title: Catecholamine inotrope resuscitation of antibiotic-damaged staphylococci and its blockade by specific receptor antagonists.
abstract: The increasing use of antibiotic-coated catheters, such as those containing rifampin or minocycline, has led to a decrease in catheter colonization by staphylococci but not to a decrease in the incidence of catheter-related bloodstream infection (BSI). Because catheters are used for the administration of catecholamine inotropes to maintain cardiac function, we examined whether 2 commonly employed inotropes, dopamine and norepinephrine, could affect bacterial viability after exposure to rifampin and minocycline. Rifampin inhibition and minocycline inhibition of staphylococcal growth could be reversed by exposure to dopamine or norepinephrine as a result, in part, of catecholamine-mediated increased provision of host-sequestered iron. The simultaneous addition of inotropes with an antibiotic did not affect antibiotic susceptibility. Inotrope-induced growth in bacteria previously exposed to antibiotics was blocked by the inclusion in culture media of specific catecholamine-receptor antagonists. Considered collectively, these results provide a mechanistic basis for understanding how host-related factors, such as inotrope-based therapeutics, may influence the recovery of antibiotic-stressed bacteria in clinical settings.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, University of Leicester, United Kingdom.
authors.forename: Primrose P E
authors.initials: PP
authors.lastname: Freestone
authors.forename: Richard D
authors.initials: RD
authors.lastname: Haigh
authors.forename: Mark
authors.initials: M
authors.lastname: Lyte
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects*; D008911:Minocycline / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013210:Staphylococcus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D002316:Cardiotonic Agents; D018492:Dopamine Antagonists; D006133:Growth Substances; D007501:Iron; D008911:Minocycline; D012293:Rifampin; D004298:Dopamine; D009638:Norepinephrine