title: In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enterococci.
abstract: We compared ceftriaxone and piperacillin-tazobactam at doses ranging from 0.1 to 2 times the human equivalent daily dose (HEDD), to determine their impact on gastrointestinal colonization by ampicillin- and vancomycin-resistant Enterococcus faecium C68 in a mouse model. Ceftriaxone failed to promote colonization at doses up to 0.25 times the HEDD, whereas piperacillin-tazobactam promoted colonization at doses up to 0.5 times the HEDD. Ceftriaxone promoted colonization at doses at least 0.5 times the HEDD, whereas piperacillin-tazobactam inhibited colonization at doses at least 0.75 times the HEDD. Both piperacillin-tazobactam and ceftriaxone inhibited colonization by an enterococcal strain devoid of low-affinity penicillin-binding protein-5 (significantly increasing its susceptibility to these agents), at doses that promoted colonization by E. faecium C68. These results support a model in which the impact that different beta -lactam agents have on colonization by VRE is related to the level of the beta -lactam agent's intrinsic antienterococcal activity against the colonizing strain.
authors.affiliation: Medical and Research Services, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio 44106, USA. louis.rice@med.va.gov
authors.forename: Louis B
authors.initials: LB
authors.lastname: Rice
authors.forename: Viera
authors.initials: V
authors.lastname: Lakticová
authors.forename: Marion S
authors.initials: MS
authors.lastname: Helfand
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hutton-Thomas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002353:Carrier State / Q000517:prevention & control*; D002443:Ceftriaxone / Q000008:administration & dosage / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects*; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control; D051379:Mice; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D010878:Piperacillin / Q000008:administration & dosage / Q000494:pharmacology*; D000077725:Piperacillin, Tazobactam Drug Combination
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D002443:Ceftriaxone; D010397:Penicillanic Acid; D010878:Piperacillin