Durlobactam/Sulbactam sodium

2026版更新的核心内容一、更新概览 2026年3月1日，美国感染病学会（IDSA）发布了《抗微生物药物耐药革兰阴性菌感染治疗指南》的2026年更新版（Version 5.0），该版本取代了此前所有早期版本。本次更新涵盖了六大类耐药病原体——产超广谱β-内酰胺酶肠杆菌目细菌（ESBL-E）、产AmpC β-内酰胺酶肠杆菌目细菌（AmpC-E）、碳青霉烯耐药肠杆菌目细菌（CRE）、难治性耐药铜绿假单胞菌（DTR P. aeruginosa）、碳青霉烯耐药鲍曼不动杆菌（CRAB）及嗜麦芽窄食单胞菌（S. maltophilia）——的治疗建议。 与2024版相比，2026版更新在以下方面有显著变化： ← 左右滑动查看完整表格 → 更新维度 核心变化 临床意义新型口服药物 纳入吉泊达星（gepotidacin，暂译）、匹美西林、硫培南三款新获批口服药物 显著扩展ESBL-E uUTI的口服治疗选择，减少碳青霉烯类使用新型BL/BLI组合 纳入头孢吡肟-恩美唑巴坦、氨曲南-阿维巴坦、静脉磷霉素 新增ESBL-E和NDM-E的靶向治疗选项AmpC-E风险分层 引入"中风险/低风险"二层分类，弃用传统SPACE/SPICE助记法 更精准的风险评估，指导抗生素选择CRAB治疗 延续舒巴坦-度洛巴坦联合碳青霉烯类为首选方案 强化ATTACK试验证据支持的首选地位S. maltophilia 氨曲南-阿维巴坦新增为推荐方案 填补了MBL产生菌株的治疗空白二、三款新型口服药物 2026版IDSA指南最重要的更新之一，是纳入三款在2024-2025年间获得FDA批准的新型口服抗菌药物，显著扩展了ESBL-E引起的非复杂性尿路感染（uUTI）的口服治疗选择。2.1 吉泊达星 吉泊达星是首个三氮杂苊烯类（triazaacenaphthylene）抗生素，于2025年3月获FDA批准用于uUTI治疗。其独特的作用机制是通过与DNA旋转酶和拓扑异构酶IV上的独特结合位点结合，抑制细菌DNA复制，因此即使存在对氟喹诺酮类耐药的靶点特异性突变，也不会导致对吉泊达星的交叉耐药。 体外活性：吉泊达星对超过90%的ESBL-E分离株具有活性。在两项随机对照临床试验（EAGLE-2和EAGLE-3）中，比较5日吉泊达星与5日呋喃妥因治疗ESBL产酶大肠埃希菌uUTI女性患者的疗效，吉泊达星组的治疗成功率数值上更优（第一项试验：70% [35/50] vs 63% [25/40]；第二项试验：68% [23/34] vs 40% [10/25]）。 指南推荐：吉泊达星与氨基糖苷类（单次剂量）、呋喃妥因、匹美西林、硫培南和甲氧苄啶-磺胺甲噁唑并列为ESBL-E所致uUTI的首选治疗选项。对于CRE所致uUTI，吉泊达星作为替代选项。最常见的不良事件为轻至中度腹泻。 剂量：uUTI：1.5 g口服，每12小时一次。2.2 匹美西林 匹美西林是一种口服青霉素类前体药物，在体内转化为活性成分美西林（mecillinam），已在国际市场使用数十年，于2024年4月在美国获批。其独特结构使其对大多数β-内酰胺酶不易成为底物。 体外活性：匹美西林对超过90%的ESBL-E分离株具有活性。三日疗程在uUTI女性患者中的治疗成功率约为75-95%。观察性研究提示ESBL-E uUTI的失败风险高于非ESBL-E uUTI，但更高剂量（400 mg每日三次）下未观察到这一差异。 指南推荐：匹美西林为ESBL-E所致uUTI的首选治疗选项之一。其窄谱抗菌谱和低耐药选择压力支持其作为首选药物的地位。指南建议的剂量（370 mg每日三次）与FDA批准的标签剂量有所不同。 对CRE的活性：在CRE分离株中，美西林对不同碳青霉烯酶类型的敏感性差异显著：KPC产生菌株中为0%（0/174），NDM-E中为71%（1,094株中），OXA-48-E中为84%（4,042株中），非碳青霉烯酶产生CRE中为70%（2,349株中）。因此，了解碳青霉烯酶类型对匹美西林的选用至关重要。2.3 硫培南 硫培南是一种新型硫青霉素类抗生素，其口服前体药物制剂硫培南乙酯与丙磺舒（probenecid）共同配制，于2024年10月获FDA批准。 体外活性：硫培南对超过95%的ESBL-E分离株具有活性。在ESBL-E uUTI患者中，5日硫培南疗程的治疗成功率（综合临床和微生物学应答）与3日环丙沙星疗程相似（56% [41/73] vs 47% [34/72]）。 指南推荐：硫培南为ESBL-E所致uUTI的首选治疗选项之一。最常见的不良事件为轻度腹泻。值得注意的是，丙磺舒可抑制肾小管分泌，可能增加其他药物（如甲氨蝶呤、哌拉西林、磺胺类药物）的血浆浓度。 cUTI数据：在一项随机试验中，硫培南治疗cUTI的复合终点（第21天临床和微生物学应答）未能达到非劣效性（68% [301/444] vs 74% [325/440]），但临床成功率相似（89% [397/444] vs 88% [389/440]），ESBL阳性感染患者的总体良好应答率也相似（72% [79/110] vs 68% [85/125]）。三、新型β-内酰胺/β-内酰胺酶抑制剂（BL/BLI）组合3.1 头孢吡肟-恩美唑巴坦 头孢吡肟-恩美唑巴坦是一种新型BL/BLI组合，于2024年获批。恩美唑巴坦是一种青霉烷砜类β-内酰胺酶抑制剂，对ESBL和部分A类碳青霉烯酶（KPC）具有抑制活性，但对B类金属β-内酰胺酶（MBL，如NDM）无抑制活性，对部分D类（OXA）酶活性有限。 指南推荐：头孢吡肟-恩美唑巴坦被列为ESBL-E所致肾盂肾炎/cUTI和尿路外感染的首选治疗方案之一。当耐药性、可及性或耐受性阻碍使用首选或替代药物时，也可用于ESBL-E uUTI。 剂量：2.5 g（2 g头孢吡肟 + 0.5 g恩美唑巴坦）IV，每8小时一次，输注2小时；肌酐清除率≥130 mL/min时调整为每8小时一次，输注4小时。3.2 氨曲南-阿维巴坦 氨曲南-阿维巴坦是2026版指南中最重要的新增药物之一。氨曲南对金属β-内酰胺酶（MBL）具有天然稳定性，但可被ESBL和AmpC酶水解；阿维巴坦可抑制丝氨酸β-内酰胺酶（包括ESBL、AmpC、KPC和OXA-48），保护氨曲南不被水解。这一组合对产MBL的肠杆菌目细菌（NDM-E）和嗜麦芽窄食单胞菌均具有独特活性。 指南推荐：NDM-E ：氨曲南-阿维巴坦被列为肾盂肾炎/cUTI和尿路外感染的首选治疗方案。对于CRE所致uUTI，氨曲南-阿维巴坦等静脉药物虽可能有效，但建议保留用于其他方案不可行的情况。S. maltophilia ：氨曲南-阿维巴坦新增为侵袭性感染的治疗选项。其机制在于L2头孢菌素酶可被阿维巴坦抑制，使氨曲南能够到达并结合PBP3靶点。监测数据显示超过90%的S. maltophilia分离株MIC ≤4/4 µg/mL。 剂量：负荷剂量2.67 g（2 g氨曲南 + 0.67 g阿维巴坦）IV一次，输注3小时；维持剂量2 g（1.5 g氨曲南 + 0.5 g阿维巴坦）IV，每6小时一次，输注3小时。3.3 静脉磷霉素（Fosfomycin IV） 静脉磷霉素于2025年10月获FDA批准，被纳入ESBL-E所致cUTI的替代治疗方案。其口服制剂（磷霉素氨丁三醇）仍为ESBL产酶大肠埃希菌uUTI的替代选项。 剂量：cUTI：6 g IV，每8小时一次，输注1小时；uUTI：3 g口服，单次剂量。四、AmpC-E风险分层体系 2026版IDSA指南在AmpC-E管理方面引入了重要的概念更新——弃用传统的SPACE/SPICE助记法，转而采用基于去阻遏（derepression）风险的分层体系。4.1 中风险组（Moderate Risk） 以下菌种被归类为临床显著诱导性AmpC产生的中等风险：阴沟肠杆菌复合群（Enterobacter cloacae complex）产气克雷伯菌（Klebsiella aerogenes，原产气肠杆菌）弗氏柠檬酸杆菌（Citrobacter freundii） 体外数据提示，Hafnia alvei可能具有相似的诱导性AmpC潜力，也可归入同一风险类别。 