Genetic Markers of Widespread Extensively Drug-Resistant Pseudomonas aeruginosa High-Risk Clones
被引:189
作者:
Cabot, Gabriel
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Hosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Hosp Univ Son Espases, Unidad Invest, Palma de Mallorca, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Cabot, Gabriel
[1
,2
]
Ocampo-Sosa, Alain A.
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Hosp Univ Marques de Valdecilla IFIMAV, Microbiol Serv, Santander, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Ocampo-Sosa, Alain A.
[3
]
Angeles Dominguez, M.
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Hosp Univ Bellvitge, Serv Microbiol & Enfermedades Infecciosas, Barcelona, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Angeles Dominguez, M.
[4
]
Gago, Juan F.
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Hosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Hosp Univ Son Espases, Unidad Invest, Palma de Mallorca, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Gago, Juan F.
[1
,2
]
Juan, Carlos
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Hosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Hosp Univ Son Espases, Unidad Invest, Palma de Mallorca, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Juan, Carlos
[1
,2
]
Tubau, Fe
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Hosp Univ Bellvitge, Serv Microbiol & Enfermedades Infecciosas, Barcelona, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Tubau, Fe
[4
]
Rodriguez, Cristina
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Hosp Univ Marques de Valdecilla IFIMAV, Microbiol Serv, Santander, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Rodriguez, Cristina
[3
]
Moya, Bartolome
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Hosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Hosp Univ Son Espases, Unidad Invest, Palma de Mallorca, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Moya, Bartolome
[1
,2
]
Pena, Carmen
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Hosp Univ Bellvitge, Serv Microbiol & Enfermedades Infecciosas, Barcelona, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Pena, Carmen
[4
]
Martinez-Martinez, Luis
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Hosp Univ Marques de Valdecilla IFIMAV, Microbiol Serv, Santander, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Martinez-Martinez, Luis
[3
]
Olivera, Antonio
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Hosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Hosp Univ Son Espases, Unidad Invest, Palma de Mallorca, SpainHosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
Olivera, Antonio
[1
,2
]
机构:
[1] Hosp Univ Son Espases, Microbiol Serv, Palma de Mallorca, Spain
[2] Hosp Univ Son Espases, Unidad Invest, Palma de Mallorca, 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 to 2 classes (moderately resistant [modR]) (23.7%), or susceptible to all antibiotics (multiS) (43.2%) were investigated in parallel. Multilocus sequence typing (MLST) analysis revealed that all XDR isolates belonged to sequence type 175 (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 high 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 beta-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 is the first to describe the specific resistance markers of widespread P. aeruginosa XDR high-risk clones producing invasive infections.