Rifabutin

April 21, 2026 2:11 pm EDT IDVYNSO is approved for adults with virologically suppressed HIV-1 with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine IDVYNSO is the first and only non-INSTI, tenofovir-free, once-daily, complete two-drug regimen to demonstrate non-inferior efficacy in a head-to-head Phase 3 trial versus three-drug regimen BIKTARVY®i (BIC/FTC/TAF) RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) approved IDVYNSO™, a new, two-drug single-tablet regimen of 100 mg doravirine and 0.25 mg islatravir, for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. IDVYNSO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers and lamivudine (3TC) or emtricitabine (FTC). Co-administration with these drugs may decrease the effectiveness of IDVYNSO. See additional selected safety information on the following pages. IDVYNSO (pronounced ihd-VIHN-soh) will be available in pharmacies after May 11. “Advances in HIV treatment mean more people living with HIV are living longer — a remarkable achievement,” said Carl Baloney, Jr., president and chief executive officer of AIDS United. “People aging with HIV face additional health challenges, including managing multiple chronic conditions and medications at the same time. It is essential that management of HIV considers these factors in addition to virologic suppression when choosing an HIV treatment regimen.” “IDVYNSO combines islatravir, a next-generation NRTI with multiple mechanisms of action, including translocation inhibition, with doravirine, an NNRTI with an established efficacy and safety profile. As the only two-drug, non-INSTI, tenofovir-free regimen, IDVYNSO expands therapeutic diversity beyond the currently available oral treatment options,” said Dr. Eliav Barr, senior vice president and chief medical officer, Merck Research Laboratories. “As the health needs of adults living with HIV change over time, IDVYNSO gives clinicians a new choice for HIV treatment. This approval marks an important new chapter in Merck’s long-standing commitment to research and discovery for people living with HIV.” IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, have been reported with doravirine-containing regimens. Drug Rash with Eosinophilia and Systemic Symptoms was reported with IDVYNSO. Concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance, or possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO. See additional selected safety information on the following pages. “IDVYNSO is the first non-INSTI, tenofovir-free, two-drug regimen to demonstrate non-inferior efficacy to standard oral antiretroviral regimens, including BIKTARVY. This makes IDVYNSO a potential alternative for people with virologically suppressed HIV who may need to switch their treatment,” said Dr. Amy Colson, director of research at Community Resource Initiative, Boston, Massachusetts. Phase 3 studies supporting approval of IDVYNSO The efficacy and safety of IDVYNSO is supported by Week 48 data from two randomized, active-controlled, non-inferiority trials [Trial 052 (NCT05630755) and Trial 051 (NCT05631093)] in virologically-suppressed (HIV-1 RNA less than 50 copies per mL) adults living with HIV. Participants must have been stably suppressed on their baseline regimen for at least 3 months prior to trial entry and had no history of treatment failure. Across the two trials, a total of 708 participants received once-daily IDVYNSO; of these, 81 (11%) participants were aged 65 years and older, including 10 (1%) aged 75 years and older. In the double-blind Trial 052, participants were switched from BIKTARVY [bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)] to IDVYNSO. A total of 513 participants were randomized (2:1) and were switched to once-daily IDVYNSO (n=342) or remained on BIC/FTC/TAF (n=171). At baseline, participants had a mean age of 48 years (range: 19 to 77), 21% of participants were female, 61% were White, 31% were Black/African American, and 6% were Asian. A total of 23% identified as Hispanic/Latino. In the open-label Trial 051, participants were switched from an oral ART (antiretroviral therapy) regimen to IDVYNSO. A total of 551 participants were randomized (2:1) and were switched to once-daily IDVYNSO (n=366) or remained on their baseline ART (bART) (n=185). Randomization was stratified by bART. At baseline, participants had a mean age of 50 years (range: 18 to 83), 40% of participants were female, 39% were White, 45% were Black/African American, and 5% were Asian. A total of 15% identified as Hispanic/Latino. At enrollment, 64% of the participants were receiving integrase strand transfer inhibitor (INSTI)-based regimens, 5% protease inhibitor (PI)-based regimens (including combinations with INSTI), and 30% were receiving other regimens. Efficacy profile of IDVYNSO IDVYNSO was non-inferior to BIC/FTC/TAF (in Trial 052) and bART (in Trial 051) as assessed by the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48. In the double-blind Trial 052, results for the primary endpoint (HIV-1 RNA ≥50 copies/mL) showed that 1% of participants who were switched to IDVYNSO (n=342) had a viral load of ≥50 copies/mL at Week 48, compared to 1% who continued on BIC/FTC/TAF (n=171; treatment difference 0.9%, 95% CI, -1.9%, 2.9%). At Week 48, results from the secondary endpoint showed that 92% of participants who switched to IDVYNSO maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 94% of participants who continued receiving BIC/FTC/TAF. In the open-label Trial 051, results for the primary endpoint (HIV-1 RNA ≥50 copies/mL) showed that 1% of participants who were switched to IDVYNSO (n=366) had a viral load of ≥50 copies/mL at Week 48, compared to 5% who continued on bART (n=185; treatment difference -3.6%, 95% CI, -7.8%, -0.8%). At Week 48, results from the secondary endpoint showed that 96% of participants who switched to IDVYNSO maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 92% of participants who continued on bART. In both trials, treatment outcomes between treatment groups were similar across subgroups by age, sex and race, and in Trial 051, also by bART regimens. In participants aged 