In Vitro Studies of Pharmacodynamic Properties of Vancomycin against Staphylococcus aureus and Staphylococcus epidermidis

Abstract

The bactericidal activities of vancomycin against two reference strains and two clinical isolates of Staphylococcus aureusand Staphylococcus epidermidis were studied with five different concentrations ranging from 2× to 64× the MIC. The decrease in the numbers of CFU at 24 h was at least 3 log10CFU/ml for all strains. No concentration-dependent killing was observed. The postantibiotic effect (PAE) was determined by obtaining viable counts for two of the reference strains, and the viable counts varied markedly: 1.2 h for S. aureus and 6.0 h for S. epidermidis. The determinations of the PAE, the postantibiotic sub-MIC effect (PA SME), and the sub-MIC effect (SME) for all strains were done with BioScreen C, a computerized incubator for bacteria. The PA SMEs were longer than the SMEs for all strains tested. A newly developed in vitro kinetic model was used to expose the bacteria to continuously decreasing concentrations of vancomycin. A filter prevented the loss of bacteria during the experiments. One reference strain each of S. aureus andS. epidermidis and two clinical isolates of S. aureus were exposed to an initial concentration of 10× the MIC of vancomycin with two different half-lives (t 1/2s): 1 or 5 h. The post-MIC effect (PME) was calculated as the difference in time for the bacteria to grow 1 log10 CFU/ml from the numbers of CFU obtained at the time when the MIC was reached and the corresponding time for an unexposed control culture. The difference in PME between the strains was not as pronounced as that for the PAE. Furthermore, the PME was shorter when a t 1/2 of 5 h (approximate terminal t 1/2 in humans) was used. The PMEs at t 1/2s of 1 and 5 h were 6.5 and 3.6 h, respectively, for S. aureus. The corresponding figures for S. epidermidis were 10.3 and less than 6 h. The shorter PMEs achieved with at 1/2 of 5 h and the lack of concentration-dependent killing indicate that the time above the MIC is the parameter most important for the efficacy of vancomycin.

Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?

“…It is, however, bacteriostatic against enterococci. In in-vitro studies vancomycin shows no concentration-dependent killing effect and has a short to moderate postantibiotic effect against grampositive cocci [34]. Experimental models using neutropenic mice with peritonitis have, however, shown some concentration-dependent (C max /MIC) activity with advantages also evident when the area under the concentrationtime curve (AUC) to MIC ratio (AUC/MIC) is maximized [35].…”

Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods

“…Antibacterial activity S. aureus ATCC 29213 was used as a model strain to assess the antibacterial activity of VM formulated in Nano SD B. The minimal inhibitory concentration (MIC) of VM for S. aureus ATCC 29213 is 2 lg/mL, as previously reported [21]. A VM concentration greater 6.…”

Class-dependent relevance of tissue distribution in the interpretation of anti-infective pharmacokinetic/pharmacodynamic indices

“…This antibiotic class works by forming hydrogen bonds with bacterial cell wall intermediate peptides, thereby inhibiting peptidoglycan synthesis [99]. As characteristic for antibiotics that inhibit cell wall synthesis, the glycopeptides mainly display time-dependent killing in vitro [100][101][102][103][104]. However, oritavancin and dalbavancin have been shown to display bactericidal concentration-dependent activity in vitro [103,105].…”