某些类别的抗生素显示出“浓度依赖性”抗菌活性;较高的浓度导致细菌杀灭率增加,与“时间依赖性抗生素”相反,其显示的抗微生物活性取决于抗生素浓度保持在MIC以上的时间。氨基糖苷类和氟喹诺酮类仍然是广泛使用的浓度依赖性抗生素。这些抗生素不被β-内酰胺酶水解,对接种效果不太敏感,其可以被定义为在相对较高的细菌负荷(接种物)存在下对抗生素的增加的MIC。此外,它们具有相对较长的抗生素后效应(PAE),这可以定义为当抗生素浓度低于MIC时没有细菌生长。这些特征使它们在多重耐药(MDR)细菌和/或严重脓毒症(中性粒细胞减少)患者的管理中具有有趣的补充抗生素。全球监测研究表明,高达90%的MDR革兰氏阴性菌仍然对氨基糖苷类敏感,取决于敏感性断点(例如,CLSI或EUCAST)正在应用。氟喹诺酮类药物的这一百分比明显较低,但取决于地区,有机体的类型,和抗性机制有关。每日(高剂量)氨基糖苷类的剂量少于一周与显着降低的肾/耳托毒性和改善的目标达成相关。此外,氟喹诺酮类药物高于常规给药剂量与改善临床结局相关.β-内酰胺抗生素是推荐的治疗严重脓毒症的骨干。因为这些抗生素是时间依赖性的,添加第二种浓度依赖性抗生素可以迅速降低细菌接种物,创建PAE,并降低青霉素结合蛋白(PBP)的表达。感染部位的抗生素水平不足,尤其是在高接种物感染的情况下,已被证明是耐药抑制不足和治疗失败的重要危险因素。因此,在严重脓毒症的早期阶段,应努力优化剂量并迅速降低接种量。在这篇文章中,作者提出了“基于接种物的给药”的新概念,其中抗生素给药方案和/或联合治疗的决定不仅基于患者的PK参数,而且还取决于假定的接种物大小。一旦接种物降低,通过临床改善间接反映,应考虑简化治疗以进一步治疗感染。
Certain classes of antibiotics show \"concentration dependent\" antimicrobial activity; higher concentrations result in increased bacterial killing rates, in contrast to \"time dependent antibiotics\", which show antimicrobial activity that depends on the time that antibiotic concentrations remain above the MIC. Aminoglycosides and fluoroquinolones are still widely used concentration-dependent antibiotics. These antibiotics are not hydrolyzed by beta-lactamases and are less sensitive to the inoculum effect, which can be defined as an increased MIC for the antibiotic in the presence of a relatively higher bacterial load (inoculum). In addition, they possess a relatively long Post-Antibiotic Effect (PAE), which can be defined as the absence of bacterial growth when antibiotic concentrations fall below the MIC. These characteristics make them interesting complementary antibiotics in the management of Multi-Drug Resistant (MDR) bacteria and/or (neutropenic) patients with severe sepsis. Global surveillance studies have shown that up to 90% of MDR Gram-negative bacteria still remain susceptible to aminoglycosides, depending on the susceptibility breakpoint (e.g., CLSI or EUCAST) being applied. This percentage is notably lower for fluoroquinolones but depends on the region, type of organism, and mechanism of resistance involved. Daily (high-dose) dosing of aminoglycosides for less than one week has been associated with significantly less nephro/oto toxicity and improved target attainment. Furthermore, higher-than-conventional dosing of fluoroquinolones has been linked to improved clinical outcomes. Beta-lactam antibiotics are the recommended backbone of therapy for severe sepsis. Since these antibiotics are time-dependent, the addition of a second concentration-dependent antibiotic could serve to quickly lower the bacterial inoculum, create PAE, and reduce Penicillin-Binding Protein (PBP) expression. Inadequate antibiotic levels at the site of infection, especially in the presence of high inoculum infections, have been shown to be important risk factors for inadequate resistance suppression and therapeutic failure. Therefore, in the early phase of severe sepsis, effort should be made to optimize the dose and quickly lower the inoculum. In this article, the authors propose a novel concept of \"Inoculum Based Dosing\" in which the decision for antibiotic dosing regimens and/or combination therapy is not only based on the PK parameters of the patient, but also on the presumed inoculum size. Once the inoculum has been lowered, indirectly reflected by clinical improvement, treatment simplification should be considered to further treat the infection.