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采用血浆中多粘菌素快速测定法成功治疗耐多药铜绿假单胞菌感染:治疗药物监测的实用性

Successful Colistin Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infection Using a Rapid Method for Determination of Colistin in Plasma: Usefulness of Therapeutic Drug Monitoring.

作者信息

Yamada Takehiro, Ishiguro Nobuhisa, Oku Kenji, Higuchi Issei, Nakagawa Ikuma, Noguchi Atsushi, Yasuda Shinsuke, Fukumoto Tatsuya, Iwasaki Sumio, Akizawa Kouji, Furugen Ayako, Yamaguchi Hiroaki, Iseki Ken

机构信息

Department of Pharmacy, Hokkaido University Hospital.

出版信息

Biol Pharm Bull. 2015;38(9):1430-3. doi: 10.1248/bpb.b15-00323. Epub 2015 Jul 9.

Abstract

A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to colistin. Therefore, in addition to these antibiotics, the administration of intravenous colistin methanesulfonate, a prodrug formula of colistin, was started at a daily dose of 2.5 mg/kg (as colistin base activity). The initial dose setting was based on the patient's renal function (baseline creatinine clearance=32.7 mL/min). After initiating colistin, the patient's C-reactive protein levels gradually decreased. Blood cultures showed no evidence of MDRP on days 8, 14, and 22 after colistin initiation. However, the patient's renal function went from bad to worse owing to septic shock induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. A few days later, the trough plasma levels of colistin were 7.88 mg/L, which appeared to be higher than expected. After decreasing the colistin dose, the patient's renal function gradually improved. On the final day of colistin treatment, the plasma levels decreased to 0.60 mg/L. MDRP could not be detected in blood culture after colistin treatment. Therefore, we successfully treated a case of bloodstream infection due to MDRP by therapeutic drug monitoring (TDM) of colistin. It is suggested that the monitoring of blood colistin levels by liquid chromatography-tandem mass spectrometry can contribute to safer, more effective antimicrobial therapy of MDRP because TDM facilitates quick decisions on dose adjustments.

摘要

一名56岁的系统性红斑狼疮女性患者发生了由多重耐药铜绿假单胞菌(MDRP)引起的菌血症。她最初接受亚胺培南 - 西司他丁、妥布霉素和氨曲南治疗;然而,其血浆中仍间歇性检测到MDRP。多重药敏试验表明,MDRP仅对黏菌素敏感。因此,除了这些抗生素外,开始静脉注射黏菌素甲磺酸盐(黏菌素的前体药物形式),每日剂量为2.5 mg/kg(以黏菌素碱活性计)。初始剂量设定基于患者的肾功能(基线肌酐清除率 = 32.7 mL/min)。开始使用黏菌素后,患者的C反应蛋白水平逐渐下降。在开始使用黏菌素后的第8天、14天和22天,血培养未发现MDRP迹象。然而,由于耐甲氧西林金黄色葡萄球菌(MRSA)感染引起的感染性休克,患者的肾功能每况愈下。几天后,黏菌素的血浆谷浓度为7.88 mg/L,似乎高于预期。降低黏菌素剂量后,患者的肾功能逐渐改善。在黏菌素治疗的最后一天,血浆浓度降至0.60 mg/L。黏菌素治疗后血培养未检测到MDRP。因此,我们通过对黏菌素进行治疗药物监测(TDM)成功治疗了一例由MDRP引起的血流感染病例。建议通过液相色谱 - 串联质谱法监测血液黏菌素水平有助于对MDRP进行更安全、有效的抗菌治疗,因为TDM有助于快速做出剂量调整决策。

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