治疗建议：对于中风险菌种引起的侵袭性感染，IDSA推荐头孢吡肟或碳青霉烯类作为首选治疗，避免使用第三代头孢菌素（如头孢曲松、头孢他啶），因其与临床相关的AmpC去阻遏风险（5-40%）和治疗失败相关。4.2 低风险组（Low Risk） 以下菌种被归类为临床显著诱导性AmpC产生的低风险：黏质沙雷菌（Serratia marcescens）摩根摩根菌（Morganella morganii）普罗威登斯菌属（Providencia spp.）蜂房哈夫尼亚菌（Hafnia alvei）小肠结肠炎耶尔森菌（Yersinia enterocolitica） 低风险菌种的实际去阻遏风险估计<5%，且AmpC酶产量较中风险菌种低约10倍（Tebano等，2024）。 治疗建议：对于低风险菌种，第三代头孢菌素在特定情况下（如非重症感染、尿路感染）仍可考虑使用，但侵袭性感染仍建议谨慎（Tebano等，2024）。4.3 临床意义 这一分层体系的引入，旨在帮助临床医生更精准地评估不同AmpC产生菌种的治疗风险，避免对低风险菌种过度使用碳青霉烯类，同时对中风险菌种保持警惕。头孢吡肟因其对AmpC水解的稳定性且为弱诱导剂，被推荐为中风险AmpC-E感染的首选药物。五、CRAB治疗更新5.1 舒巴坦-度洛巴坦（SUL-DUR）的首选地位 2026版IDSA指南延续了2024年更新中的推荐，将舒巴坦-度洛巴坦（sulbactam-durlobactam, SUL-DUR）联合碳青霉烯类（亚胺培南或美罗培南）作为侵袭性CRAB感染的首选治疗。 关键证据：ATTACK试验（III期随机对照试验）纳入125例CRAB肺炎或血流感染患者，结果显示舒巴坦-度洛巴坦联合亚胺培南组的28天生存率高于多黏菌素联合亚胺培南组（81% [51/63] vs 68% [42/62]），临床治愈率也显著更优（62% [39/63] vs 40% [25/62]）。 作用机制：舒巴坦通过结合PBP1a/1b和PBP3发挥对鲍曼不动杆菌的直接杀菌活性；度洛巴坦作为二氮杂二环辛烷（DBO）类β-内酰胺酶抑制剂，可抑制A类、C类和D类（包括OXA型碳青霉烯酶）丝氨酸β-内酰胺酶。碳青霉烯类（亚胺培南优先结合PBP2）的加入通过互补PBP结合增强抗菌活性。5.2 桥接治疗方案 若舒巴坦-度洛巴坦无法立即获得，大剂量氨苄西林-舒巴坦（舒巴坦组分日总剂量9 g）联合至少一种其他活性药物（如头孢德罗（cefiderocol）、米诺环素或多黏菌素B）可作为临时桥接治疗，但仅限于舒巴坦-度洛巴坦启用前的过渡期。5.3 头孢德罗的定位 头孢德罗被列为侵袭性CRAB感染的替代方案，仅当耐药性排除舒巴坦-度洛巴坦使用或作为等待舒巴坦-度洛巴坦的桥接治疗时，且需联合第二种药物使用。CREDIBLE-CR试验中CRAB亚组的数据显示，头孢德罗组的28天死亡率为38%（16/42），高于最佳可用疗法组的18%（3/17），这一定位提供了依据。六、DTR-PA治疗更新 对于DTR铜绿假单胞菌引起的cUTI，IDSA（2026）推荐以下四种新型β-内酰胺类药物（按字母顺序排列，无优先顺序）为首选治疗： 头孢德罗 头孢他啶-阿维巴坦（Ceftazidime-Avibactam） 头孢洛生-他唑巴坦（Ceftolozane-Tazobactam） 亚胺培南-瑞来巴坦（Imipenem-Relebactam） 现有数据不足以优先推荐其中任何一种药物。然而，鉴于头孢德罗对NDM-E和非发酵革兰阴性菌具有独特活性，建议考虑将其保留用于其他AMR感染。 每日一次的阿米卡星或妥布霉素作为DTR-PA cUTI的替代治疗。 对于DTR-PA引起的尿路外感染，上述四种新型β-内酰胺类药物同样为首选，头孢德罗为替代方案。对于DTR-PA引起的呼吸道感染，不建议使用雾化抗生素。七、S. maltophilia治疗更新 2026版指南在嗜麦芽窄食单胞菌治疗方面的重要更新是纳入氨曲南-阿维巴坦作为推荐方案。 机制基础：S. maltophilia产生的L1金属β-内酰胺酶可水解所有β-内酰胺类（除氨曲南外），而L2头孢菌素酶可水解氨曲南。阿维巴坦可抑制L2头孢菌素酶，使氨曲南能够到达并结合PBP3靶点。 首选方案：头孢德罗仍为S. maltophilia侵袭性感染的首选治疗，监测数据显示其敏感性接近100%。 新推荐方案：氨曲南-阿维巴坦作为新的治疗选项被纳入。虽然CLSI和FDA尚未建立针对S. maltophilia的折点，但监测数据显示>90%的分离株MIC ≤4/4 µg/mL。八、CRE治疗更新 2026版指南保持了按碳青霉烯酶类型分层推荐CRE治疗的策略，同时新增了药物选项。8.1 CRE uUTI 对于CRE所致uUTI，首选治疗包括氨基糖苷类（单次剂量）、环丙沙星、左氧氟沙星、呋喃妥因或甲氧苄啶-磺胺甲噁唑，尽管CRE对这些药物的敏感性可能较低。 替代方案包括：多黏菌素、口服磷霉素（仅限大肠埃希菌）、吉泊达星或匹美西林。 多种静脉药物（如氨曲南-阿维巴坦、头孢德罗、头孢他啶-阿维巴坦、磷霉素[优先用于大肠埃希菌]、亚胺培南-瑞来巴坦、美罗培南-法硼巴坦）可能有效，但建议保留用于其他选项不可行的情况。8.2 CRE肾盂肾炎/cUTI和尿路外感染 按酶型分层的推荐如下： ← 左右滑动查看完整表格 → 酶型 首选方案 替代方案 KPC-E 头孢他啶-阿维巴坦、亚胺培南-瑞来巴坦、美罗培南-法硼巴坦 头孢德罗、头孢吡肟-恩美唑巴坦* NDM-E 头孢德罗、氨曲南-阿维巴坦 头孢他啶-阿维巴坦+氨曲南 OXA-48-E 头孢他啶-阿维巴坦 头孢德罗、亚胺培南-瑞来巴坦 头孢吡肟-恩美唑巴坦对KPC的活性有限，需结合药敏结果判断。九、一般管理建议更新9.1 经验性治疗考量 IDSA（2026）明确不提供经验性治疗的具体建议，但提出经验性选药应考虑以下因素：最可能的病原体、疾病严重程度、疑似感染源、患者个体因素、过去12个月内的微生物学数据及药敏结果、前3个月内的抗生素暴露史，以及当地流行病学和累积药敏数据。 指南特别强调区分感染与定植的重要性，并指出常用经验性方案通常对CRAB和S. maltophilia缺乏活性。9.2 疗程建议 IDSA（2026）不提供具体的治疗时长建议，但指出AMR病原体感染的疗程一般无需与敏感病原体感染者不同。若经验性方案对病原体无体外活性但患者已临床改善（如uUTI），通常无需更换方案或延长疗程。对于cUTI，若经验性治疗无效，应更换为敏感药物，疗程从启用有效治疗开始计算。9.3 静脉转口服（IV-to-Oral Transition） 推荐在满足以下条件时考虑转口服治疗： 1. 病原体对合适的口服药物敏感 2. 患者血流动力学稳定 3. 有可在感染部位达到足够浓度的口服药物 4. 预计胃肠道吸收充分十、更新总结与临床意义 2026版IDSA AMR指南更新的核心主题是"扩展治疗选择与精准化推荐"。三款新型口服药物的纳入，显著扩展了ESBL-E uUTI的口服治疗谱，有望减少碳青霉烯类药物的过度使用。氨曲南-阿维巴坦的纳入填补了NDM-E和S. maltophilia的治疗空白。AmpC-E风险分层体系的引入，标志着IDSA指南在抗生素管理方面向更精细化方向迈进。 总体而言，2026版更新反映了AMR治疗领域的快速进展——新型抗菌药物从临床试验进入临床实践，指南需要不断更新以跟上这一步伐。正如IDSA（2026）所述："AMR领域高度动态，本文档截至2026年3月1日，将定期更新。"参考文献 [1] IDSA. Infectious Diseases Society of America 2026 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2026. (www.idsociety.org/practice-guideline/amr-guidance/) [2] Tamma PD, Bonomo RA, Heil EL, et al. IDSA 2026 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. 