1. Genomics And Susceptibility Profiles Of Extensively Drug-resistant Pseudomonas Aeruginosa Isolates From Spain
- Author
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Ester del Barrio-Tofiño, Luisa Sorlí, José Antonio Martínez, Concepción Segura, Fe Tubau, Antonio Oliver, Luis Martínez-Martínez, Natividad Benito, Alba Rivera, Gabriel Cabot, Elena Resino-Foz, Juan Pablo Horcajada, Raquel Durá-Navarro, Laura Zamorano, María Milagro Montero, Cristina Labayru-Echverria, Silvia Gómez-Zorrilla, Marta Fernández-Martínez, Ignacio Ayestarán, Esther Viedma, Carlos Dueñas, Izaskun Alejo-Cancho, Carla López-Causapé, Claudia González-Rico, Nuria Tormo, [del Barrio-Tofino, Ester] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Dept Microbiol, Intens Care Unit, Palma De Mallorca, Spain, [Lopez-Causape, Carla] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Dept Microbiol, Intens Care Unit, Palma De Mallorca, Spain, [Cabot, Gabriel] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Dept Microbiol, Intens Care Unit, Palma De Mallorca, Spain, [Ayestaran, Ignacio] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Dept Microbiol, Intens Care Unit, Palma De Mallorca, Spain, [Zamorano, Laura] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Dept Microbiol, Intens Care Unit, Palma De Mallorca, Spain, [Oliver, Antonio] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Dept Microbiol, Intens Care Unit, Palma De Mallorca, Spain, [del Barrio-Tofino, Ester] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Unidad Invest, Palma De Mallorca, Spain, [Lopez-Causape, Carla] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Unidad Invest, Palma De Mallorca, Spain, [Cabot, Gabriel] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Unidad Invest, Palma De Mallorca, Spain, [Ayestaran, Ignacio] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Unidad Invest, Palma De Mallorca, Spain, [Zamorano, Laura] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Unidad Invest, Palma De Mallorca, Spain, [Oliver, Antonio] Hosp Univ Son Espases, Inst Invest Illes Balears IdISBa, Unidad Invest, Palma De Mallorca, Spain, [Rivera, Alba] Hosp Santa Creu & Sant Pau, Dept Microbiol & Infect Dis, Barcelona, Spain, [Benito, Natividad] Hosp Santa Creu & Sant Pau, Dept Microbiol & Infect Dis, Barcelona, Spain, [Segura, Concepcion] Hosp del Mar, Lab Referencia Catalunya, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Milagro Montero, Maria] Hosp del Mar, Lab Referencia Catalunya, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Sorli, Luisa] Hosp del Mar, Lab Referencia Catalunya, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Pablo Horcajada, Juan] Hosp del Mar, Lab Referencia Catalunya, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Segura, Concepcion] Hosp del Mar, Dept Infect Dis, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Milagro Montero, Maria] Hosp del Mar, Dept Infect Dis, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Sorli, Luisa] Hosp del Mar, Dept Infect Dis, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Pablo Horcajada, Juan] Hosp del Mar, Dept Infect Dis, Infect Pathol & Antimicrobial Res Grp IPAR, Inst Hosp del Mar Invest Med IMIM, Barcelona, Spain, [Tubau, Fe] Hosp Univ Bellvitge, Dept Microbiol & Infect Dis, Barcelona, Spain, [Gomez-Zorrilla, Silvia] Hosp Univ Bellvitge, Dept Microbiol & Infect Dis, Barcelona, Spain, [Tormo, Nuria] Consorcio Hosp Gen Univ Valencia, Dept Microbiol & Infect Dis, Valencia, Spain, [Dura-Navarro, Raquel] Consorcio Hosp Gen Univ Valencia, Dept Microbiol & Infect Dis, Valencia, Spain, [Viedma, Esther] Hosp Univ 12 Octubre, Dept Microbiol & Infect Dis, Madrid, Spain, [Resino-Foz, Elena] Hosp Univ 12 Octubre, Dept Microbiol & Infect Dis, Madrid, Spain, [Fernandez-Martinez, Marta] Hosp Univ Marques de Valdecilla, Inst Invest Valdecilla IDIVAL, Dept Microbiol & Infect Dis, Santander, Spain, [Gonzalez-Rico, Claudia] Hosp Univ Marques de Valdecilla, Inst Invest Valdecilla IDIVAL, Dept Microbiol & Infect Dis, Santander, Spain, [Alejo-Cancho, Izaskun] Hosp Univ Clin, Dept Microbiol & Infect Dis, Barcelona, Spain, [Antonio Martinez, Jose] Hosp Univ Clin, Dept Microbiol & Infect Dis, Barcelona, Spain, [Labayru-Echverria, Cristina] Hosp Univ Burgos, Dept Microbiol & Infect Dis, Burgos, Spain, [Duenas, Carlos] Hosp Univ Burgos, Dept Microbiol & Infect Dis, Burgos, Spain, [Martinez-Martinez, Luis] Univ Cordoba, Hosp Univ Reina Sofia, Dept Microbiol, Unit Microbiol, Cordoba, Spain, [Martinez-Martinez, Luis] Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain, Plan Nacional de I+D+i, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases, and European Development Regional Fund (ERDF)
- Subjects
0301 basic medicine ,Imipenem ,Ceftazidime ,Penicillanic Acid ,Aztreonam ,Drug resistance ,medicine.disease_cause ,Antimicrobial resistance ,chemistry.chemical_compound ,polycyclic compounds ,Pharmacology (medical) ,Aminoglycoside resistance ,Molecular Epidemiology ,extensively drug resistant ,Beta-lactam resistance ,Ceftolozane-tazobactam ,Broth microdilution ,3. Good health ,Anti-Bacterial Agents ,Infectious Diseases ,high-risk clones ,Amikacin ,whole-genome sequencing ,Molecular epidemiology ,Pseudomonas aeruginosa ,Erratum ,Convergent evolution ,Mutations ,medicine.drug ,Fluoroquinolones ,Field gel-electrophoresis ,Tazobactam ,Carbapenem resistance ,Cxa-101 fr264205 ,Epidemiologia molecular ,030106 microbiology ,Microbial Sensitivity Tests ,Biology ,beta-Lactam Resistance ,beta-Lactamases ,Microbiology ,03 medical and health sciences ,Polymyxin resistance ,Bacterial Proteins ,Pseudomonas ,Drug Resistance, Bacterial ,medicine ,Humans ,Pseudomonas Infections ,Polymyxins ,Pharmacology ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Cephalosporins ,Aminoglycosides ,chemistry ,Spain - Abstract
This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis–multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% ( n = 101) of the XDR isolates, distantly followed by ST244 ( n = 16), ST253 ( n = 12), ST235 ( n = 8), and ST111 ( n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital ( n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the β-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
- Published
- 2017