Abstract

Vancomycin-intermediately resistant Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with treatment failure. hVISA contains only a subpopulation of cells with increased minimal inhibitory concentrations, and its detection is problematic because it is classified as vancomycin-susceptible by standard susceptibility testing and the gold-standard method for its detection is impractical in clinical microbiology laboratories. Recently, a research group developed a machine-learning classifier to distinguish VISA and hVISA from vancomycin-susceptible S. aureus (VSSA) according to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) data. Nonetheless, the sensitivity of hVISA classification was found to be 76%, and the program was not completely automated with a graphical user interface. Here, we developed a more accurate machine-learning classifier for discrimination of hVISA from VSSA and VISA among MRSA isolates in Japanese hospitals by means of MALDI-TOF MS data. The classifier showed 99% sensitivity of hVISA classification. Furthermore, we clarified the procedures for preparing samples and obtaining MALDI-TOF MS data and developed all-in-one software, hVISA Classifier, with a graphical user interface that automates the classification and is easy for medical workers to use; it is publicly available at https://github.com/bioprojects/hVISAclassifier. This system is useful and practical for screening MRSA isolates for the hVISA phenotype in clinical microbiology laboratories and thus should improve treatment of MRSA infections.

Highlights

  • Vancomycin has been the first-line drug for the treatment of methicillin-resistant S. aureus (MRSA) infections [1] prevalent worldwide [2]

  • Vancomycin-nonsusceptible MRSA infections are associated with greater rates of clinical treatment failure in comparison with vancomycinsusceptible S. aureus (VSSA) infections [3, 4]

  • Vancomycin-nonsusceptible MRSA can be classified into vancomycin-resistant S. aureus, vancomycin-intermediately resistant S. aureus (VISA), and heterogeneous Vancomycin-intermediately resistant Staphylococcus aureus (VISA), in which only a subpopulation of cells has minimal inhibitory concentrations (MICs) within the range indicative of intermediate resistance [5]

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Summary

Introduction

Vancomycin has been the first-line drug for the treatment of methicillin-resistant S. aureus (MRSA) infections [1] prevalent worldwide [2]. Vancomycin-nonsusceptible MRSA infections are associated with greater rates of clinical treatment failure in comparison with vancomycinsusceptible S. aureus (VSSA) infections [3, 4]. Vancomycin-nonsusceptible MRSA can be classified into vancomycin-resistant S. aureus, vancomycin-intermediately resistant S. aureus (VISA), and heterogeneous VISA (hVISA), in which only a subpopulation of cells has minimal inhibitory concentrations (MICs) within the range indicative of intermediate resistance [5]. The hVISA phenotype is thought to be an intermediate step in the evolution of VSSA to VISA for the development of resistance [6,7,8,9]. The detection of hVISA is known to be problematic because this phenotype is not detected by standard susceptibility testing; hVISA is classified as susceptible by the CLSI (Clinical & Laboratory Standards Institute) standards

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