Catecholamine Inotrope Resuscitation of Antibiotic‐Damaged Staphylococci and Its Blockade by Specific Receptor Antagonists
1Department of Infection, Immunity and Inflammation, University of Leicester School of Medicine, and 2the Department of Genetics, University of Leicester, United Kingdom; 3Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, Lubbock, Texas
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.
Received 17 July 2007; accepted 1 November 2007; electronically published 29 February 2008.
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Potential conflicts of interest: none reported.
Financial support: Wellcome Trust (grant 064488/Z/01/Z to P.P.E.F.); National Institutes of Health (grant MH‐50431 to M.L.).