FDA批准第4个抗生素制剂用于复杂性尿路感染和腹腔感染

美国食品药品管理局（FDA）12月19日宣布，含有头孢类抗生素和β-内酰胺酶抑制剂的静脉注射用复方制剂获准用于治疗成人复杂性腹腔内感染和复杂性尿路感染。

其中头孢类抗生素为ceftolozane，β-内酰胺酶抑制剂为他唑巴坦，该药品将由卡毕斯特制药公司以商品名Zerbaxa上市。

据FDA声明，该药品是FDA 2014年批准的第4个抗生素类药品，与其他3个药品相似，该药品被认定为合格感染性疾病产品（QIDP）并授予优先审评资格。声明指出，按照《FDA安全与创新法案》之《开发新型抗生素激励（GAIN）法案》，Zerbaxa被认定为QIDP，“是因为该品是一种用于治疗严重或危及生命感染的抗生素或抗真菌人用药品。”

作为QIDP资格的一部分，FDA还授予制造商额外5年的“独占权”（市场独占权）。

Ceftolozane-他唑巴坦获准与甲硝唑合用治疗复杂性腹腔感染，该适应症获批是基于一项979例成人患者随机接受联合用药或美罗培南治疗的研究结果。

获准用复杂性尿路感染（包括肾盂肾炎），是基于一项1,068例成人患者随机接受Ceftolozane-他唑巴坦或左氧氟沙星治疗的研究结果。

该药品处方信息中包括了一项有关肾损害（基线肌酐清除率≤30-50 mL/min）患者疗效下降的警告，并建议“对肾功能变化患者至少每天”监测肌酐清除率，并相应调整剂量。据FDA声明，研究中最常见的不良事件包括恶心、腹泻、头痛和发热。

FDA在2014年批准的其他抗生素为治疗由某些敏感细菌引起的急性皮肤及皮肤组织感染的药品，包括5月份批准的达巴万星（Dalvance）、6月份批准的泰地唑利（Sivextro） 以及8月份批准的奥利万星（Dalvance）。

与Zerbaxa相关的严重不良事件应通过800-332-1088或www.fda.gov/Safety/MedWatch/HowToReport/default.htm报告至MedWatch系统。

By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

A combination of a cephalosporin and a beta-lactamase inhibitor in an intravenous formulation has been approved for treating complicated intra-abdominal infections and complicated urinary tract infections in adults, the Food and Drug Administration announced on Dec. 19.

The cephalosporin is ceftolozane and the beta-lactamase inhibitor is tazobactam; it will be marketed as Zerbaxa by Cubist Pharmaceuticals.

This is the fourth antibacterial drug product approved by the FDA in 2014 and, like the other three, it was designated as a Qualified Infectious Disease Product (QIDP) and was given priority review, according to the FDA statement. Zerbaxa was granted a QIDP designation under the Generating Antibiotic Incentives Now (GAIN) Act of the FDA Safety and Innovation Act, “because it is an antibacterial or antifungal human drug intended to treat a serious or life-threatening infection,” the statement said.

As part of the QIDP program, the manufacturer has also been granted an extra 5 years of “exclusivity” – exclusive marketing rights – by the FDA.

Ceftolozane-tazobactam was approved for treating complicated intra-abdominal infections in combination with metronidazole; approval for this indication was based on a study of 979 adults, randomized to the combination or to meropenem.

Approval for complicated urinary tract infections, including pyelonephritis, was based on a study of 1,068 adults, randomized to treatment with ceftolozane-tazobactam or levofloxacin.

The prescribing information includes a warning about decreased efficacy in patients with renal impairment (a baseline creatinine clearance of 30-50 mL/min or less, and the recommendation to monitor creatinine clearance “at least daily in patients with changing renal function,” and to adjust dose accordingly. Nausea, diarrhea, headache, and fever were the most common adverse events in studies, according to the FDA statement.

The other antibacterials approved by the FDA in 2014 were approved for treating acute bacterial skin and skin structure infections caused by certain susceptible bacteria. They were dalbavancin (Dalvance), approved in May; tedizolid (Sivextro), approved in June; and oritavancin (Orbactiv), approved in August.

Serious adverse events associated with Zerbaxa should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/HowToReport/default.htm.