2026. [3] Wagenlehner F, Perry CR, Hooton TM, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet. 2024;403(10428):741-755. [4] Watkins RR, Thapaliya D, Lemonovich TL, Bonomo RA. Gepotidacin: a novel, oral, 'first-in-class' triazaacenaphthylene antibiotic for the treatment of uncomplicated urinary tract infections and urogenital gonorrhoea. J Antimicrob Chemother. 2023;78(5):1137-1142. [5] Hackel MA, Karlowsky JA, Sahm DF, West JM, Scangarella-Oman NE. In vitro activity of gepotidacin against urinary tract infection isolates of Enterobacterales, Enterococcus faecalis, and Staphylococcus saprophyticus. Antimicrob Agents Chemother. 2025;69(6):e0029625. [6] Tebano G, Zaghi I, Cricca M, Cristini F. Antibiotic Treatment of Infections Caused by AmpC-Producing Enterobacterales. Pharmacy. 2024;12(5):142. [7] Tamma PD, Harris PNA, Mathers AJ, et al. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2024. [8] Kaye KS, Shorr AF, Wunderink RG, et al. ATTACK trial: Sulbactam-durlobactam versus colistin for the treatment of patients with infections caused by carbapenem-resistant Acinetobacter baumannii. Lancet Infect Dis. 2023;23(9):1072-1084. [9] Scangarella-Oman NE, Butler DL, Breton J, et al. Efficacy and in vitro activity of gepotidacin against bacterial uropathogens, including drug-resistant phenotypes, in females with uncomplicated urinary tract infections. Antimicrob Agents Chemother. 2025;69(10):e0164024.

WALTHAM, Mass.--(BUSINESS WIRE)--Innoviva Specialty Therapeutics (IST), a subsidiary of Innoviva, Inc. (NASDAQ: INVA), announced today that three of the company’s infectious disease therapies, XACDURO ® (sulbactam/durlobactam for injection), ZEVTERA ® (ceftobiprole medocaril sodium for injection), and NUZOLVENCE ® (zoliflodacin) are finalists for the 2026 Prix Galien USA Award in the Best Pharmaceutical Product category. This marks the third consecutive year an Innoviva Specialty Therapeutics product has been recognized by the renowned Galien Foundation. “This is the broadest slate of IST products to be designated as Prix Galien finalists, which is a testament to the clinical significance of the IST portfolio,” said Pavel Raifeld, Chief Executive Officer of Innoviva, Inc. “Each of these therapies addresses a distinct front in the fight against drug-resistant infections, and this nomination is further validation of our efforts to deliver life-saving medicines to patients.” The Prix Galien award is widely regarded as the industry’s equivalent of the Nobel Prize, recognizing groundbreaking advancements in the biopharmaceutical and medical technology industries that demonstrate the potential to significantly improve human health. The 2026 Award winners will be announced during a ceremony on October 29, 2026, in New York City. “As the public health crisis of antimicrobial resistance (AMR) further progresses, innovative therapeutics will continue to play an outsized role,” said David Altarac, MD, Chief Medical Officer at Innoviva Specialty Therapeutics. “To that end, considering that AMR is estimated to be associated with significant morbidity and millions of deaths worldwide each year, we’re privileged to be recognized for making notable strides in providing treatment for such difficult-to-treat infections.” ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); XACDURO, approved by the FDA in May 2023, remains the only antibiotic specifically approved for hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex, a pathogen the World Health Organization classifies as a critical-priority drug-resistant threat. ZEVTERA became in April 2024 the first cephalosporin approved by the FDA in nearly two decades for adults with Staphylococcus aureus bloodstream infections (bacteremia), including methicillin-resistant strains (MRSA), and is also indicated for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adult and pediatric patients. NUZOLVENCE, approved by the FDA in December 2025, is a first-in-class, single-dose oral therapy for drug-resistant urogenital gonorrhea, developed through IST’s collaboration with the Global Antibiotic Research and Development Partnership (GARDP), a not-for-profit organization. About The Prix Galien USA Award The Prix Galien was created in France in 1970 in honor of Galen, the father of medical science and modern pharmacology. The Galien Foundation oversees and directs activities in the U.S. for the Prix Galien Awards, which includes the biennial Prix Galien International Awards. To qualify for a Prix Galien USA Award, each candidate must have been an FDA-approved product for marketing within the last five years and demonstrate tremendous potential to improve human health. The nominating committee does not consider sales data when selecting award nominees; they consider science and health impact. About ZEVTERA ® (ceftobiprole medocaril sodium for injection) Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation cephalosporin antibiotic for intravenous administration, with rapid bactericidal activity against a wide range of Gram-positive bacteria, such as Staphylococcus aureus , including methicillin-resistant strains (MRSA), and Gram-negative bacteria. Outside the U.S., the brand is currently approved and marketed in several European countries and beyond as ZEVTERA ® and Mabelio ® for the treatment of adult patients with hospital-acquired bacterial pneumonia (HABP), excluding ventilator-associated bacterial pneumonia (VABP), and for the treatment of community-acquired bacterial pneumonia (CABP). Basilea has entered into license and distribution agreements covering more than 80 countries. INDICATIONS & USAGE Indications ZEVTERA ® (ceftobiprole medocaril sodium for injection), for intravenous use, is indicated for the treatment of: Adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. Adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following gram-positive and gram-negative microorganisms: Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, and Klebsiella pneumoniae . Adult and pediatric patients (3 months to less than 18 years) with community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following gram-positive and gram-negative microorganisms: Staphylococcus aureus (methicillin-susceptible isolates), Streptococcus pneumoniae, Haemophilus influenzae , Haemophilus parainfluenzae , Escherichia coli , and Klebsiella pneumoniae . Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZEVTERA and other antibacterial drugs, ZEVTERA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. IMPORTANT SAFETY INFORMATION Contraindications : ZEVTERA is contraindicated in patients with a known history of severe hypersensitivity to ZEVTERA, or to other members of the cephalosporin class. Warnings and Precautions: Increased mortality with unapproved use in ventilator-associated bacterial pneumonia (VABP) Patients: The safety and effectiveness of ZEVTERA for the treatment of VABP has not been established and the use of ZEVTERA for VABP is not approved. Serious hypersensitivity reactions, including anaphylaxis, were observed in ZEVTERA-treated patients in clinical trials. Serious and occasionally fatal hypersensitivity reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with ZEVTERA is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or other beta-lactam antibacterial drugs should be made. Maintain clinical supervision if this product is to be given to a penicillin- or other beta-lactam-allergic patient, because cross sensitivity among beta-lactam antibacterial agents has been established. Discontinue ZEVTERA if a hypersensitivity reaction occurs, and institute appropriate treatment. Seizures and other adverse central nervous system (CNS) reactions have been reported during treatment with ZEVTERA and other cephalosporins. If CNS adverse reactions, including seizures, occur, evaluate patients to determine whether ZEVTERA should be discontinued. Clostridioides difficile -associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including ZEVTERA, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, the risk/benefit of continuing treatment with ZEVTERA should be assessed. Adverse Reactions: SAB (adult patients): The most common adverse reactions occurring in ≥ 2% of adult patients were anemia, nausea, hypokalemia, vomiting, hepatic enzyme and bilirubin increased, diarrhea, blood creatinine increased, hypertension, leukopenia, pyrexia, abdominal pain, fungal infection, headache, and dyspnea. ABSSSI (adult patients): The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, diarrhea, headache, injection site reaction, hepatic enzyme increase, rash, vomiting, and dysgeusia. CABP (adult and pediatric patients 3 months to less than 18 years of age): Adult Patients: The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, hepatic enzyme increased, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, phlebitis, hypertension, and dizziness. Pediatric Patients: The most common adverse reactions occurring in ≥ 2% of pediatric patients were vomiting, headache, hepatic enzyme increased, diarrhea, infusion site reaction, phlebitis, and pyrexia. About XACDURO ® XACDURO ® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use, is a combination of sulbactam, a beta-lactam antibacterial, and durlobactam, a beta-lactamase inhibitor, approved in patients 18 years of age and older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex ( Acinetobacter ). XACDURO is not indicated for the treatment of HABP/VABP caused by pathogens other than susceptible isolates of Acinetobacter . Current US FDA approved XACDURO ® INDICATION & USAGE Indication XACDURO ® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. Limitations of Use XACDURO is not indicated for the treatment of HABP/VABP caused by pathogens other than susceptible isolates of Acinetobacter baumannii-calcoaceticus complex. Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of XACDURO and other antibacterial drugs, XACDURO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. IMPORTANT SAFETY INFORMATION Contraindications : XACDURO is contraindicated in patients with a history of known severe hypersensitivity to the components of XACDURO or other beta-lactam antibacterial drugs. Warnings and Precautions: Hypersensitivity was observed in patients treated with XACDURO in clinical trials. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before initiating therapy with XACDURO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta lactams, and other allergens. If an allergic reaction occurs, discontinue XACDURO. Clostridioides difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. If CDAD is suspected or confirmed, the risk/benefit of continuing treatment with XACDURO should be assessed. Prescribing XACDURO in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse Reactions: The most common adverse reactions reported in >10% of patients treated with XACDURO were liver test abnormalities (19%), diarrhea (17%), anemia (13%), and hypokalemia (12%). To report SUSPECTED ADVERSE REACTIONS, contact Innoviva Specialty Therapeutics, Inc. at 1-800-651-3861 or FDA at 1-800-FDA-1088 or . Before administering, please see the Full Prescribing Information for XACDURO . About NUZOLVENCE® (zoliflodacin) for oral suspension NUZOLVENCE is a first-in-class, single-dose, oral antibiotic FDA-approved for the treatment of uncomplicated urogenital gonorrhea, including strains resistant to current first-line therapies. NUZOLVENCE is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor indicated for the treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae in adults and pediatric patients 12 years of age and older, weighing at least 35 kg. The NUZOLVENCE mechanism of action is distinct from that of currently approved antibiotics and has demonstrated activity against drug-resistant Neisseria gonorrhoeae . Important Safety Information (ISI) Indication and Usage Indication NUZOLVENCE® is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor indicated for the treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae in adults and pediatric patients 12 years of age and older, weighing at least 35 kg. Usage to Reduce Development of Drug-Resistant Bacteria: To reduce the development of drug-resistant bacteria and maintain the effectiveness of NUZOLVENCE and other antibacterial drugs, NUZOLVENCE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. Contraindications Known history of hypersensitivity to NUZOLVENCE. Concomitant use with moderate or strong CYP3A4 inducers because this is predicted to result in decreased plasma concentrations of zoliflodacin and may reduce the NUZOLVENCE efficacy. Warnings and Precautions Embryo-Fetal Toxicity: Potential Risk for Pregnant Females Based on data from animal studies, NUZOLVENCE may cause fetal harm when administered to a pregnant female at clinically relevant doses. Avoid use during pregnancy. Advise pregnant females about the potential risk to the fetus with maternal exposure to NUZOLVENCE. Obtain a pregnancy test prior to initiation in persons of reproductive potential. Embryo-Fetal Toxicity: Potential Risk Related to Males with Female Partners of Reproductive Potential: Based on data from an animal toxicity study, the risk of early pregnancy loss may be increased in female partners of males treated with NUZOLVENCE. Advise males with female partners of reproductive potential to use effective contraception