65 years and older who received IDVYNSO in both trials, no overall differences in safety or effectiveness were observed between these participants and younger participants, but greater sensitivity of some older individuals cannot be ruled out. Safety and tolerability profile of IDVYNSO The safety profile of IDVYNSO was generally comparable to BIC/FTC/TAF in Trial 052 and to oral bART regimens in Trial 051. In Trial 052, by Week 48, 3% in the IDVYNSO group and 2% in the BIC/FTC/TAF group had adverse events leading to discontinuation of study medication. In Trial 051, by Week 48, 0.5% in the IDVYNSO group and 2% in the bART group had adverse events leading to discontinuation of study medication. The most common adverse reactions (all grades) reported in greater than or equal to 2% of participants in any treatment group in Trials 052 and 051 through Week 48 were as follows: In Trial 052 (IDVYNSO vs BIC/FTC/TAF, respectively): diarrhea (1% vs 1%), dizziness (1% vs 0%), fatigue (1% vs 1%), abdominal distention (1% vs 0%), headache (1% vs 0%), weight increase (less than 1% vs 0%). In Trial 051 (IDVYNSO vs bART, respectively): diarrhea (3% vs 0%), dizziness (2% vs 1%), fatigue (2% vs 1%), abdominal distention (2% vs 0%), headache (2% vs 1%), weight increase (2% vs 0%). Trial participants taking IDVYNSO had minimal change in weight from baseline. The mean change in weight from baseline at Week 48 was -0.03 kg in the IDVYNSO group vs. 0.28 kg in the BIC/FTC/TAF group in Trial 052 and 0.94 kg in the IDVYNSO group vs. -0.15 kg in the bART group in Trial 051. Four of the six participants with adverse reactions of weight increased switched from a bART regimen containing efavirenz and/or tenofovir disoproxil fumarate in Trial 051. The Merck Access Program for IDVYNSO Merck offers support to individuals who are prescribed IDVYNSO, including information about individual insurance coverage and out-of-pocket costs, co-pay assistance for eligible, commercially insured individuals, and how individuals may access IDVYNSO through The Merck Access Program. For additional information, healthcare providers and individuals can call 1-877-709-4455 or visit merckaccessprogram-IDVYNSO.com. About IDVYNSO IDVYNSO is a fixed-dose combination of two medicines, doravirine with islatravir. Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase. Islatravir is a potent, next-generation nucleoside analog reverse transcriptase inhibitor (NRTI) that blocks HIV-1 replication by multiple mechanisms including: inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and induction of structural changes in the viral DNA (delayed chain termination). Selected Safety Information for IDVYNSO Contraindications IDVYNSO is contraindicated when co-administered with: drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of IDVYNSO. lamivudine (3TC) or emtricitabine (FTC) as significant decreases in islatravir-triphosphate (ISL-TP) concentrations may occur, which may decrease the effectiveness of IDVYNSO. (See Drug Interactions) Warnings and Precautions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during