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Journal of Antimicrobial Chemotherapy (2003) 52, 36-42
© 2003 The British Society for Antimicrobial Chemotherapy

Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum ß-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina

Roberto Melano1, Alejandra Corso1, Alejandro Petroni1, Daniela Centrón2, Betina Orman2, Adriana Pereyra3, Noemí Moreno3 and Marcelo Galas1,*

1 Servicio Antimicrobianos, Dpto. Bacteriología, INEI-ANLIS ‘Dr Carlos G. Malbrán’, Av. Velez Sársfield 563 (1281), Buenos Aires; 2 Dpto. Microbiología, Facultad de Medicina, Universidad Nacional de Buenos Aires, Paraguay 2155, P. 12 (1120), Buenos Aires; 3 Servicio de Bacteriología, Hospital ‘Gobernador Centeno’, Calle 17 y 108, General Pico, Provincia de La Pampa, Argentina

Received 6 December 2002; returned 20 January 2003; revised 2 April 2003; accepted 7 April 2003

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 ß-lactamase. These nine antimicrobial resistance mechanisms comprised two extended-spectrum ß-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.

Keywords: CTX-M-2, PER-2, In35, Tn3, Tn1331

* Corresponding author. Tel/Fax: +54-11-43032812; E-mail: mgalas{at}anlis.gov.ar


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