利奈唑胺严重与致死性不良反应——案例报道的汇总分析

doi:10.5246/jcps.2022.02.013

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (2): 153-161.DOI: 10.5246/jcps.2022.02.013

利奈唑胺严重与致死性不良反应——案例报道的汇总分析

裴彦宇¹, 郝继晖¹, 段文琪³, 郑宇静², 赵明², 杨莉萍²^,^*()

1. 北京市第六医院药剂科, 北京 100007
2. 北京医院药学部国家老年医学中心, 北京 100730
3. 北京市小汤山医院药剂科, 北京 102211

收稿日期:2021-08-15 修回日期:2021-10-26 接受日期:2021-11-12 出版日期:2022-02-27 发布日期:2022-02-25
通讯作者: 杨莉萍
作者简介:
+ Tel.: +86-13261055701, E-mail: 6yanyu16@sina.cn

Severe and lethal adverse reactions of linezolid—a summary analysis of case reports

Yanyu Pei¹, Jihui Hao¹, Wenqi Duan³, Yujing Zheng², Ming Zhao², Liping Yang²^,^*()

1 Department of Pharmacy, Beijing No. 6 Hospital, Beijing 100007, China
2 Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
3 Department of Pharmacy, Beijing Xiaotangshan Hospital, Beijing 102211, China

Received:2021-08-15 Revised:2021-10-26 Accepted:2021-11-12 Online:2022-02-27 Published:2022-02-25
Contact: Liping Yang

摘要/Abstract

摘要：

本研究通过系统汇总, 对利奈唑胺(Linezolid)引起不良反应(Adverse Drug Reactions, ADRs)的案例报告进行评价, 利奈唑胺ADRs对人体器官或系统的影响及其严重程度。检索PubMed、Embase、Cochrane图书馆、CINAH等电子数据库, 时间从数据库建立到2019年12月31日, 以"linezolid" + "case reports"和"利奈唑胺"+"案例"为检索词, 收集关于利奈唑胺ADRs的案例报告。共纳入个案报道159篇, 共计189例患者, 男女比例为0.89:1, 平均年龄(52.42 ± 23.43)岁。结果显示, 利奈唑胺引起的严重的ADRs主要发生在神经系统(n = 86)和血液系统(n = 44)中, 其次是代谢系统(n = 31)和胃肠道系统(n = 18), 其它系统的报道较少如皮肤组织(n = 6), 肾和泌尿系统(n = 3), 心血管系统(n = 2)和肝胆系统(n = 2)。报道最多的ADRs是5-羟色胺综合征(n = 40), 其次是视神经病变(n = 25)和血小板减少症(n = 22), 最严重的ADR是乳酸酸中毒(n = 29, 死亡占比达31.0%)。有11例血液系统ADRs患者基础即存在肾功能损伤的问题, 其中4例死亡; 血小板减少症的22例患者主要为65岁以上的老年人(n = 17), 还有1例新生儿和2例儿童。我们首次报道, 乳酸性酸中毒和血液系统ADRs多发生在28天内, 神经系统ADRs多发生在28天后; 而不可逆的听神经病变(n = 1)、低磷血症(n = 1)、心动过缓(n = 1)和未成年人牙齿变色(n = 5)是利奈唑胺说明书、相关指南和临床试验中没有描述过的ADRs。案例报道提示, 利奈唑胺最严重的ADRs是乳酸性酸中毒且多发生在28天内; 肾功能损伤和特殊人群可能是利奈唑胺发生血液系统ADRs的主要危险因素; 利奈唑胺相关ADRs罕见但已有听神经病变、低磷血症、心动过缓和未成年人牙齿变色的个案。

关键词: 利奈唑胺, 不良反应, 乳酸性酸中毒, 个案报道

Abstract:

