title: Antibiotic coresistance in extended-spectrum-beta-lactamase-producing Enterobacteriaceae and in vitro activity of tigecycline.
abstract: The spread of extended-spectrum-beta-lactamase (ESBL)-producing organisms, particularly those harboring the CTX-M-type enzymes, both in the hospital and in the community, is difficult to discontinue due to the successful mobilization and evolution of the genetic elements harboring ESBL genes and coresistance rates in these isolates. The activities of tigecycline against 285 non-clonally related isolates (172 from Escherichia coli, 84 from Klebsiella spp., 20 from Enterobacter spp., 5 from Salmonella spp., and 4 from Citrobacter spp.) expressing well-characterized ESBLs and recovered in our hospital and its community area of influence were comparatively assessed (CLSI microdilution). Susceptibility rates for meropenem, imipenem, tigecycline, amikacin, and piperacillin-tazobactam were 100%, 100%, 97.5%, 93.3%, and 93%, respectively. Tigecycline (mode MIC, 0.5 microg/ml; MIC(90), 1 microg/ml) was 4- to 256-fold more active than doxycycline and minocycline (mode MIC range, 2 to 128 microg/ml). CTX-Ms were the most frequent ESBLs (61.4%), 65.8% in community and 58.6% in nosocomial isolates. CTX-M-9 (22%), CTX-M-14 (15.8%), and CTX-M-10 (14%) were the most represented derivatives. SHV and TEM variants constituted 22.8% and 15.8% of the ESBLs, respectively. Overall coresistance rates were as follows: gentamicin, 27.4%; tobramycin, 27.4%; amikacin, 6.7%; and chloramphenicol, 29.1%. Sulfonamide (61.7%), trimethoprim (52.3%), streptomycin (50.5%), and ciprofloxacin (37.2%) resistance levels were significantly (P < 0.001) associated with CTX-M-9 producers. No tigecycline resistance was observed, although seven Klebsiella pneumoniae isolates exhibited intermediate MICs (4 mug/ml). Tigecycline, lacking cross-resistance with other compounds, could represent an opportunity to reduce the intensity of selection for ESBL-producing organisms derived from the use of other antimicrobial agents. However, this in vitro promise requires support from clinical studies.
authors.affiliation: Servicio de Microbiología, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Morosini
authors.forename: María
authors.initials: M
authors.lastname: García-Castillo
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Coque
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Valverde
authors.forename: Angela
authors.initials: A
authors.lastname: Novais
authors.forename: Elena
authors.initials: E
authors.lastname: Loza
authors.forename: Fernando
authors.initials: F
authors.lastname: Baquero
authors.forename: Rafael
authors.initials: R
authors.lastname: Cantón
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017714:Community-Acquired Infections; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology; D006785:Hospitals, University; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078304:Tigecycline; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000078304:Tigecycline; D001618:beta-Lactamases; D008911:Minocycline