postmarketing experience with doravirine-containing regimens. In addition, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) was reported with IDVYNSO in a clinical trial. Discontinue IDVYNSO, and other medications associated with these reactions, immediately if a painful rash with mucosal involvement, a progressive severe rash, or a rash with constitutional symptoms, eosinophilia, lymphadenopathy, or other organ involvement develops. Close clinical monitoring, and appropriate therapy should be initiated. The concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance and possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO. Consider the potential for drug interactions prior to and during IDVYNSO therapy, review concomitant medications during IDVYNSO therapy, and monitor for adverse reactions. (See Drug Interactions) Adverse Reactions The most common adverse reactions (incidence ≥ 2%, all grades in any treatment group) reported in virologically suppressed participants in the IDVYNSO treatment groups from 2 clinical trials, respectively, were: diarrhea (3% and 1%), dizziness (2% and 1%), fatigue (2% and 1%), abdominal distension (2% and 1%), headache (2% and 1%) and increased weight (2% and <1%). A single case of severe immune thrombocytopenia (platelet count nadir of 2 x10⁹/L) characterized by abrupt onset of subcutaneous hematoma, petechiae, and hematuria was reported in a participant 32 days after initiating IDVYNSO. The case resolved with discontinuation of IDVYNSO, in conjunction with treatments including corticosteroids and IVIG. Among all participants in Trials 052 and 051, there were no patterns of platelet decreases over time with IDVYNSO and no differences between treatment arms in mean change from baseline in platelet count. Drug Interactions IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Co-administration of IDVYNSO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce the efficacy of IDVYNSO. If IDVYNSO is co-administered with rifabutin, one tablet of doravirine should be taken approximately 12 hours after the dose of IDVYNSO. Co-administration of IDVYNSO with other moderate CYP3A inducers is not recommended. Co-administration of IDVYNSO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. Co-administration of IDVYNSO is not recommended with deoxycytidine kinase (dCK) substrates (e.g., nucleoside antimetabolites) as they may reduce the exposure of islatravir-triphosphate or with adenosine deaminase (ADA) inhibitors (e.g., pentostatin) as they may increase the exposure of islatravir. (see Contraindications) Use in Specific Populations Clinical trials in virologically suppressed participants who received IDVYNSO included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older. Overall differences in response have not been identified between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. IDVYNSO does not have activity against hepatitis B virus (HBV). Patients with HBV coinfection who switch to IDVYNSO from an antiretroviral regimen with activity against