Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which...

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Autores principales:	Christopher R Miller, Jonathan M Monk, Richard Szubin, Andrew D Berti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a91a1d38b1fb42798bf3dad5a385efb9
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spelling	oai:doaj.org-article:a91a1d38b1fb42798bf3dad5a385efb92021-12-02T20:16:45ZRapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.1932-620310.1371/journal.pone.0258592https://doaj.org/article/a91a1d38b1fb42798bf3dad5a385efb92021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258592https://doaj.org/toc/1932-6203Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.Christopher R MillerJonathan M MonkRichard SzubinAndrew D BertiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258592 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher R Miller Jonathan M Monk Richard Szubin Andrew D Berti Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
description	Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.
format	article
author	Christopher R Miller Jonathan M Monk Richard Szubin Andrew D Berti
author_facet	Christopher R Miller Jonathan M Monk Richard Szubin Andrew D Berti
author_sort	Christopher R Miller
title	Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
title_short	Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
title_full	Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
title_fullStr	Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
title_full_unstemmed	Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
title_sort	rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a91a1d38b1fb42798bf3dad5a385efb9
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Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.

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