[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Genetic Markers of Widespread Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa High-Risk Clones

Gabriel Cabot 1, Alain A. Ocampo-Sosa 2, M.Angeles Dom?nguez 3, Juan F. Gago 1, Carlos Juan 1, Fe Tubau 3, Cristina Rodr?guez 2, Bartolom? Moy? 1, Carmen Pe?a 3, Luis Mart?nez-Mart?nez 2 and Antonio Oliver 1,* Spanish Network for Research in Infectious Diseases (REPI)

Author Affiliations: <SUP>1</SUP>Servicio de Microbiolog?a y Unidad de Invesitgaci?n, Hospital Universitario Son Espases, Palma de Mallorca, Spain <SUP>2</SUP>Servicio de Microbiolog?a, Hospital Universitario Marqu?s de Valdecilla-IFIMAV, Santander, Spain <SUP>3</SUP>Servicios de Microbiolog?a y Enfermedades Infecciosas, Hospital Universitario de Bellvitge, Barcelona, Spain


Recent reports have revealed the existence of widespread extensively drug-resistant (XDR) P. aeruginosa high-risk clones in health care settings, but there is still scarce information on their specific chromosomal (mutational) and acquired resistance mechanisms. Up to 20 (10.5%) of 190 bloodstream isolates collected from 10 Spanish hospitals met the XDR criteria. A representative number (15 per group) of isolates classified as multidrug-resistant (MDR) (22.6%), resistant to 1-2 classes (modR) (23.7%), or susceptible to all antibiotics (multiS) (43.2%) were investigated in parallel. MLST analysis revealed that all XDR isolates belonged to ST175 (n=19) or ST111 (n=1), both recognized as international high-risk clones. Clonal diversity was higher among the 15 MDR isolates (4 ST175, 2 ST111, and 8 additional STs) and especially among the 15 modR (13 different STs) and multiS (14 STs) isolates. The XDR/MDR pattern in ST111 isolates correlated with the production of VIM-2, but none of the ST175 isolates produced acquired β-lactamases. In contrast, the analysis of resistance markers in 12 representative isolates (from 7 hospitals) of ST175 revealed that the XDR pattern was driven by the combination of AmpC hyperproduction, OprD inactivation (Q142X), 3 mutations conferring high-level fluoroquinolone resistance (GyrA T83I and D87N and ParC S87W), a G195E mutation in MexZ (involved in MexXY-OprM overexpression), and the production of a class 1 integron harboring the aadB gene (gentamicin and tobramycin resistance). Of particular interest, in nearly all the ST175 isolates, AmpC hyperproduction was driven by a novel AmpR-activating mutation (G154R), as demonstrated by complementation studies using an ampR mutant of PAO1. This work first describes the specific resistance markers of widespread P. aeruginosa XDR high-risk clones producing invasive infections.


*Corresponding author: Antonio Oliver, Servicio de Microbiolog?a, Hospital Son Espases, Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain, Phone: 34 871 20 62 62, e-mail: antonio.oliver@ssib.es

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