for at least 3 months after NUZOLVENCE administration. Testicular Toxicity and Risks to Male Fertility: Based on findings from animal studies, NUZOLVENCE may cause testicular toxicity and impair male fertility. An assessment of spermatogenesis has not been conducted in humans. Advise males that NUZOLVENCE may cause testicular toxicity and impair male fertility. Hypersensitivity Reactions: Hypersensitivity reactions, including rash and pruritus, have been reported in patients receiving NUZOLVENCE. Before therapy with NUZOLVENCE is instituted, carefully inquire about previous hypersensitivity reactions to NUZOLVENCE. If an allergic reaction to NUZOLVENCE occurs, discontinue NUZOLVENCE and institute appropriate supportive measures. Clostridioides difficile Infection (CDI): CDI has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. Development of Drug-Resistant Bacteria: Prescribing NUZOLVENCE in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse Reactions The most common adverse reactions (≥2%) are headache, dizziness, nausea, and diarrhea. Laboratory abnormalities (neutropenia, leukopenia) were also observed. Drug Interactions Concomitant use with moderate or strong CYP3A4 inducers is contraindicated. Use in Specific Populations Pregnancy: Based on findings from animal studies, NUZOLVENCE may cause fetal malformations or increased embryo-fetal loss when administered to a pregnant female. A postmarketing descriptive pregnancy safety study is available for NUZOLVENCE. If exposure occurs during pregnancy, pregnant females or their healthcare providers should report the pregnancy to Entasis Therapeutics at 1-800-651-3861. Lactation: There are no data on the presence of zoliflodacin in either human or animal milk, effects on the breastfed infant, or effects on milk production. If NUZOLVENCE is present in breast milk, intestinal flora alteration in the breastfed infant could occur. Females and Males of Reproductive Potential: Based on animal studies, NUZOLVENCE may cause fetal malformations when administered to a pregnant female at clinically relevant doses. Additionally, based on data from an animal study, the risk of early pregnancy loss may be increased in partners of males treated with NUZOLVENCE. Pregnancy Testing: Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with NUZOLVENCE. Contraception: Advise males with female partners of reproductive potential to use effective contraception for at least 3 months after their single-dose treatment of NUZOLVENCE. Infertility: Based on data from repeat-dose animal toxicity and fertility studies, NUZOLVENCE may cause testicular toxicity and impair male fertility. Pediatric Use: The safety and effectiveness of NUZOLVENCE in pediatric patients younger than 12 years of age or weighing less than 35 kg have not been established. Geriatric Use: Clinical studies of NUZOLVENCE did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Reporting Adverse Events You are encouraged to report negative side effects of prescription drugs to the FDA. To report SUSPECTED ADVERSE REACTIONS, please contact: Innoviva Specialty Therapeutics™ 1-800-651-3861 medinfo@istx.com U.S. Food and Drug Administration 1-800-FDA-1088 About Innoviva Specialty Therapeutics Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc., is focused on delivering innovative therapies in critical care and infectious disease. Innoviva