Adjunctive #transferrin to reduce the emergence of #antibiotic #resistance in Gram-negative #bacteria (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

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

Brian M Luna, Ksenia Ershova, Jun Yan, Amber Ulhaq, Travis B Nielsen, Sarah Hsieh, Paul Pantapalangkoor, Brian Vanscoy, Paul Ambrose, Sue Rudin, Kristine Hujer, Robert A Bonomo, Luis Actis, Eric P Skaar, Brad Spellberg

Journal of Antimicrobial Chemotherapy, dkz225, https://doi.org/10.1093/jac/dkz225

Published: 06 June 2019

 

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.

Topic: antibiotics – iron – antibiotic resistance, bacterial – ciprofloxacin – gram-negative bacteria – transferrin – meropenem – malnutrition-inflammation-cachexia syndrome

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Meropenem; Ciprofloxacin; Transferrin.

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