impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among canadian community and health-care associated methicillin-resistant staphylococcus aureus附属基因的影响调节器(agr)功能障碍万古霉素药效学在加拿大社区和卫生保健相关的耐甲氧西林金黄色葡萄球菌.pdfVIP

Tsuji et al. Annals of Clinical Microbiology and Antimicrobials 2011, 10:20 /content/10/1/20 RESEARCH Open Access Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus 1,2,3* 1,4 4 5,6 5,6 Brian T Tsuji , Robert D MacLean , Linda D Dresser , Martin J McGavin and Andrew E Simor Abstract Background: The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA. Methods: 40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 106 and 108 cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model. Results: 15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 106 cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 108 cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (E