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Vancomycin: The Tale of the Vanquisher and the Pyrrhic Victory

机译:万古霉素:胜利者的故事和止血的胜利

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摘要

Vancomycin has been the antibiotic of choice in the treatment of methicillin-resistant Staphylococcus aureus infections for decades. But relatively recently, vancomycin-intermediate-susceptible S. aureus (VISA) have been reported. Phenotypically, VISA are characterized by thicker cell walls, requiring higher concentrations of vancomycin for inhibition of bacterial cell growth. Vancomycin-intermediate-susceptible S. aureus represent just the tip of the iceberg of an insidious loss of vancomycin susceptibility in staphylococci. Increasing proportions of S. aureus isolates have higher minimum inhibitory concentrations that are still within the officially susceptible range, a characteristic that is associated with treatment failure. The most important risk factor for decreased vancomycin susceptibility is in vivo selection pressure. To prevent the development of VISA, prolonged or inappropriate use of vancomycin and suboptimal vancomycin levels should be avoided. Trough serum vancomycin concentrations of 15 - 20 mg/L for intermittent dosing and plateau serum vancomycin concentrations of 20 - 25 mg/L for continuous infusions are therefore currently recommended. The widespread clinical application of these intensive dosing regimens has resulted in an increasing awareness of vancomycin-induced nephrotoxicity, which is especially relevant in patients whose renal function is already compromised. This narrow therapeutic-toxic window reinforces the use of rigorous dosing protocols. In hemodialysis, the use of a vancomycin dose calculator permits achievement of target concentrations in most patients. In peritoneal dialysis (PD), intermittent vancomycin dosing regimens often lead to low end-of-dwell concentrations. On the other hand, a continuous vancomycin dosing regimen after a loading dose offers the desired combination of high local levels without toxic systemic levels.
机译:数十年来,万古霉素一直是耐甲氧西林金黄色葡萄球菌感染的首选抗生素。但相对较近的报道是,对万古霉素敏感的金黄色葡萄球菌(VISA)。从表型上说,VISA的特征是细胞壁更厚,需要更高浓度的万古霉素来抑制细菌细胞的生长。对万古霉素敏感的金黄色葡萄球菌只是葡萄球菌中对万古霉素敏感性的隐性丧失的冰山一角。增加比例的金黄色葡萄球菌具有更高的最低抑菌浓度,该浓度仍在官方易感范围内,这是与治疗失败有关的特征。万古霉素敏感性降低的最重要风险因素是体内选择压力。为防止发生VISA,应避免长时间或不适当使用万古霉素和次优万古霉素水平。因此,目前建议间歇给药的低谷万古霉素浓度为15-20 mg / L,连续输注的低谷血清万古霉素浓度为20-25 mg / L。这些密集给药方案的广泛临床应用导致对万古霉素诱导的肾毒性的认识不断提高,这在肾功能已经受损的患者中尤为重要。这种狭窄的治疗毒性窗口加强了严格剂量方案的使用。在血液透析中,使用万古霉素剂量计算器可以使大多数患者达到目标浓度。在腹膜透析(PD)中,间歇性万古霉素给药方案通常会导致低的终末浓度。另一方面,负荷剂量后的连续万古霉素给药方案提供了高局部水平的所需组合,而没有毒性全身水平。

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