A systematic summary was used to evaluate case reports of adverse drug reactions (ADRs) caused by linezolid, and to explore the effects and severity on human organs or systems in the real world. The databases, such as PubMed, Embase, Cochrane Library, and CINAHL, were searched using "linezolid" + "case reports" as search terms from the establishment of each database to 31st December 2019, and the case reports on ADRs related to linezolid were collected. A total of 159 case reports were finally included in the analysis, including 189 patients. The ratio of male to female was 0.89:1, and the average age was (52.42 ± 23.43) years old. The results showed that linezolid-related severe ADRs mainly occurred in the nervous system (n = 86) and blood system (n = 44), followed by the metabolic system (n = 31) and gastrointestinal system (n = 18). Other systems reported less frequently were the skin tissue (n = 6), renal and urinary system (n = 3), cardiovascular systems (n = 2), and hepatobiliary system (n = 2). The most common linezolid-related ADRs were serotonin syndrome (n = 40), followed by optic neuropathy (n = 25) and thrombocytopenia (n = 22). The most severe ADR was lactic acidosis (n = 29), and its death rate was as high as 31.0%. In the blood system ADRs, 11 cases had underlying diseases of renal impairment, and four of them died. Moreover, 22 cases with thrombocytopenia were mainly elderly over 65 years old (n = 17), and there were also one infant and one child with thrombocytopenia. We first reported that lactic acidosis and blood system ADRs mostly occurred within 28 d, and the nervous system ADRs mostly occurred after 28 d. Besides, irreversible auditory neuropathy (n = 1), hypophosphatemia (n = 1), bradycardia (n = 1), and tooth discoloration mostly occurring in minors (n = 5) were the linezolid-related ADRs, which were not described in the instructions, related guidelines, and clinical trials of linezolid. The most severe linezolid-related ADRs was lactic acidosis that occurred within 28 d. Renal damage and special populations might be the main risk factors in the blood system ADRs. Minor linezolid-related ADRs were rare, while there were still some cases of auditory neuropathy, hypophosphatemia, bradycardia, and tooth discoloration.

Key words: Linezolid, Adverse drug reactions, Lactic acidosis, Case reports

Supporting:

裴彦宇, 郝继晖, 段文琪, 郑宇静, 赵明, 杨莉萍. 利奈唑胺严重与致死性不良反应——案例报道的汇总分析[J]. 中国药学(英文版), 2022, 31(2): 153-161.

Yanyu Pei, Jihui Hao, Wenqi Duan, Yujing Zheng, Ming Zhao, Liping Yang. Severe and lethal adverse reactions of linezolid—a summary analysis of case reports[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(2): 153-161.

图/表 6

Figure 1. Flowchart of literature screening.

Figure 2. Publication time of included literature.

Table 1. Distribution of age and gender in patients.

Table 2. Distribution of linezolid-related ADRs in different durations of linezolid therapy.

Table 3. Summary of 189 case reports of linezolid-related ADRs in different systems/organs.

Table 4. Summary of 189 case reports of linezolid-related ADRs in different systems/organs.

