Introduction

In Europe, non-typeable H. influenzae (NTHi) is the leading cause of invasive H. influenzae disease in adults and is associated with high mortality. The goal of this study was to determine whether current antimicrobial treatments for H. influenzae infection in Spain are suitable based on their probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets.

Methods

Pharmacokinetic parameters for the antibiotics studied (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, ceftriaxone, imipenem and ciprofloxacin) and susceptibility data for H. influenzae were obtained from literature. A Monte Carlo simulation was used to estimate the probability of target attainment (PTA), defined as the probability that at least a specific value of a PK/PD index is achieved at a certain MIC, and the cumulative fraction of response (CFR), defined as the expected population PTA for a specific drug dose and a specific microorganism population.

Results

Regardless of dosing regimen, all antibiotics yielded CFR values of 100% or nearly 100% for all strains, including BL+, BL− and BLNAR, except amoxicillin and ampicillin for BL+. Thus, if an infection is caused by BL+ strains, treatment with amoxicillin and ampicillin has a high probability of failure (CFR ≤ 8%). For standard doses of amoxicillin, amoxicillin/clavulanic acid and imipenem, PK/PD breakpoints were consistent with EUCAST clinical breakpoints. For the other antimicrobials, PK/PD breakpoints were higher than EUCAST clinical breakpoints.

Conclusions

Our study confirms by PK/PD analysis that, with the antimicrobials used as empirical treatment of invasive H. influenzae disease, a high probability of therapeutic success can be expected.

中文翻译：

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侵袭性流感嗜血杆菌感染抗菌治疗的充分性评价：药代动力学/药效学观点

介绍

在欧洲，不可分型流感嗜血杆菌(NTHi) 是成人侵袭性流感嗜血杆菌疾病的主要原因，并且与高死亡率相关。本研究的目的是根据达到药代动力学/药效学 (PK/PD) 目标的可能性，确定西班牙目前针对流感嗜血杆菌感染的抗菌治疗是否合适。

方法

研究的抗生素（阿莫西林、阿莫西林/克拉维酸、氨苄西林、头孢噻肟、头孢曲松、亚胺培南和环丙沙星）的药代动力学参数和流感嗜血杆菌的药敏数据均从文献中获得。使用蒙特卡罗模拟来估计目标实现概率 (PTA)，定义为在特定 MIC 和累积响应分数 (CFR) 下至少实现 PK/PD 指数特定值的概率，定义为特定药物剂量和特定微生物种群的预期种群 PTA。

结果

无论给药方案如何，除阿莫西林和氨苄青霉素外，所有抗生素对所有菌株（包括 BL+、BL- 和 BLNAR）的 CFR 值均为 100% 或接近 100%。因此，如果感染是由 BL+ 菌株引起的，用阿莫西林和氨苄西林治疗失败的可能性很高（CFR  ≤  8%）。对于标准剂量的阿莫西林、阿莫西林/克拉维酸和亚胺培南，PK/PD 折点与 EUCAST 临床折点一致。对于其他抗菌药物，PK/PD 折点高于 EUCAST 临床折点。

结论

我们的研究通过 PK/PD 分析证实，将抗菌药物用作侵袭性流感嗜血杆菌疾病的经验治疗，预计治疗成功的可能性很高。