HBV, and patients on IDVYNSO who are newly diagnosed with HBV coinfection, should be closely monitored and specific anti-HBV therapy should be considered, as clinically appropriate. Merck’s Commitment to HIV For 40 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV. We are researching for real life and want to ensure people are not defined by HIV. Our work focuses on transformational innovations, collaborations with others in the global HIV community and access initiatives aimed at helping to end the HIV epidemic for everyone. About Merck’s HIV research Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in these two-drug regimens. Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1 [ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299)], and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development [MK-8591B-060 (NCT06891066) and MK-8591B-062 (NCT07266831)] as an oral once-weekly treatment. MK-8527 is the company’s investigational, novel, once-monthly oral candidate for pre-exposure prophylaxis (PrEP) for HIV-1. In collaboration with the Gates Foundation, the Phase 3 EXPrESSIVE-10 trial (MK-8527-010, NCT07071623) is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among women and adolescent girls in sub-Saharan Africa. The Phase 3 EXPrESSIVE-11 trial (MK-8527-011, NCT07044297) in 16 countries is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among people likely to be exposed to HIV-1. Both trials are now enrolling. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). Please see Prescribing Information for IDVYNSO™ (doravirine and islatravir) at https://www.merck.com/product/usa/pi_circulars/i/idvynso/idvynso_pi.pdf and Patient Information for IDVYNSO at https://www.merck.com/product/usa/pi_circulars/i/idvynso/idvynso_ppi.pdf. i IDVYNSO™ is a trademark of Merck & Co., Inc. BIKTARVY is a registered trademark of Gilead Sciences Ireland UC. Media Contacts: Melissa Moody (215) 407-3536 Deb Wambold (215) 779-2234 Investor Contacts: Damini Chokshi (732) 594-1577 Peter Dannenbaum (732) 594-1579

非结核分枝杆菌（Nontuberculous Mycobacteria, NTM）是指除结核分枝杆菌复合群和麻风分枝杆菌以外的其他分枝杆菌。迄今为止，已发现超过200种NTM菌种及亚种。NTM广泛存在于水、土壤等自然环境中，为条件致病菌。NTM病的治疗充满挑战，其特点包括：疗程漫长、药物不良反应多、耐药率高、治愈率不理想、复发率高。因此，临床医生必须遵循“菌种鉴定先行，药敏结果导向，多药联合，足量足疗程”的核心原则，制定个体化、精准化的治疗方案。 本文基于2020年ATS/ERS/ESCMID/IDSA临床实践指南、2020年中国非结核分枝杆菌病诊断与治疗指南、2026年中国HIV/AIDS患者合并NTM感染诊治专家共识等，对目前临床主要致病NTM菌种的治疗方案进行盘点，仅供临床参考。 一、NTM病治疗总则 1、治疗决策需综合评估：确诊NTM病后，并非所有患者均需立即治疗。临床医生应权衡利弊，综合评估患者的临床症状、影像学严重程度（尤其是空洞和痰涂片阳性）、病原菌的致病力和耐药性、患者的免疫状态、合并症、治疗意愿及耐受性。 2、菌种鉴定是前提：不同的NTM菌种对抗菌药物的敏感性差异巨大。因此，治疗前必须进行精确的菌种鉴定。分子生物学技术（如PCR、质谱、高通量测序）是快速、准确鉴定菌种的首选方法。 3、药敏试验是关键：尽管体外药敏与临床疗效的相关性尚不完全明确，但对于已经明确的关联（如大环内酯类和阿米卡星对MAC和脓肿分枝杆菌、利福平对堪萨斯分枝杆菌），药敏试验结果是制定有效化疗方案的基石。 4、联合用药与足疗程：NTM治疗需采用多药联合方案，以增强疗效、防止耐药产生。疗程通常较长，一般要求在痰菌阴转后持续治疗至少12个月，对于难治性MAC和脓肿分枝杆菌复合群（MABSC）等难治菌种，结合个体情况，疗程通常需延长至18-24个月。 5、治疗管理与监测：治疗期间必须密切监测药物不良反应（如肝肾功能、血常规、听力、视力、心电图等），并及时处理，推荐进行治疗药物监测（TDM）。同时，应关注患者的依从性、营养状况和心理支持。 6、HIV合并感染的特殊性：对于HIV/AIDS患者合并NTM感染，需高度关注抗NTM药物与抗逆转录病毒药物之间的相互作用（DDI），此时优先选择相互作用相对小的药物（如利福布汀），并警惕免疫重建炎性综合征（IRIS）。 7、避免过度治疗：仅确诊为NTM病的患者需要治疗；对于无症状、无影像学改变的NTM定植或感染，建议观察随访。 