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J Antimicrob Chemother. 2019 Jun 6. pii: dkz225. doi: 10.1093/jac/dkz225. [Epub ahead of print]

Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria.

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Department of Medicine, Keck School of Medicine at the University of Southern California (USC), Los Angeles, CA, USA.
Molecular Microbiology and Immunology, Keck School of Medicine at the University of Southern California (USC), Los Angeles, CA, USA.
Institute for Clinical Pharmacodynamics, Schenectady, NY, USA.
Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA.
Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH, USA.
Department of Microbiology, Miami University, Oxford, OH, USA.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.



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.


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.


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.


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.


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.


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