We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria.
- Authors
Luna, Brian M; Ershova, Ksenia; Yan, Jun; Ulhaq, Amber; Nielsen, Travis B; Hsieh, Sarah; Pantapalangkoor, Paul; Vanscoy, Brian; Ambrose, Paul; Rudin, Sue; Hujer, Kristine; Bonomo, Robert A; Actis, Luis; Skaar, Eric P; Spellberg, Brad
- Abstract
<bold>Background: </bold>New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens-including Gram-negative bacteria-to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.<bold>Objectives: </bold>To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.<bold>Methods: </bold>The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time-kill assay and assays for the selection of resistant mutants.<bold>Results: </bold>We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time-kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.<bold>Conclusions: </bold>These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.
- Subjects
ACINETOBACTER baumannii; GRAM-negative bacteria; TRANSFERRIN; GRAM-negative bacterial diseases; DRUG resistance in bacteria; KLEBSIELLA pneumoniae; ANTIBIOTICS; PATHOGENIC microorganisms
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2019, Vol 74, Issue 9, p2631
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkz225