Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>

ABSTRACT The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients i...

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Autores principales:	Brooke A. Napier, Eileen M. Burd, Sarah W. Satola, Stephanie M. Cagle, Susan M. Ray, Patrick McGann, Jan Pohl, Emil P. Lesho, David S. Weiss
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ac330734cff64b0791085f99705e75fc
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spelling	oai:doaj.org-article:ac330734cff64b0791085f99705e75fc2021-11-15T15:40:06ZClinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>10.1128/mBio.00021-132150-7511https://doaj.org/article/ac330734cff64b0791085f99705e75fc2013-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00021-13https://doaj.org/toc/2150-7511ABSTRACT The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic. IMPORTANCE Increased use of the cationic antibiotic colistin to treat multidrug-resistant Acinetobacter baumannii has led to the development of colistin-resistant strains. Here we report that treatment of patients with colistin can induce not only increased resistance to colistin but also resistance to host cationic antimicrobials. This worrisome finding likely represents an example of a broader trend observed in other bacteria against which colistin is used therapeutically such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Furthermore, these data suggest that the possible future use of an array of cationic antimicrobial peptides in development as therapeutics may have unintended negative consequences, eventually leading to the generation of hypervirulent strains that are resistant to innate host defenses. The potential for the induction of cross-resistance to innate immune antimicrobials should be considered during the development of new therapeutics.Brooke A. NapierEileen M. BurdSarah W. SatolaStephanie M. CagleSusan M. RayPatrick McGannJan PohlEmil P. LeshoDavid S. WeissAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 3 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Brooke A. Napier Eileen M. Burd Sarah W. Satola Stephanie M. Cagle Susan M. Ray Patrick McGann Jan Pohl Emil P. Lesho David S. Weiss Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
description	ABSTRACT The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This problem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human pathogen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly common. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic antimicrobials of the innate immune system. We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colistin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic. IMPORTANCE Increased use of the cationic antibiotic colistin to treat multidrug-resistant Acinetobacter baumannii has led to the development of colistin-resistant strains. Here we report that treatment of patients with colistin can induce not only increased resistance to colistin but also resistance to host cationic antimicrobials. This worrisome finding likely represents an example of a broader trend observed in other bacteria against which colistin is used therapeutically such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Furthermore, these data suggest that the possible future use of an array of cationic antimicrobial peptides in development as therapeutics may have unintended negative consequences, eventually leading to the generation of hypervirulent strains that are resistant to innate host defenses. The potential for the induction of cross-resistance to innate immune antimicrobials should be considered during the development of new therapeutics.
format	article
author	Brooke A. Napier Eileen M. Burd Sarah W. Satola Stephanie M. Cagle Susan M. Ray Patrick McGann Jan Pohl Emil P. Lesho David S. Weiss
author_facet	Brooke A. Napier Eileen M. Burd Sarah W. Satola Stephanie M. Cagle Susan M. Ray Patrick McGann Jan Pohl Emil P. Lesho David S. Weiss
author_sort	Brooke A. Napier
title	Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_short	Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_full	Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_fullStr	Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_full_unstemmed	Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_sort	clinical use of colistin induces cross-resistance to host antimicrobials in <named-content content-type="genus-species">acinetobacter baumannii</named-content>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/ac330734cff64b0791085f99705e75fc
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Clinical Use of Colistin Induces Cross-Resistance to Host Antimicrobials in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>

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