title: Molecular mechanisms associated with nosocomial carbapenem-resistant Acinetobacter baumannii in Mexico.
abstract: OBJECTIVE
  Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico.
  
  
  METHODS
  A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis.
  
  
  RESULTS
  Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted.
  
  
  CONCLUSIONS
  Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico.
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México. Electronic address: alcantar@unam.mx.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Alcántar-Curiel
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México; Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D.F., México.
authors.forename: Luis Francisco
authors.initials: LF
authors.lastname: García-Torres
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México; Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D.F., México.
authors.forename: María Inés
authors.initials: MI
authors.lastname: González-Chávez
authors.affiliation: Hospital Civil de Guadalajara FAA, Instituto de Patología Infecciosa CUCS, UDG, Jalisco, México.
authors.forename: Rayo
authors.initials: R
authors.lastname: Morfín-Otero
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Catalina
authors.initials: C
authors.lastname: Gayosso-Vázquez
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: Ma Dolores
authors.initials: MD
authors.lastname: Jarillo-Quijada
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Fernández-Vázquez
authors.affiliation: Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D.F., México.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giono-Cerezo
authors.affiliation: Hospital Civil de Guadalajara FAA, Instituto de Patología Infecciosa CUCS, UDG, Jalisco, México.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rodríguez-Noriega
authors.affiliation: Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Santos-Preciado
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology*; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D006761:Hospitals; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D015378:Imipenem / Q000494:pharmacology; D000077731:Meropenem; D008800:Mexico; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D006835:Hydrazones; D013845:Thienamycins; C070053:carbonyl 3-chlorophenylhydrazone; D015378:Imipenem; D001618:beta-Lactamases; C063912:carbapenemase; D000077731:Meropenem
keywords: Acinetobacter baumannii; Carbapenem; Nosocomial infections; OXA-72; Resistance