参考文献 25

[1]	Norrby, R. Linezolid–a review of the first oxazolidinone. Expert. Opin. Pharmacother. 2001, 2, 293–302.
[2]	Tan, T.Q.; Yogev, R. Clinical pharmacology of linezolid: an oxazolidinone antimicrobial agent. Expert. Rev. Clin. Pharmacol. 2008, 1, 479–489.
[3]	Gerson, S.L.; Kaplan, S.L.; Bruss, J.B.; Le, V.; Arellano, F.M.; Hafkin, B.; Kuter, D.J. Hematologic effects of linezolid: summary of clinical experience. Antimicrob. Agents Chemother. 2002, 46, 2723–2726.
[4]	Meagher, A.K.; Forrest, A.; Rayner, C.R.; Birmingham, M.C.; Schentag, J.J. Population pharmacokinetics of linezolid in patients treated in a compassionate-use program. Antimicrob. Agents Chemother. 2003, 47, 548–553.
[5]	Gerson, S.L.; Kaplan, S.L.; Bruss, J.B.; Le, V.; Arellano, F.M.; Hafkin, B.; Kuter, D.J. Hematologic effects of linezolid: summary of clinical experience. Antimicrob. Agents Chemother. 2002, 46, 2723–2726.
[6]	Brennan, K.; Jones, B.L.; Jackson, L. Auditory nerve neuropathy in a neonate after linezolid treatment. Pediatr. Infect. Dis. J. 2009, 28, 169.
[7]	Tartarone, A.; Gallucci, G.; Iodice, G.; Romano, G.; Coccaro, M.; Vigliotti, M.L.; Mele, G.; Matera, R.; Renzo, N.D. Linezolid-induced bradycardia: a case report. Int. J. Antimicrob. Agents. 2004, 23, 412–413.
[8]	Miyawaki, A.; Ueda, T.; Nakao, A.; Adachi, M.; Ohya, M.; Yamada, I.; Takesue, Y.; Kotani, J. Linezolid-induced lactic acidosis followed by severe hypophosphatemia after discontinuation of linezolid. Surg. Infect. 2013, 14, 229–230.
[9]	Liu, C.; Bayer, A.; Cosgrove, S.E.; Daum, R.S.; Fridkin, S.K.; Gorwitz, R.J.; Kaplan, S.L.; Karchmer, A.W.; Levine, D.P.; Murray, B.E.; Rybak, M.J.; Talan, D.A.; Chambers, H.F. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant staphylococcus aureus infections in adults and children. Clin. Infect. Dis. 2011, 52, e18–e55.
[10]	Contou, D.; Fichet, J.; Grimaldi, D.; Cariou, A. Early life-threatening lactic acidosis following a single infusion of linezolid. Int. J. Antimicrob. Agents. 2011, 38, 84–85.
[11]	Narita, M.; Tsuji, B.T.; Yu, V.L. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2007, 27, 1189–1197.
[12]	Xiao, B.; Deng, P.; Jin, H.; Wang, H.; Cao, Y. Lactic acidosis and thrombocytopenia associated with linezolid therapy: a case report. Am. J. Case Rep. 2018, 19, 1117–1120.
[13]	Esnault, P.; Cotte, J.; Cungi, P.J.; Romanat, P.E.; Boret, H. Linezolid-induced hyperlactatemia in a burn patient. Ann. Françaises D'anesthésie et De Réanimation. 2013, 32, e117–e118.
[14]	Cheng, C.N.; Lin, S.W.; Wu, C.C. Early linezolid-associated lactic acidosis in a patient with Child’s class C liver cirrhosis and end stage renal disease. J. Infect. Chemother. 2018, 24, 841–844.
[15]	Gil Villar, M.P.; García Arguedas, C.; Santos Lasaosa, S.; Cía Blasco, P. Painful polyneuropathy secondary to prolonged treatment with linezolid: presentation of a case. Neurologia. 2012, 27, 443–445.
[16]	Gervasoni, C.; Bergia, R.; Cozzi, V.; Clementi, E.; Cattaneo, D. Is it time to revise linezolid doses in peritoneal dialysis patients? A case series. J. Antimicrob. Chemother. 2015, 70, 2918–2920.
[17]	Rodrigues, M.; Brito, M.; Villar, M.; Correia, P. Treatment of multidrug-resistant and extensively drug-resistant tuberculosis in adolescent patients. Pediatr. Infect. Dis. J. 2014, 33, 657–659.
[18]	Taguchi, K.; Miyakawa, T.; Ohmura, T.; Horio, M.; Anraku, Y.; Okada, T.; Mizuta, H.; Saito, H.; Kawaguchi, T. A reduced linezolid dosage maintains favorable efficacy with minimal hematologic toxicity in a methicillin-resistant Staphylococcus aureus-infected patient with renal insufficiency. Scand. J. Infect. Dis. 2013, 45, 77–80.
[19]	McNamee, W.B. Resumption of linezolid therapy after myelotoxicity. Clin. Infect. Dis. 2003, 37, 741–742.
[20]	Spellberg, B.; Yoo, T.; Bayer, A.S. Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6. J. Antimicrob. Chemother. 2004, 54, 832–835.
[21]	Lin, Y.H.; Wu, V.C.; Tsai, I.J.; Ho, Y.L.; Hwang, J.J.; Tsau, Y.K.; Wu, C.Y.; Wu, K.D.; Hsueh, P.R. High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency. Int. J. Antimicrob. Agents. 2006, 28, 345–351.
[22]	Soriano, A.; Ortega, M.; García, S.; Peñarroja, G.; Bové, A.; Marcos, M.; Martínez, J.C.; Martínez, J.A.; Mensa, J. Comparative study of the effects of pyridoxine, rifampin, and renal function on hematological adverse events induced by linezolid. Antimicrob. Agents Chemother. 2007, 51, 2559–2563.
[23]	Wu, V.C.; Wang, Y.T.; Wang, C.Y.; Tsai, I.J.; Wu, K.D.; Hwang, J.J.; Hsueh, P.R. High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease. Clin. Infect. Dis. 2006, 42, 66–72.
[24]	Parlak, E.; Tan, H. Pancytopenia due to linezolid treatment. Turk Pediatri Arsivi. 2015, 50, 185–188.
[25]	Tavil, B.; Balci, Y.I.; Yıldırım, I.; Tavil, Y.; Secmeer, G.; Ceyhan, M.; Tuncer, M. Linezolid-induced reversible bicytopenia in a 4-year-old boy with methicillin-resistant staphylococcus aureus bacteremia. Pediatr. Hematol. Oncol. 2008, 25, 67–71.

利奈唑胺严重与致死性不良反应——案例报道的汇总分析

Severe and lethal adverse reactions of linezolid—a summary analysis of case reports

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