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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.

Author information

1
Department of Medicine, Keck School of Medicine at the University of Southern California (USC), Los Angeles, CA, USA.
2
Molecular Microbiology and Immunology, Keck School of Medicine at the University of Southern California (USC), Los Angeles, CA, USA.
3
Institute for Clinical Pharmacodynamics, Schenectady, NY, USA.
4
Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA.
5
Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
6
Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH, USA.
7
Department of Microbiology, Miami University, Oxford, OH, USA.
8
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.

Abstract

BACKGROUND:

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.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
31170282
DOI:
10.1093/jac/dkz225

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