Universidad Peruana Cayetano Heredia

Aminoglycoside-resistance gene signatures are predictive of aminoglycoside MICs for carbapenem-resistant Klebsiella pneumoniae.

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dc.contributor.author Huang, Yanqin
dc.contributor.author Rana, Amisha P.
dc.contributor.author Wenzler, Eric
dc.contributor.author Ozer, Egon A.
dc.contributor.author Krapp, Fiorella
dc.contributor.author Bulitta, Jürgen B.
dc.contributor.author Hauser, Alan R.
dc.contributor.author Bulman, Zackery P.
dc.date.accessioned 2022-02-01T21:18:28Z
dc.date.available 2022-02-01T21:18:28Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/11304
dc.description.abstract BACKGROUND: Aminoglycoside-containing regimens may be an effective treatment option for infections caused by carbapenem-resistant Klebsiella pneumoniae (CR-Kp), but aminoglycoside-resistance genes are common in these strains. The relationship between the aminoglycoside-resistance genes and aminoglycoside MICs remains poorly defined. OBJECTIVES: To identify genotypic signatures capable of predicting aminoglycoside MICs for CR-Kp. METHODS: Clinical CR-Kp isolates (n = 158) underwent WGS to detect aminoglycoside-resistance genes. MICs of amikacin, gentamicin, plazomicin and tobramycin were determined by broth microdilution (BMD). Principal component analysis was used to initially separate isolates based on genotype. Multiple linear regression was then used to generate models that predict aminoglycoside MICs based on the aminoglycoside-resistance genes. Last, the performance of the predictive models was tested against a validation cohort of 29 CR-Kp isolates. RESULTS: Among the original 158 CR-Kp isolates, 91.77% (145/158) had at least one clinically relevant aminoglycoside-resistance gene. As a group, 99.37%, 84.81%, 82.28% and 10.76% of the CR-Kp isolates were susceptible to plazomicin, amikacin, gentamicin and tobramycin, respectively. The first two principal components explained 72.23% of the total variance in aminoglycoside MICs and separated isolates into four groups with aac(6')-Ib, aac(6')-Ib', aac(6')-Ib+aac(6')-Ib' or no clinically relevant aminoglycoside-resistance genes. Regression models predicted aminoglycoside MICs with adjusted R2 values of 56%-99%. Within the validation cohort, the categorical agreement when comparing the observed BMD MICs with the predicated MICs was 96.55%, 89.66%, 86.21% and 82.76% for plazomicin, gentamicin, amikacin and tobramycin, respectively. CONCLUSIONS: Susceptibility to each aminoglycoside varies in CR-Kp. Detection of aminoglycoside-resistance genes may be useful to predict aminoglycoside MICs for CR-Kp en_US
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartofseries Journal of Antimicrobial Chemotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject gentamicin sulfate (usp) en_US
dc.subject amikacin en_US
dc.subject genes en_US
dc.subject gentamicins en_US
dc.subject klebsiella pneumoniae en_US
dc.subject tobramycin en_US
dc.subject aminoglycosides en_US
dc.subject linear regression en_US
dc.subject malnutrition-inflammation-cachexia syndrome en_US
dc.subject augmentative and alternative communication en_US
dc.subject carbapenem resistance en_US
dc.subject plazomicin en_US
dc.title Aminoglycoside-resistance gene signatures are predictive of aminoglycoside MICs for carbapenem-resistant Klebsiella pneumoniae. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1093/jac/dkab381
dc.relation.issn 1460-2091


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