FDA批准tedizolid用于急性细菌性皮肤感染

美国食品药品管理局（FDA）6月20日宣布，恶唑烷酮类抗菌药tedizolid（Sivextro）已获准作为静脉和口服药物用于革兰氏阳性菌引起的急性细菌性皮肤和皮肤组织感染（ABSSSI）的治疗，包括耐甲氧西林和甲氧西林敏感金葡菌、各种链球菌和粪肠球菌引起的ABSSSI。

在3月份召开的会议上，FDA抗感染药品专家组一致推荐批准tedizolid。该药物是FDA上月以来批准的第二个用于治疗ABSSSI的抗菌新药。5月23日，FDA批准了达巴万星（Dalvance）用于金葡菌和各种链球菌引起的ABSSSI治疗。这两种药物均被授予合格感染性疾病产品（QIDP）资格，允许其具有额外5年的市场独占权。

Tedizolid有效性和安全性评价试验表明，在1,315例成人患者随机接受tedizolid和利奈唑胺治疗的2项临床试验中，tedizolid与利奈唑胺等效。

在其中一项国际多中心随机III期研究（ESTABLISH-2）中，比较了666例ABSSSI患者接受6天tedizolid静注和10天利奈唑胺静注治疗情况，并允许患者改用口服治疗。患者病灶面积≥75 cm²，确认或疑似与革兰氏阳性菌感染有关。半数患者患有蜂窝组织炎，20%为大脓肿，约30%为伤口感染，约27%为耐甲氧西林金葡菌（MRSA）感染。

85% 和83%的tedizolid和利奈唑胺治疗患者分别达到主要终点指标，即早期临床反应（开始治疗后48~72小时病灶面积减少≥20%），两组差异符合非劣性界值。7~14天临床反应也相似。在后期随访中，结束治疗18~25天MRSA感染结局与总体结果一致。上述研究结果在线发表在《柳叶刀·传染病》杂志上。

Tedizolid治疗患者出现胃肠道相关不良事件的比例（16%）略少于利奈唑胺治疗患者（20%），其他与治疗相关的不良事件相似。

FDA声明指出，尚未对中性粒细胞减少症患者进行tedizolid 评价研究，因此这类患者应考虑其他替代治疗。

Sivextro由卡毕斯特（Cubist）制药公司上市销售。

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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

Tedizolid, an oxazolidinone antibacterial drug, has been approved as an intravenous and oral treatment for acute bacterial skin and skin structure infections caused by gram positive bacteria, the Food and Drug Administration announced on June 20.

Tedizolid (Sivextro) is approved to treat patients with acute bacterial skin and skin structure infections (ABSSSI) caused by methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus, various streptococcus species, and Enterococcus faecalis.

At a meeting in March, the FDA’s Anti-infective Drugs Advisory Committee unanimously recommended that tedizolid be approved. The drug is the second new antibacterial drug to be approved by the FDA in the past month to treat ABSSSI. On May 23, the agency approved dalbavancin (Dalvance) to treat patients with ABSSSI caused by Staphylococcus aureus and various streptococcus species. Both drugs were designated as qualified infectious disease products, allowing them an additional 5 years of marketing exclusivity.

Tedizolid’s safety and efficacy were evaluated and shown to be as effective as linezolid in two clinical trials with 1,315 adults randomly assigned to receive tedizolid or linezolid.

One of the phase III studies, the ESTABLISH-2 study, an international, randomized study, compared 6 days of treatment with intravenous tedizolid to 10 days of treatment with IV linezolid in 666 patients with acute bacterial skin and skin structure infections, with the option of switching to oral treatment. The lesions were at least 75 cm² in size, and were known to be or were suspected to be associated with gram-positive bacteria. Half the patients had cellulitis, 20% had a major cutaneous abscess, and about 30% had an infected wound; about 27% had MRSA.

The primary endpoint, an early clinical response (at least a 20% reduction in the lesion area 48-72 hours after starting treatment), was achieved by 85% of those treated with tedizolid and by 83% of those treated with linezolid, a difference that met the non-inferiority margin. Clinical responses were also similar at 7-14 days. At late follow-up, 18-25 days after the end of treatment, outcomes of MRSA infections "matched the overall results," according to the study, which was published online in the Lancet Infectious Diseases.

Fewer patients on tedizolid (16%) developed gastrointestinal-related adverse events than those on linezolid (20%); otherwise, treatment- associated adverse events were similar in the two groups.

Tedizolid has not been evaluated in neutropenic patients, so alternative therapies should be considered, the FDA said in its statement announcing the approval.

Sivextro is marketed by Cubist Pharmaceuticals.