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Antimicrobial Agents and Chemotherapy, September 2006, p. 3222-3224, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00284-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Emergence of PER-2 and VEB-1a in Acinetobacter baumannii Strains in the Americas

Top Letter References

 
Antimicrobial treatment of Acinetobacter infections may be limited because of the emergence of extended-spectrum ß-lactamase (ESBL)- and carbapenemase-producing multiresistant strains (7, 13). Non-TEM-, non-SHV-derived ESBLs (such as PER and VEB) have been documented in Acinetobacter isolates from Europe and Asia (7) but not yet from the Americas.

Recently, an increasing trend has been documented in carbapenem and extended-spectrum cephalosporin resistance in Acinetobacter isolates in Buenos Aires. Indeed, data from the Whonet-Argentina Network showed that, in 2004, more than 80% of Acinetobacter isolates were resistant to extended-spectrum cephalosporins. In addition, imipenem resistance increased from 5% to 54%, in the period from 2000 to 2004 (M. Galas, unpublished results). National ESBL surveillance is performed by Whonet-Argentina Network participants using a modification of the CLSI antibiogram (8), consisting of a synergy test with ceftazidime or cefepime and amoxicillin-clavulanic acid (distance between disks, 20 mm, center to center).

FAV-1 and M5179 were the first putative ESBL-producing Acinetobacter baumannii strains isolated at two hospitals in Buenos Aires in 2000 and 2003, respectively. FAV-1 was a colonizer from the urine of a patient hospitalized for lung transplantation. M5179 was from the peritoneal fluid of a patient with hemolytic-uremic syndrome. Strains were confirmed to be A. baumannii by using the API 20NE system (bioMérieux, Marcy l'Etoile, France) combined with their ability to grow at 44°C.

MICs (micrograms per milliliter) for FAV-1 and M5179 determined by agar dilution (10) were, respectively, as follows: ticarcillin, 1,024 and 1,024; piperacillin, 512 and 256; piperacillin-tazobactam, 512 and 0.5; ampicillin-sulbactam, 8 and 8; cefotaxime, 64 and 64; cefotaxime-clavulanate, 64 and 8; ceftazidime, 64 and 512; ceftazidime-clavulanate, 16 and 2; cefepime, 64 and 64; cefepime-clavulanate, 16 and 4; aztreonam, 512 and 512; imipenem, 8 and 0.5; meropenem, 8 and 0.5; amikacin, 128 and 32; gentamicin, 2 and 32; trimethoprim-sulfamethoxazole, 128 and 8; ciprofloxacin, 32 and 0.12; rifampin, 2 and >32; minocycline, 0.5 and <0.25. EDTA (0.4 mM) did not affect carbapenem MICs.

Attempts to transfer the ceftazidime (FAV-1 and M5179) or imipenem (FAV-1) resistance marker by conjugation or electroporation to Escherichia coli ER1793 (6) were unsuccessful.

Isoelectric focusing analysis (6) revealed ESBL bands at pIs of 5.4 (FAV-1) and 7.4 (M5179) and narrow-spectrum ß-lactamase bands at pIs of 6.9, 9.4 (FAV-1), and 5.4 (M5179). A band at a pI of 9.4 was inhibited by oxacillin (1 mM) (probable AmpC-like enzyme). A band at a pI of 6.9 showed weak activity against imipenem and was not inhibited by oxacillin, clavulanate (1 mM), or EDTA (30 mM).

