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Antimicrobial Agents and Chemotherapy, November 2008, p. 4205-4206, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01121-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

Carbapenem-Resistant Acinetobacter baumannii Isolates Expressing the bla_OXA-23 Gene Associated with ISAba4 in Belgium

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Carbapenems are among the drugs of choice for treating nosocomial infections due to multidrug-resistant Acinetobacter baumannii strains (4). However, their efficacy is being increasingly compromised by the spread of carbapenem-resistant isolates, mostly following acquisition of carbapenemases of class D (OXA-23, OXA-40-like, and OXA-58 oxacillinases) (1, 6, 8, 9). Outbreaks of OXA-23-producing A. baumannii isolates are increasingly being reported worldwide (7, 8). In these isolates, bla_OXA-23 is associated with an upstream-inserted insertion sequence, ISAba1, which is responsible for its mobilization and expression. In two unrelated A. baumannii isolates from France, the bla_OXA-23 gene was associated with another insertion sequence, ISAba4 (3). Here, we describe the first ISAba4-bla_OXA-23-expressing A. baumannii isolates in Belgium.

In July 2007, a 69-year-old Belgian resident was admitted to the intensive care unit (ICU) of a general hospital in Morocco with a diagnosis of pneumonia and cardiac failure. The patient was transferred to the ICU of Saint-Joseph Hospital (Gilly, Belgium), and culture of respiratory secretions grew a carbapenem-resistant and multidrug-resistant A. baumannii strain, GIL1. Despite prompt treatment with colistin, the patient died.

The A. baumannii isolate was identified with the API 32GN system (BioMérieux, Marcy-l'Etoile, France) and confirmed by detection of the intrinsic bla_oxa-51/69-like gene (10). According to MIC determination by Etest (AB Biodisk, Solna, Sweden), A. baumannii GIL1 was resistant to all β-lactams (2), including imipenem and meropenem (MIC, >32 µg/ml), sulbactam (MIC, 48 µg/ml), ciprofloxacin (MIC, >32 µg/ml) and amikacin (MIC, >256 µg/ml); borderline susceptible to tigecycline (MIC, 6 µg/ml) and rifampin (MIC 3 µg/ml); and fully susceptible to colistin only (MIC, 0.5 µg/ml).

PCR analysis followed by sequencing revealed that A. baumannii GIL1 harbored the bla_OXA-23 gene, along with the naturally and chromosomally located bla_OXA-69 gene and a novel bla_ADC allele (5), bla_ADC-39 (GenBank accession no. EU652244). bla_ADC-39 differed from the A. baumannii AYE bla_AmpC gene (GenBank accession no. CT025798) by only two nucleotide substitutions (A1022C and G1135A) leading to two amino acid changes (N351T and D379N). Isoelectric focusing confirmed the expression of OXA-23 (pI 6.3 to 6.5) and ADC-39 β-lactamase (pI >8.5) (not shown). Using a previously described PCR approach (3), ISAba1 was found inserted upstream of bla_ADC-39 gene but not upstream of the bla_OXA-23 or bla_OXA-69 gene. Instead, another insertion sequence, ISAba4, was found upstream of the bla_OXA-23 gene, with a genetic organization similar to that described for Tn2007: i.e., orf3 and mobA genes surrounding the ISAba4-bla_OXA-23-ATPase fragment inserted in orf1 (3) (Fig. 1).

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FIG. 1. Genetic organization of the three β-lactamase genes found in A. baumannii GIL1. (A) ISAba4-blaOXA-23. (B) ISAba1-blaADC-39. (C) blaOXA-69. Horizontal arrows represent open reading frames and their transcriptional orientations. Promoters brought by the insertion sequences are indicated by small vertical arrows.

The bla_OXA-23 gene was encoded on a 25-kb plasmid that could be electroporated into rifampin-resistant A. baumannii CIP7010 but was not self-transferable by conjugation. Only the bla_OXA-23 gene was transferred in the electroporants, as revealed by susceptibility testing.

Since the initial detection of this strain, six other patients of the ICU have been identified as carriers or infected with ISAba4-bla_OXA-23-expressing A. baumannii isolates. These isolates were indistinguishable by pulsed-field gel electrophoresis, suggesting clonal diffusion. Furthermore, pulsed-field gel electrophoresis analysis revealed that A. baumannii GIL1 presented identical banding patterns to one ISAba4-bla_OXA-23 A. baumannii isolate reported in France, thus illustrating its propensity to disseminate and underscoring the need for epidemic surveys geared to estimate the true prevalence of these ISAba4-OXA-23 producers. ISAba1 and ISAba4 have been suggested to be at the origin of bla_OXA-23 gene mobilization and to provide strong promoter sequences for their expression (3). Whether ISAba4 may procure a fitness advantage over ISAba1 in A. baumannii strains in terms of transposition frequency or level of expression needs to be further investigated.

 
This work was funded by a grant from the Belgian Antibiotic Policy Coordination Committee (BAPCOC), Ministry of Public Health; from the Ministère de l'Education Nationale et de la Recherche (UPRES-EA3539), Université Paris XI, France; and mostly by the European Community (6th PCRD, LSHM-CT-2005-018-705).

The ADC (Acinetobacter-derived cephalosporinase) number was kindly assigned by Miriam Barlow.

 
Published ahead of print on 2 September 2008.

Top LETTER REFERENCES

 

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						Pierre Bogaerts* Laboratoire de Bactériologie Université Catholique de Louvain Cliniques Universitaires UCL de Mont-Godinne 1, Av. Dr. Gaston Thérasse B-5530 Yvoir, Belgium Gaelle Cuzon Thierry Naas Service de Bactériologie-Virologie Hôpital de Bicêtre Assistance Publique-Hôpitaux de Paris 94275 Le Kremlin-Bicêtre, Faculté de Médecine Paris-Sud, France Caroline Bauraing Laboratoire de Bactériologie Université Catholique de Louvain Cliniques Universitaires UCL de Mont-Godinne B-5530 Yvoir, Belgium Ariane Deplano Unité de Microbiologie Hôpital Erasme, Université Libre de Bruxelles B-1070 Brussels, Belgium Bénédicte Lissoir Laboratoire de Bactériologie Hôpital Saint-Joseph B-6060 Gilly, Belgium Patrice Nordmann INSERM U914: Emerging Resistance to Antibiotics Paris, France Youri Glupczynski Laboratoire de Bactériologie Université Catholique de Louvain UCL-Mont-Godinne Yvoir, Belgium
						* Phone: 32-81-42-32-41, Fax: 32-81-42-32-46, E-mail: pierre.bogaerts{at}uclouvain.be

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Antimicrobial Agents and Chemotherapy, November 2008, p. 4205-4206, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01121-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bogaerts, P. Articles by Glupczynski, Y. Search for Related Content PubMed PubMed Citation Articles by Bogaerts, P. Articles by Glupczynski, Y.