McNeil J Chase, Sommer Lauren M, Vallejo Jesus G, Hulten Kristina G, Kaplan Sheldon L
Department of Pediatrics, Division of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA.
Texas Children's Hospital, Houston, Texas, USA.
Microbiol Spectr. 2023 Mar 2;11(2):e0333322. doi: 10.1128/spectrum.03333-22.
Many health care centers have reported an association between Staphylococcus aureus isolates bearing efflux pump genes and an elevated MIC/minimal bactericidal concentration (MBC) to chlorhexidine gluconate (CHG) and other antiseptics. The significance of these organisms is uncertain, given that their MIC/MBC is typically far lower than the CHG concentration in most commercial preparations. We sought to evaluate the relationship between carriage of the efflux pump genes and in S. aureus and the efficacy of CHG-based antisepsis in a venous catheter disinfection model. S. aureus isolates with and without and/or were utilized. The CHG MICs were determined. Venous catheter hubs were inoculated and exposed to CHG, isopropanol, and CHG-isopropanol combinations. The microbiocidal effect was calculated as the percent reduction in CFU following exposure to the antiseptic relative to the control. The and -positive isolates had modest elevations in the CHG MIC compared to the and -negative isolates (0.125 mcg/ml vs. 0.06 mcg/ml, respectively). However, the CHG microbiocidal effect was significantly lower for - and/or -positive strains than for susceptible isolates, even when the isolates were exposed to CHG concentrations up to 400 μg/mL (0.04%); this finding was most notable for isolates bearing both and (89.3% versus 99.9% for the and -negative isolates; = 0.04). Reductions in the median microbiocidal effect were also observed when these and -positive isolates were exposed to a solution of 400 μg/mL (0.04%) CHG and 70% isopropanol (89.5% versus 100% for the and -negative isolates; = 0.002). - and positive S. aureus isolates have a survival advantage in the presence of CHG concentrations exceeding the MIC. These data suggest that traditional MIC/MBC testing may underestimate the ability of these organisms to resist the effects of CHG. Antiseptic agents, including chlorhexidine gluconate (CHG), are commonly utilized in the health care environment to reduce rates of health care-associated infections. A number of efflux pump genes, including and , have been reported in Staphylococcus aureus isolates that are associated with higher MICs and minimum bactericidal concentrations (MBCs) to CHG. Several health care centers have reported an increase in the prevalence of these S. aureus strains following an escalation of CHG use in the hospital environment. The clinical significance of these organisms, however, is uncertain, given that the CHG MIC/MBC is far below the concentration in commercial preparations. We present the results of a novel surface disinfection assay utilizing venous catheter hubs. We found that -positive and -positive S. aureus isolates resist killing by CHG at concentrations far exceeding the MIC/MBC in our model. These findings highlight that traditional MIC/MBC testing is insufficient to evaluate susceptibility to antimicrobials acting on medical devices.
许多医疗保健中心报告称,携带外排泵基因的金黄色葡萄球菌分离株与葡萄糖酸氯己定(CHG)和其他防腐剂的最低抑菌浓度/最低杀菌浓度(MBC)升高之间存在关联。鉴于这些微生物的MIC/MBC通常远低于大多数商业制剂中的CHG浓度,其意义尚不确定。我们试图在静脉导管消毒模型中评估金黄色葡萄球菌中外排泵基因的携带情况与基于CHG的防腐效果之间的关系。使用了携带和不携带和/或的金黄色葡萄球菌分离株。测定了CHG的MIC。将静脉导管接头接种并暴露于CHG、异丙醇和CHG - 异丙醇组合中。杀菌效果以接触防腐剂后相对于对照的CFU减少百分比来计算。与和阴性分离株相比,和阳性分离株的CHG MIC有适度升高(分别为0.125 mcg/ml和0.06 mcg/ml)。然而,即使将分离株暴露于高达400μg/mL(0.04%)的CHG浓度下,和/或阳性菌株的CHG杀菌效果仍显著低于敏感分离株;这一发现对于同时携带和的分离株最为显著(和阴性分离株分别为89.3%和99.9%;P = 0.04)。当这些和阳性分离株暴露于400μg/mL(0.04%)CHG和70%异丙醇的溶液中时,也观察到中位杀菌效果降低(和阴性分离株分别为89.5%和100%;P = 0.002)。和阳性的金黄色葡萄球菌分离株在CHG浓度超过MIC时具有生存优势。这些数据表明,传统的MIC/MBC检测可能低估了这些微生物抵抗CHG作用的能力。防腐剂,包括葡萄糖酸氯己定(CHG)在内,常用于医疗保健环境中以降低医疗保健相关感染率。在金黄色葡萄球菌分离株中已报道了多种外排泵基因,包括和,这些基因与对CHG的更高MIC和最低杀菌浓度(MBC)相关。几家医疗保健中心报告称,在医院环境中CHG使用增加后,这些金黄色葡萄球菌菌株的流行率有所上升。然而,鉴于CHG的MIC/MBC远低于商业制剂中的浓度,这些微生物的临床意义尚不确定。我们展示了一项利用静脉导管接头的新型表面消毒试验的结果。我们发现,在我们的模型中,和阳性的金黄色葡萄球菌分离株在CHG浓度远超过MIC/MBC时能抵抗被杀死。这些发现突出表明,传统的MIC/MBC检测不足以评估对作用于医疗器械的抗菌药物的敏感性。