In the PCR screening for ESBL genes (Table 1), amplifications of bla_PER (FAV-1) or bla_TEM and bla_VEB (M5179) were positive. DNA sequencing identified the genes as bla_PER-2, bla_TEM-1, and bla_VEB-1a (11) (the latter unequivocally identified by full-length amplification and sequencing). PCR mapping with class 1 integron-bla_VEB primer combinations (5'-CS-VEB-R, IntI1-F-VEB-R, VEB-F-3'-CS, and VEB-F-sulI-R) under either conventional or long amplification (Elongase Amplification System, Invitrogen, California) conditions yielded negative results. A PCR assay with primers 5'-CS and 3'-CS resulted in a unique amplicon of 1,395 bp that carried arr-2 (first report in Argentina) and aacA4 cassettes (4). PCRs with primers targeting intI2 and intI3 or with primer combinations 3'-CS-VEB-R, 3'-CS-VEB-Rc, sulI-R-VEB-R, and sulI-R-VEB-Rc, to target antisense insertion of bla_VEB-1a (1), also failed to generate amplicons. These data suggested an unusual localization of the bla_VEB-1a gene in M5179.

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TABLE 1. Primers used in this study

The PCR characterization of the carbapenemase-encoding genes in FAV-1 (Table 1) yielded positive amplifications for bla_OXA subgroup 3 and bla_OXA-58. The identities of bla_OXA-51 and bla_OXA-58 were determined by amplification and sequencing of complete genes and flanking regions as described previously (2) (GenBank accession numbers DQ385606 and DQ385607, respectively). The region upstream of bla_OXA-51 showed 79% identity with a fragment of the Acinetobacter sp. strain ADP1 genome (positions 2,028,863 to 2,029,156 in the sequence with GenBank accession number CR543861), supporting its previously proposed chromosomal location (3). The genetic environment of bla_OXA-58 was the same as that in an A. baumannii isolate from France, i.e., bracketed by two ISAba3 elements in opposite orientations (10).

This is the first report of VEB- and PER-producing Acinetobacter strains in the Americas and also the first documentation of a VEB-type enzyme on this continent. Since 2003, a nationwide surveillance effort to address the degree of dissemination of ESBLs among Acinetobacter strains in Argentina has revealed the occurrence of 21 ESBL-producing isolates, PER-2 (n = 11) and VEB (n = 10), in four provinces. Therefore, the emergence of both VEB and PER-2 in Acinetobacter strains in Argentina constitutes a public health concern.

 
Fernando Pasterán and Melina Rapoport contributed equally to this work.

Top Letter References

 

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5. Levesque, C., L. Piche, C. Larose, and P. H. Roy. 1995. PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob. Agents Chemother. 39:185-191.[Abstract]
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7. Naas, T., P. Bogaerts, C. Bauraing, Y. Degheldre, Y. Glupczynski, and P. Nordmann. 2006. Emergence of PER and VEB extended-spectrum ß-lactamases in Acinetobacter baumannii in Belgium. J. Antimicrob. Chemother. 0:dkl178v1. [Epub ahead of print.]
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9. Pasteran, F., D. Faccone, A. Petroni, M. Rapoport, M. Galas, M. Vazquez, and A. Procopio. 2005. Novel variant (bla_VIM-11) of the metallo-ß-lactamase bla_VIM family in a GES-1 extended-spectrum-ß-lactamase-producing Pseudomonas aeruginosa clinical isolate in Argentina. Antimicrob. Agents Chemother. 49:474-475.[Free Full Text]
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						Fernando Pasterán Melina Rapoport Alejandro Petroni Diego Faccone Alejandra Corso Marcelo Galas* Servicio Antimicrobianos Departamento Bacteriología Instituto Nacional de Enfermedades Infecciosas-ANLIS "Carlos G. Malbrán" Ciudad Autónoma de Buenos Aires, Argentina,1 Miryam Vázquez Adriana Procopio Sección Microbiología Hospital de Niños "Ricardo Gutiérrez" Gobierno de Buenos Aires Ciudad Autónoma de Buenos Aires, Argentina,2 Marta Tokumoto Viviana Cagnoni Instituto de Cardiología y Cirugía Cardiovascular "Fundación Favaloro" Ciudad Autónoma de Buenos Aires, Argentina,3
						* Phone and fax: 54 11 4 303 2812, E-mail: mgalas{at}anlis.gov.ar

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Antimicrobial Agents and Chemotherapy, September 2006, p. 3222-3224, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00284-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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