The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, β-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum β-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/β-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The β-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins. The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo β-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.

中文翻译：

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社区获得性尿路感染临床开发中的口服抗生素。

由于多药耐药、表达β-内酰胺酶的病原体的出现，尿路感染（UTI）的治疗变得复杂。由于治疗选择有限，患者经常需要住院和静脉注射治疗。从本质上讲，已经出现了对口服抗生素的强烈需求，这种抗生素对超广谱 β-内酰胺酶 (ESBL) 尿路病原体具有活性。口服碳青霉烯类药物（替比培南和硫培南）和口服头孢菌素/β-内酰胺酶抑制剂组合正处于临床开发的不同阶段，用于治疗简单和复杂的 UTI。如果获得批准，Tebipenem 将成为复杂性 UTI 的首个口服治疗药物，而 sulopenem 将用于非复杂性 UTI。β-内酰胺酶抑制剂 ETX0282、VNRX7145、ARX1796、和 QPX7728 与头孢泊肟酯或头孢布坦联合使用，与其他具有尿路病原体活性的口服头孢菌素相比，可在尿液中实现有利的暴露。头孢布烯-QPX7728 组合对碳青霉烯酶生产者（包括金属β-内酰胺酶生产者）具有潜在的广谱覆盖。其他新型组合，即头孢泊肟/ETX0282、头孢布烯/VNRX-7145 和头孢布烯/ARX1796，也对肺炎克雷伯菌碳青霉烯酶 (KPC) 和 OXA-48 样生产者表现出出色的活性。所有这些药剂，一旦进入商业用途，将加强门诊治疗。其他新型组合，即头孢泊肟/ETX0282、头孢布烯/VNRX-7145 和头孢布烯/ARX1796，也对肺炎克雷伯菌碳青霉烯酶 (KPC) 和 OXA-48 样生产者表现出出色的活性。所有这些药剂，一旦进入商业用途，将加强门诊治疗。其他新型组合，即头孢泊肟/ETX0282、头孢布烯/VNRX-7145 和头孢布烯/ARX1796，也对肺炎克雷伯菌碳青霉烯酶 (KPC) 和 OXA-48 样生产者表现出出色的活性。所有这些药剂，一旦进入商业用途，将加强门诊治疗。