Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 58, Issue 12, Pages 7358-7366Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.03930-14
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Funding
- Janssen Research Development
- American Proficiency Institute
- Anacor
- Astellas
- AstraZeneca
- Bayer
- Cempra
- Cerexa
- Cosmo Technologies
- Contrafect
- Cubist
- Daiichi
- Dipexium
- Enanta
- Furiex
- GlaxoSmithKline
- Johnson Johnson
- LegoChem Biosciences Inc.
- Meiji Seika Kaisha
- Merck
- Nabriva
- Novartis
- Pfizer (Wyeth)
- PPD Therapeutics
- Rempex
- Melinta (Rib-X) Pharmaceuticals
- Seachaid
- Shionogi
- Medicines Co.
- Theravance
- ThermoFisher
- Vertex Pharmaceuticals
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We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB; n = 411) and Enterobacteriaceae (n = 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 mu g/ml) isolates were screened for carbapenemases. New beta-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of beta-lactam intrinsic resistance mechanisms was determined for carbapenemase-negative Enterobacteriaceae. ACB and Enterobacteriaceae displayed 58.9 and 0.9% doripenem resistance, respectively. bla(OXA-23), bla(OXA-58), and bla(OXA-24/OXA-40) were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 countries). Ten Turkish isolates carried bla(GES-11) or bla(GES-22). GES-22 (G243A and M169L mutations in GES-1) had an extended-spectrum beta-lactamase profile. A total of 33 clusters of >= 2 ACB isolates were observed, and 227 isolates belonged to sequence type 2/international clone II. Other international clones were limited to Turkey and Israel. Doripenem-resistant Enterobacteriaceae increased significantly (0.7 to 1.6%), and 15 bla(KPC-2)-and 22 bla(KPC-3)-carrying isolates, mostly belonging to clonal complexes 11 and 258, were observed. Enterobacteriaceae isolates producing OXA-48 (n = 16; in Turkey and Italy), VIM-1 (n = 10; in Greece, Poland, and Spain), VIM-26 (n = 1; in Greece), and IMP-19, VIM-4, and the novel VIM-35 (n = 1 each from Poland) were detected. VIM-35 had one substitution compared to VIM-1 (A235T) and a similar susceptibility profile. One or more resistance mechanisms were identified in 4/6 carbapenemase-negative Enterobacteriaceae. This broad evaluation confirms results from country-specific surveys and shows a highly diverse population of carbapenemase-producing ACB and Enterobacteriaceae in Europe and Mediterranean countries.
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