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Antimicrobial Agents and Chemotherapy, September 2006, p. 3220-3221, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00473-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Dissemination in Portugal of CTX-M-15-, OXA-1-, and TEM-1-Producing Enterobacteriaceae Strains Containing the aac(6')-Ib-cr Gene, Which Encodes an Aminoglycoside- and Fluoroquinolone-Modifying Enzyme

	LETTER

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We report the dissemination of bla_CTX-M-15 associated with strains and plasmids harboring bla_OXA-1, bla_TEM-1, and the recently described aac(6')-Ib-cr gene, which encodes an aminoglycoside- and fluoroquinolone-modifying enzyme (12) in different Portuguese regions.

During a surveillance study of ESBL-producing isolates in two hospitals and one ambulatory laboratory in three different Portuguese cities (January 2003 to October 2004), we identified 17 E. coli and 2 Klebsiella pneumoniae isolates producing CTX-M-15 (Table 1). Susceptibility testing and characterization of ß-lactamases were performed by standard methods (2, 7). The presence of resistance genes such as aac(6')-Ib-cr, qnrA, or qnrB or sequences linked to CTX-M-genetic environments such as ISEcp1, IS903, class 1 integrons, or CR1 (also named open reading frame 513 [ORF513]) was investigated by PCR and sequencing (5, 7, 8, 12, 13). PCR experiments based on published sequences (GenBank accession no. AY458016 and AY259086) were performed to search the vicinity of particular genes. Clonal relatedness was established by pulsed-field gel electrophoresis (PFGE) and identification of E. coli phylogenetic groups by a multiplex PCR assay (7). Conjugation experiments were carried out as described previously (7). Plasmid analysis included estimation of plasmid number and size and comparison of EcoRI-digested DNA patterns (1).

Most strains simultaneously produced CTX-M-15, OXA-1, and TEM-1. The gene bla_CTX-M-15 was located 49 nucleotides downstream of ISEcp1 in plasmids of 85 (n = 16), 100 (n = 1), or 120 (n = 2) kb. The presence of IS903 was detected only in K. pneumoniae isolates. When transferred by conjugation (achieved in one K. pneumoniae isolate and four E. coli isolates), bla_CTX-M-15 was accompanied by bla_OXA-1, bla_TEM-1, and genes coding for decreased susceptibility to tetracycline, kanamycin, gentamicin, tobramycin, amikacin, and ciprofloxacin.

We identified the gene cassette array aac(6')-Ib-cr-bla_OXA-1 in all CTX-M-15- and OXA-1-producing isolates, despite the absence of detectable class 1 integrons, CR1, qnrA, or qnrB, as also happens in pC15-1a, the epidemic plasmid coding for CTX-M-15 described in Canada (3). It is of note that the recently described aac(6')-Ib-cr gene, which reduces the activity of both aminoglycosides (kanamycin, tobramycin, and amikacin) and fluoroquinolones (ciprofloxacin and norfloxacin), appears to be associated with bla_OXA-1 either in In37, a class 1 integron bearing CR1 and carrying qnrA, or in the multiresistance region of pC15-1a, even though this has not been recognized to date (3, 12, 13).

Our results indicate that current dissemination of bla_CTX-M-15 in Portugal is linked to an epidemic E. coli strain of phylogroup B2 and/or plasmids also containing bla_OXA-1, bla_TEM-1, and aac(6')-Ib-cr resistance genes, both sharing similar features with others reported in different continents (3, 6, 11, 14). These findings are of concern since different selective pressures might contribute to the persistence and broad dissemination of these multiresistant genetic elements. They also suggest that the relationships among epidemic genetic elements bearing bla_CTX-M-15 of distinct geographical areas require further investigation.

	ACKNOWLEDGMENTS

 
Elisabete Machado was supported by a fellowship from Fundação para a Ciência e a Tecnologia de Portugal (SFRH/BD/11304/2002).

Contributing members of the Portuguese Resistance Study Group are Helena Ramos, Hospital Geral de Santo António (NH), Porto, Portugal; Graça Ribeiro and Clementina Vital, Hospitais Universitários de Coimbra (CH), Coimbra, Portugal; and Sónia Magalhães, LabFafe (NAL), Fafe, Portugal.

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