title: Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum beta-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina.
abstract: Klebsiella pneumoniae M1803, isolated from a paediatric patient with chronic urinary infection, presented nine antimicrobial resistance mechanisms harboured on two conjugative megaplasmids, in addition to the chromosomally mediated SHV-1 beta-lactamase. These nine antimicrobial resistance mechanisms comprised two extended-spectrum beta-lactamases (ESBLs) (PER-2 and CTX-M-2), TEM-1-like, OXA-9-like, AAC(3)-IIa, AAC(6')-Ib, ANT(3")-Ia and resistance determinants to tetracycline and chloramphenicol. During fluoroquinolone treatment, a variant derived from M1803 (named M1826) was selected, with an overall increase of MICs, in particular of cefoxitin and carbapenems. No enzymic activity against these latter drugs was found. Mutations in the region analogous to the quinolone resistance-determining region were not found. Strain M1826 was deficient in OmpK35/36 expression, which produced the decrease in the susceptibility to cefoxitin, carbapenems and fluoroquinolones. The blaCTX-M-2 gene was located in an unusual class 1 integron, which includes Orf513, as occurred in the recently described In35. In addition, Tn3 and Tn1331 were detected in both K. pneumoniae isolates. This is the first report of in vivo selection of an OmpK35/36 deficiency in a K. pneumoniae strain that produced a novel combination of two ESBLs (CTX-M-2 and PER-2) during fluoroquinolone treatment in a paediatric patient with chronic urinary infection.
authors.affiliation: Servicio Antimicrobianos, Dpto. Bacteriología, INEI-ANLIS Dr Carlos G. Malbrán, Av. Velez Sársfield 563 (1281), Buenos Aires, Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Melano
authors.forename: Alejandra
authors.initials: A
authors.lastname: Corso
authors.forename: Alejandro
authors.initials: A
authors.lastname: Petroni
authors.forename: Daniela
authors.initials: D
authors.lastname: Centrón
authors.forename: Betina
authors.initials: B
authors.lastname: Orman
authors.forename: Adriana
authors.initials: A
authors.lastname: Pereyra
authors.forename: Noemí
authors.initials: N
authors.lastname: Moreno
authors.forename: Marcelo
authors.initials: M
authors.lastname: Galas
mesh_terms: D001118:Argentina; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D003227:Conjugation, Genetic; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007223:Infant; D007525:Isoelectric Focusing; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D008297:Male; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D001618:beta-Lactamases