期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 75, 期 9, 页码 2424-2431出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkaa221
关键词
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资金
- Departamento Administrativo de Ciencia, Tecnologia e Innovacion COLCIENCIAS [COL130874455850]
- Universidad El Bosque [PCI 9510-2017]
- NIH/NIAID [R01 AI134637, R21 AI143229, K24 AI121296]
- UTHealth Presidential Award
- University of Texas System STARS Award
- FONDECYT [1171805]
- Ministry of Education, Government of Chile
- Millennium Science Initiative, Ministry of Economy, Development and Tourism, Chile
Background: Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISA isolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures. Objectives: To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine Latin American countries. Methods: We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006-08 and 2011-14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection of hVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjected to population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogated alterations in predicted proteins associated with the development of the VISA phenotype in both hVISA and vancomycin-susceptible S. aureus (VSSA) genomes. Results: A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from 2006-08 and 2011-14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only 6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87-0.89) to the cut-off (0.9). The majority of the 39 hVISA isolates exhibited the Leu-14 -> Ile (90%) and VraT Glu-156 -> Gly (90%) amino acid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involving WalK, VraS, RpoB and RpoC proteins. Conclusions: The hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteins involved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest that Etest-based methods are an important alternative for the detection of hVISA clinical isolates.
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