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住院马的庆大霉素血药浓度和回顾性革兰氏阴性马病原体最低抑菌浓度。

Gentamicin plasma concentrations in hospitalized horses and retrospective minimal inhibitory concentrations of gram-negative equine pathogens.

机构信息

Vetsuisse Faculty, Equine Department, Clinic for Equine Internal Medicine, University of Zurich, Zurich, Switzerland.

Vetsuisse Faculty, Institute of Veterinary Bacteriology, University of Zurich, Zurich, Switzerland.

出版信息

J Vet Emerg Crit Care (San Antonio). 2021 May;31(3):323-330. doi: 10.1111/vec.13035. Epub 2020 Dec 4.

Abstract

OBJECTIVES

The optimal dosage regimen of gentamicin in horses is still under investigation. The objectives of this study were to determine gentamicin plasma concentrations in hospitalized horses treated with 10 mg/kg gentamicin (IV, q 24 h) and to determine whether a plasma concentration to minimum inhibitory concentration (MIC) ratio of 10:1 is reached for equine pathogens using this dose.

DESIGN

Prospective clinical observational study; retrospective study on MICs of 131 gram-negative bacteria isolated from horses (2012-2015).

SETTING

University teaching hospital.

ANIMALS

Ninety-eight horses >6 months old, treated with gentamicin for their primary disease, consecutive samples.

MEASUREMENTS AND MAIN RESULTS

Plasma concentrations were measured 1 hour (C ) and 20 hours (C ) after gentamicin administration using fluorescence polarization. Presence of systemic inflammatory response syndrome (SIRS) and azotemia was recorded, as well as the reason for antimicrobial administration (primary disease) and whether administration was prophylactic or therapeutic. The target C of ≥20 µg/mL gentamicin was reached in 90% of horses and was sufficient to reach a plasma concentration:MIC of 10:1 in 32 of 131 (24%) of gram-negative aerobic bacteria. A C ≤ 2 µg/mL was reached in 97% horses. Therapeutic versus prophylactic administration, primary disease, azotemia, and systemic inflammatory response syndrome were not associated with a failure to reach a desired peak or trough.

CONCLUSIONS

The gentamicin dose of 10 mg/kg every 24 hours should be further investigated and safety assessed because a target gentamicin plasma concentration of ≥20 µg/mL was achieved in the majority of cases. Nephrotoxic side effects were not assessed. Individual drug monitoring should be performed because clinical factors are unreliable predictors of plasma concentrations. A gentamicin target concentration of ≥40 µg/mL does not offer additional benefits compared to ≥20 µg/mL, due to the bimodal distribution of resistance in bacterial isolates.

摘要

目的

庆大霉素在马中的最佳剂量方案仍在研究中。本研究的目的是确定接受 10mg/kg 庆大霉素(IV,q24h)治疗的住院马匹的庆大霉素血浆浓度,并确定使用该剂量是否达到马病原体的血浆浓度与最小抑菌浓度(MIC)比值为 10:1。

设计

前瞻性临床观察研究;2012-2015 年从马分离的 131 株革兰氏阴性菌 MIC 的回顾性研究。

设置

大学教学医院。

动物

98 匹>6 个月大的马,因原发性疾病接受庆大霉素治疗,连续采样。

测量和主要结果

使用荧光偏振法测量庆大霉素给药后 1 小时(C )和 20 小时(C )的血浆浓度。记录是否存在全身炎症反应综合征(SIRS)和氮质血症,以及使用抗菌药物的原因(原发性疾病)以及给药是预防还是治疗。90%的马匹达到了目标 C ≥20μg/ml 的庆大霉素,足以使 32/131(24%)株革兰氏阴性需氧菌的血浆浓度:MIC 达到 10:1。97%的马匹达到 C ≤2μg/ml。达到期望的峰或谷浓度与治疗与预防给药、原发性疾病、氮质血症和全身炎症反应综合征无关。

结论

由于大多数情况下达到了目标庆大霉素血浆浓度≥20μg/ml,应进一步研究和评估 10mg/kg 每 24 小时的庆大霉素剂量,并且要评估肾毒性副作用。由于细菌分离株的耐药性呈双峰分布,因此与≥20μg/ml 相比,≥40μg/ml 的庆大霉素目标浓度不会带来额外的益处,因此应进行个体药物监测,因为临床因素不可靠地预测血浆浓度。

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