Specialty Therapeutics’ products, through its affiliates, include GIAPREZA ® (angiotensin II), XERAVA ® (eravacycline), XACDURO ® (sulbactam for injection; durlobactam for injection), and NUZOLVENCE ® (zoliflodacin). Innoviva Specialty Therapeutics also markets ZEVTERA (ceftobiprole), an advanced-generation cephalosporin antibiotic, in the U.S. through an exclusive license from Basilea Pharmaceutica International Ltd, Allschwil. For more information about Innoviva Specialty Therapeutics, please visit . Forward Looking Statements This press release contains certain “forward-looking” statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, and future events. Innoviva intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. The words “anticipate”, “expect”, “goal”, “intend”, “objective”, “opportunity”, “plan”, “potential”, “target” and similar expressions are intended to identify such forward-looking statements. Such forward-looking statements involve substantial risks, uncertainties, and assumptions. These statements are based on the current estimates and assumptions of the management of Innoviva as of the date of this press release and are subject to known and unknown risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Innoviva to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: expected cost savings; lower than expected future royalty revenue from respiratory products partnered with GSK; the commercialization of RELVAR ® /BREO ® ELLIPTA ® , ANORO ® ELLIPTA ® , GIAPREZA ® , XERAVA ® , XACDURO ® , ZEVTERA ® and NUZOLVENCE ® in the jurisdictions in which these products have been approved; the strategies, plans and objectives of Innoviva (including Innoviva’s growth strategy and corporate development initiatives); the timing, manner, and amount of potential capital returns to shareholders; the development of the LYNX ® platform; the status and timing of clinical studies, data analysis and communication of results; the potential benefits and mechanisms of action of product candidates; expectations for product candidates through development and commercialization; the timing of regulatory approval of product candidates; and projections of revenue, expenses and other financial items; the timing, manner and amount of capital deployment, including potential capital returns to stockholders; and risks related to the Company’s growth strategy. Other risks affecting Innoviva are described under the headings “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” contained in Innoviva’s Annual Report on Form 10-K for the year ended December 31, 2025 and Quarterly Reports on Form 10-Q, which are on the Securities and Exchange Commission (“SEC”) and available on the SEC’s website at . Past performance is not necessarily indicative of future results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. The information in this press release is provided only as of the date hereof, and Innoviva assumes no obligation to update its forward looking statements on account of new information, future events or otherwise, except as required by law. ANORO ® , RELVAR ® and BREO ® are trademarks of the GSK group of companies. ZEVTERA is a trademark of Basilea Pharmaceutica International AG, Allschwil. Contacts Investor and Media Contact Irwin Tendler Head of Investor Relations Executive Director, Corporate Development investors.relations@inva.com