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]
Summary
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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