptible to AMC, of which 45 were susceptible to cefazolin. Nucleotide sequencing analysis revealed that 19 produced IRT-11 and the remaining 26 were OXA-1-producers. All of the OXA-1-producing isolates harboured the aac(6')-Ib-cr-bla(OXA-1) cassette array, which in 23 isolates was located together with catB3 and arr3 within a class 1 integron and associated with qnrS2 (in 3 cases the integron lacked the qacEΔ1 and sul1 or sul3 genes). Genotyping analysis performed by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) identified three different patterns amongst IRT-11-producing isolates (E1 to E3), with E1 being the most prevalent (63.2%), whilst the OXA-1-producing isolates were assigned to patterns E3 and E3a (isolates carrying typical class 1 integrons), E4 (isolates carrying defective integrons) and E5 (isolates without integrons). Genes encoding IRT-11 and OXA-1 were transferred by conjugation, and aac(6')-Ib-cr and qnrS2 were systematically co-transferred with bla(OXA-1). These results demonstrate that the high prevalence of decreased susceptibility to AMC amongst K. pneumoniae isolates from a chronic care hospital was mainly due to the simultaneous spread of two different clones, one of which comprised isolates producing IRT-11 and the other one comprised isolates that had acquired either the bla(OXA-1) gene located in a class 1 integron and linked to qnrS2 or the bla(IRT-11) gene.
authors.affiliation: Servei Anàlisis Clíniques, Hospital de Tortosa Verge de la Cinta, C/Esplanetes s/n 43500 Tortosa, Spain. marolgap@terra.es
authors.forename: Mar Olga
authors.initials: MO
authors.lastname: Pérez-Moreno
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Centelles-Serrano
authors.forename: Maria
authors.initials: M
authors.lastname: Cortell-Ortolá
authors.forename: Isabel
authors.initials: I
authors.lastname: Fort-Gallifa
authors.forename: Joaquim
authors.initials: J
authors.lastname: Ruiz
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Llovet-Lombarte
authors.forename: Ester
authors.initials: E
authors.lastname: Picó-Plana
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Jardí-Baiges
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D003227:Conjugation, Genetic; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D023061:Gene Order; D005798:Genes, Bacterial; D005838:Genotype; D006268:Health Facilities; D006801:Humans; D032023:Integrons; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008134:Long-Term Care; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D058889:Molecular Typing; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D019980:Amoxicillin-Potassium Clavulanate Combination