In this regard, a worrisome report on a transmissible vanA plasmid has been published [71]. Future prevalence of VRSA is not an illusion as long as we continue using vancomycin as the first choice for MRSA infection. We have to develop new chemotherapeutic agents against multi-resistant MRSA to prepare for the future. 3) ‘sVISA’

– an ingenious strategy to survive vancomycin chemotherapy Vancomycin is still the first-line antibiotic against MRSA infection. However, its clinical effectiveness is compromised even against the strains whose vancomycin MICs are within the CLSI susceptible TGFbeta inhibitor range (≤2 mg/L) [50] and [51]. Also, the overall therapeutic failure rates of vancomycin are too high to be explained by the latent infection of VRSA (with vancomycin MIC of ≥16 mg/L) or even of VISA (MIC ≥ 4 mg/L) [50], [67], [68] and [69]. It seems that many MRSA strains exist whose vancomycin MIC values are in susceptible range (≤2 mg/L), and yet ‘resisting’ vancomycin killing. hVISA is evidently one of those strains resisting vancomycin by generating VISA at high frequency. However, in this case, hVISA is converted to VISA during the therapy, and the therapeutic failure is ascribed to the VISA strain. In this case, VISA would be detected from clinical specimen after vancomycin

Cabozantinib datasheet therapy. Using hVISA strain Mu3, however, we noticed a transient VISA status designated ‘slow VISA (sVISA)’ which returns to hVISA quickly once vancomycin is removed from the culture [66]. This implies that hVISA infection may not leave VISA after unsuccessful vancomycin therapy. Only hVISA with susceptible levels of vancomycin MIC values would be present after vancomycin therapy. Fig. 4 illustrates the PA pattern of hVISA strain Mu3 evaluated after 2 days (Mu3-48 h) and 6 days (Mu3-144 h) of incubation at 37 °C. The usual PA test is evaluated after 2 days. However, when PA was evaluated

after 72 h (3 days) to 144 h (6 days) of incubation, additional number of Mu3 colonies appeared on the BHI agar plates containing 4 mg/L or greater concentrations of vancomycin (Fig. 2). In contrast VSSA strain ΔIP did not generate additional colonies after 48 h (Fig. 4). The number of the late-appearing colonies was comparable to the number of the colonies that had appeared within 48 h of incubation. VISA is Etofibrate included within the latter group of colonies, and sVISA was identified within the late-appearing colonies. The first sVISA strain Mu3-6R-P (6R-P) was obtained in vitro from hVISA strain Mu3 by the selection with 6 mg/L of vancomycin [52]. 6R-P grew extremely slowly, and did not draw our attention until recently. Then its high level of vancomycin resistance was noticed (MIC = 16 mg/L, with E-test evaluated after 72 h incubation [66].) The strain 6R-P had a VISA phenotype similar to the extant VISA strains; i.e., thickened cell wall and reduced autolytic activity.