Vancomycin resistance emerging

Link: Relationships between vancomycin pharmacodynamics and the emergence of vancomycin-intermediate Staphylococcus aureus (VISA) from heterogeneous VISA in an in vitro pharmacodynamic model -- Rose et al., 10.1093/jac/dkn037 -- Journal of Antimicrobial Chemotherapy.

Results: The activity of vancomycin was highly dependent on the bacterial inoculum. At high inoculum, all vancomycin simulations displayed initial killing up to 24 h with no additional activity beyond this time point. Increased vancomycin doses had no impact on overall activity. Although bactericidal activity was achieved in all strains, regardless of the presence of hVISA, ~105cfu/mL of organisms remained after exposure. Doses as high as 5 g every 12 h (fAUC/MIC 799) had little influence on decreasing the hVISA bacterial load. More rapid bactericidal eradication was noted at lower inoculum in the non-hVISA isolate (T99 1.9 h versus 14.1 h and 15.3 h for Mu3 and 1629, respectively; P = 0.001). A 2- to 4-fold increase in vancomycin MIC was noted with both hVISA isolates compared with no increase in non-hVISA at high inoculum. Conclusions: Vancomycin doses ≥2500 mg and 2000 mg every 12 h (fAUC/MIC 374 and 271) suppressed the emergence of MIC increases in Mu3 and 1629, respectively. Our data suggest that at high inoculum, vancomycin has minimal to no activity against hVISA and leads to further reduced susceptibility.