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Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK.


ABSTRACT: Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections. Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.

SUBMITTER: Brazeau NF 

PROVIDER: S-EPMC7658547 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Loss of daptomycin susceptibility in clinical <i>Staphylococcus epidermidis</i> infection coincided with variants in <i>WalK</i>.

Brazeau Nicholas F NF   Levinson Kara J KJ   Schranz Asher A   Moser Kara A KA   Hollis Ian I   Iyer Prashanth P   Chien Christopher C   Bowen Amanda A   van Duin David D   Lachiewicz Anne A   Andermann Tessa T   Jones Melissa M   Miller Melissa M   Juliano Jonathan J JJ   Bartelt Luther A LA  

Evolution, medicine, and public health 20200907 1


Daptomycin (DAP) is key in treating multidrug-resistant <i>Staphylococcus</i> infections. Diminished susceptibility to DAP is emerging among <i>Staphylococcus epidermidis</i> strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent <i>S. epidermidis</i> bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, <i>WalK</i>,  ...[more]

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