近日，新型抗菌药物Sivextro(tedizolid phosphate)获美国FDA批准上市，用于治疗皮肤感染成人患者。Sivextro 被批准用于治疗由某些敏感细菌，如金黄色葡萄球菌（包括耐甲氧西林菌株和甲氧西林敏感菌株）、各种链球菌和粪肠球菌引起的急性细菌性皮肤及皮肤组织感染 (ABSSSI)。Sivextro 以静脉注射和口服给药。
FDA药品评价和研究中心的抗微生物产品室主任Edward Cox，M.D.，M.P.H说：“今天的批准提供医生和患者对严重有皮肤感染一种新治疗选择，”被指定为一种合格的传染病产品(QIDP)和接受一种加快审评。QIDP指定还使它合格对另外五年专卖权。
批准日期：2014年6月20日；公司：Cubist Pharmaceuticals，Inc./MERCK SHARP & DOHME
SIVEXTRO(磷酸泰地唑胺[TEDIZOLID PHOSPHATE])注射剂，为静脉使用
SIVEXTRO(磷酸泰地唑胺[TEDIZOLID PHOSPHATE])片剂，为口服使用
美国初次批准：2014
作用机制
Tedizolid磷酸酯是tedizolid的前药，一种抗细菌药[见药代动力学；微生物学].
适应证和用途
SIVEXTRO是一种恶唑烷酮类抗细菌药适用在成年为治疗由指定易感细菌所致急性细菌性皮肤和皮肤结构感染(ABSSSI)。
为减低耐药细菌的发生和维持SIVEXTRO和其他抗细菌药的有效性，SIVEXTRO只应用于治疗或预防被证明或强烈怀疑是被细菌所致感染。
剂量和给药方法
200 mg每天1次口服或作为静脉(IV)历时1小时输注给予共6天。
剂型和规格
⑴注射：200mg，无菌，冻干粉在为静脉输注重建单次使用小瓶；
⑵片：200mg
禁忌证
无
警告和注意事项
⑴患者有粒细胞减少：尚未曾适当地在有粒细胞减少(中性粒细胞计数<1000细胞/mm3)患者中评价SIVEXTRO的安全性和疗效。在一个感染的动物模型，SIVEXTRO的抗细菌活性在缺乏粒细胞时减低。中性粒细胞减少患者考虑替代疗法。
⑵难辨梭状芽孢杆菌[Clostridium difficile]-伴随腹泻：如发生腹泻评价。
不良反应
最常见不良反应(>2%)是恶心，头痛，腹泻，呕吐，和眩晕。
包装供应/贮存和处置
SIVEXTRO TAB 200MG UD6  TEDIZOLID PHOSPHATE  MERCK SHARP & DOHME  67919-0041-02
SIVEXTRO TAB 200MG 30  TEDIZOLID PHOSPHATE  MERCK SHARP & DOHME  67919-0041-01
SIVEXTRO 200MG SDV LYO PWD 10/PAC  TEDIZOLID PHOSPHATE  CUBIST PHARMACEUTICALS  67919-0040-01            
SIVEXTRO VIAL 200MG 10  TEDIZOLID PHOSPHATE  MERCK SHARP & DOHME  67919-0040-01 

贮存和处置
SIVEXTRO片和SIVEXTRO为注射应贮存在20°C至25°C (68°F至77°F)；外出允许至15°C至30°C (59°F至86°F) [见USP控制室温].

产品特点：
2014年6月20日，美国食品药品监督管理局（FDA）批准卡比斯特制药公司的Sivextro(tedizolid phosphate，磷酸特地唑胺)用于治疗成年人急性细菌性皮肤和皮肤组织感染(ABSSSIs)。医院获得性/呼吸机相关性细菌性肺炎（HABP/VABP）（临床II期）。
磷酸特地唑胺具体的目标是由革兰氏阳性细菌，包括：金黄色葡萄球菌（包括耐甲氧西林[MRSA]和甲氧西林敏感[MSSA]菌株），酿脓链球菌，无乳链球菌，咽峡炎链球菌群（包括咽峡炎链球菌，中间型链球菌和星群链球菌）以及粪肠球菌引起的感染。特地唑胺也是是继2000年辉瑞的Zyvox（linezolid，利奈唑胺）之后上市恶唑烷酮类抗生素的新成员，但其药效和副作用明显有所改善。
磷酸特地唑胺是特地唑胺的前药，口服或静脉给药后，通过磷酸酯酶转化成特地唑胺。特地唑胺是恶唑烷酮类抗生素，通过与细菌核糖体50S亚基结合，抑制细菌蛋白质合成，发挥抗菌作用，与其它类别的抗生素之间不易产生交叉耐药。本品与首个恶唑烷酮类抗生素利奈唑胺相比，在胃肠道和血小板减少方面的不良反应要比利奈唑胺少，耐药性的发生率也更低。FDA已批准的剂型有注射剂和片剂，方便临床切换，用法为每天一次共六天，比利奈唑胺的每天两次共十天更方便临床使用。
附其他治疗资料；
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=75672079-589f-451a-bdbf-eaebcfcc80a9
Sivextro(tedizolid phosphate)
General Information
Sivextro (tedizolid phosphate) is an antibacterial agent of the oxazolidinone class.
Sivextro is specifically indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus inosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.
Sivextro is supplied as a tablet or solution, for oral and/or intravenous administration. The recommended dosage of Sivextro is 200 mg administered once daily for six (6) days either orally (with or without food) or as an intravenous (IV) infusion.
Clinical Results
FDA Approval
The FDA approval of Sivextro was based on two multicenter, multinational, randomized, double-blind, non-inferiority trials. Both trials compared Sivextro 200 mg once daily for 6 days versus linezolid 600 mg every 12 hours for 10 days. In Trial 1, subjects were treated with oral therapy, while in Trial 2, subjects could receive oral therapy after a minimum of one day of intravenous therapy. Subjects with cellulitis/erysipelas, major cutaneous abscess, or wound infection were enrolled in the trials. Subjects with wound infections could have received aztreonam and/or metronidazole as adjunctive therapy for gram-negative bacterial coverage, if needed. The intent-to-treat (ITT) patient population included all randomized patients.
Trial 1
This trial randomized 323 subjects to Sivextro and 326 subjects to linezolid. The overall median surface area of infection was 190 cm2. The types of ABSSSI included were cellulitis/erysipelas (40%), wound infection (30%), and major cutaneous abscess (30%). In addition to local signs and symptoms of infection, subjects were required to have at least one regional or systemic sign of infection at baseline. The primary endpoint was early clinical response defined as no increase from baseline lesion area at 48-72 hours after the first dose and oral temperature of ≤37.6°C, confirmed by a second temperature measurement within 24 hours in the ITT population. The percentage of responders to the primary endpoint was 79.3% and 79.1% in the Sivextro and linezolid arms, respectively.
Trial 2
This trial randomized 332 subjects to Sivextro and 334 subjects to linezolid. The overall median surface area of infection was 231 cm2. The types of ABSSSI included were cellulitis/erysipelas (50%), wound infection (30%), and major cutaneous abscess (20%). In addition to local signs and symptoms of infection, subjects were also required to have at least one regional or systemic sign of infection at baseline. The primary endpoint was early clinical response defined as at least a 20% decrease from baseline lesion area at 48-72 hours after the first dose in the ITT population. The percentage of responders to the primary endpoint was 85.2% and 82.6% in the Sivextro and linezolid arms, respectively.
Side Effects
Adverse effects associated with the use of Sivextro may include, but are not limited to, the following:
nausea
headache
diarrhea
vomiting
dizziness
Mechanism of Action
Sivextro (tedizolid phosphate) is an antibacterial agent of the oxazolidinone class.The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely. The results of in vitro time-kill studies show that tedizolid is bacteriostatic against enterococci, staphylococci, and streptococci.