二、主要致病NTM菌种的治疗方案 （一）、鸟分枝杆菌复合群（MAC） MAC是全球最常见的NTM肺病病原体，包括鸟分枝杆菌和胞内分枝杆菌等。其治疗方案以大环内酯类药物为核心。 1、大环内酯类敏感的MAC肺病 方案：大环内酯类+ 利福霉素类 + 乙胺丁醇的三药联合方案。 给药频次与疗程： 非空洞型结节/支气管扩张型：推荐每周3次的间歇给药方案。 阿奇霉素500-600mg/次，或克拉霉素 1000mg/次； 乙胺丁醇25mg/kg/次； 利福平600mg/次。 空洞型或严重/进展性支气管扩张型：推荐每日给药方案。 阿奇霉素250-500mg/d，或克拉霉素 500-1000mg/d（体重<50kg时用500mg/d）； 利福平450-600mg/d（体重<50kg时用450mg/d）； 乙胺丁醇15 mg/kg/d。 初始强化治疗：对于空洞型、病变广泛或大环内酯类耐药的MAC肺病，建议在治疗开始的前2-3个月联合阿米卡星（15mg/kg/d，静脉滴注或肌内注射）进行强化治疗。 疗程：痰培养阴转后至少12个月。 2、难治性或治疗失败的MAC肺病 对于规范治疗≥6个月痰培养仍未阴转的患者，视为治疗失败。此时应在评估依从性、药物吸收、耐药性后，调整方案。 处置策略：加用阿米卡星脂质体吸入混悬液（ALIS）。 方案：在原有口服方案（阿奇霉素/克拉霉素 + 利福布汀/利福平 + 乙胺丁醇）基础上，加用ALIS 590mg/次（基于CONVERT研究），每日1次，雾化吸入。 临床用药评价公众号：ALIS可将高浓度阿米卡星直接递送至肺部巨噬细胞内，提高局部药物浓度，减少全身暴露和毒性。是经权威指南（ATS/IDSA）强推荐用于MAC肺病治疗失败患者的方案。 疗程：对于难治性、大环内酯类耐药或伴有广泛空洞的MAC肺病，尽管标准疗程为痰菌阴转后12个月，但在临床实践中，基于患者治疗反应和耐受性，巩固治疗期常需延长至18-24个月，以降低复发风险。对于脓肿分枝杆菌复合群（MABC）肺病，总疗程通常需要18-24个月或更长。所有疗程决策均应遵循个体化原则，并在多学科团队讨论下进行。 3、大环内酯类耐药的MAC肺病 此类患者治疗极为困难，预后差。需选用二线或替代药物组合。 推荐方案：利福布汀（300mg/d）或利福平（450-600mg/d）+ 乙胺丁醇（15mg/kg/d）+ 异烟肼（300 mg/d）+ 莫西沙星（400mg/d）或环丙沙星（1000 mg/d，作为备选），口服。治疗开始前3个月应用阿米卡星强化。 替代/添加药物：可考虑氯法齐明（100-200mg/d）。研究显示，MIC值≤0.25mg/L的患者获益更显著。 （二）、脓肿分枝杆菌复合群（MABC） MABC是快速生长型NTM中最重要、治疗最棘手的病原体，包括脓肿亚种、马赛亚种和博莱亚种。其对多种一线抗结核药物天然耐药。 亚种鉴定：区分亚种对判断大环内酯类诱导耐药至关重要。基于大环内酯类药敏试验（必须包括14天孵育）和/或erm(41)基因检测，评估是否存在诱导性耐药。 1、大环内酯类敏感或诱导耐药的MABC肺病 治疗分为初始阶段（静脉强化）和延续阶段（口服/雾化巩固）。 初始阶段（至少4周，通常2-3个月）：采用≥3种有效药物（注射剂+口服）的方案。 阿米卡星：15mg/kg/d，每日1次，静脉滴注； 替加环素：首剂100mg，之后50mg/次，每日2次，静脉滴注； 亚胺培南/西司他丁：1g/次，每日2次，静脉滴注。（亚胺培南可加量至1g q6h以增强疗效）； 头孢西丁：200mg/kg/d，分3次给药，静脉滴注，最大量不超过12g/d。（可作为替代或联合用药）； 大环内酯类（口服）：克拉霉素500mg/次，每日2次；或阿奇霉素250-500mg/d。临床用药评价公众号：对于诱导耐药菌株，大环内酯类不视为有效抗菌药物，但其免疫调节作用仍可能使部分患者获益。 延续阶段：转为口服/雾化方案，持续至痰培养阴转后至少12个月，通常需18-24个月。 雾化阿米卡星：400mg/次，每日2次，雾化吸入； 口服大环内酯类：克拉霉素500mg/次，每日2次；或阿奇霉素250-500mg/d。 以上方案可联合以下口服药物（根据药敏和耐受性选择1-3种）： 利奈唑胺：600mg/d，口服。（注意骨髓抑制、周围神经炎、视神经炎）； 米诺环素：100mg/次，每日2次，口服。（注意光敏反应、头晕）； 氯法齐明：100-200mg/d，口服。（注意皮肤黏膜着色、QTc间期延长）； 莫西沙星：400mg/d，口服。（对MABC活性弱，仅作备选）。 2、大环内酯类高度耐药（组成型耐药，主要由 23S rRNA基因发生突变导致）的MABC肺病 初始阶段方案同上，但不包含大环内酯类药物。延续阶段选择非大环内酯类口服药物联合治疗。 3、新型药物与未来方向 第三代四环素类：奥马环素、依拉环素，体外研究显示对MABC有强大活性，临床个案报道及小样本研究显示良好的治疗前景。 双β-内酰胺类：头孢托罗（Ceftobiprole） + 亚胺培南，是未来有潜力的组合。 吸入制剂：吸入替加环素、吸入氯法齐明等正在研究中。 贝达喹啉、德拉马尼、噬菌体疗法：目前证据不足，不被常规推荐，可考虑用于临床试验或作为最后手段。 （三）、堪萨斯分枝杆菌（M. kansasii） 堪萨斯分枝杆菌是光产色菌，致病性强，但治疗方案成熟，疗效和预后是NTM肺病中最好的，治愈率超过80%。利福平是核心药物，几乎所有菌株对其敏感。如出现利福平耐药，治疗难度显著增加。 1、利福平敏感的堪萨斯分枝杆菌肺病 推荐方案：利福平+ 乙胺丁醇 + 异烟肼或大环内酯类的三药联合方案。 利福平：450-600mg/d（体重<50kg时用450mg/d），每日1次，口服。 乙胺丁醇：15-25mg/kg/d，口服。（监测视神经毒性） 异烟肼：300mg/d，口服。（注意肝毒性、周围神经炎，可同服维生素B6预防） 阿奇霉素：250-500mg/d，口服。（或克拉霉素500-1000mg/d） 给药频次与疗程： 非空洞型：可选择每日给药或每周3次间歇给药。 空洞型：必须每日给药。 疗程：至少12个月。 2、利福平耐药的堪萨斯分枝杆菌肺病 此类情况少见但治疗棘手。推荐使用二线方案。 推荐方案：克拉霉素（500-1000mg/d）或阿奇霉素（250-500mg/d）+ 莫西沙星（400mg/d）+ 氯法齐明（100-200mg/d）或利奈唑胺（600 mg/d）+ 乙胺丁醇（15mg/kg/d）。 疗程：痰培养阴转后至少12个月。 （四）、蟾蜍分枝杆菌（M. xenopi） 治疗难度介于MAC和MABC之间，死亡率相对较高，治疗应更积极。 推荐方案：至少三药联合的每日给药方案。利福平+ 乙胺丁醇 + 莫西沙星或大环内酯类。 利福平：450-600mg/d（体重<50kg时用450mg/d）。 乙胺丁醇：15mg/kg/d。 莫西沙星：400mg/d。 阿奇霉素：250-500mg/d（或克拉霉素500-1000mg/d）。 强化治疗：对于空洞型或严重/进展性支气管扩张患者，建议在治疗开始前3个月联合阿米卡星（15mg/kg/d，静脉滴注）。 总疗程：痰培养阴转后至少12个月。 （五）其他少见或特定部位NTM感染的治疗 1、皮肤软组织NTM病 多见于外伤、手术或医疗美容术后感染，常见菌种为海分枝杆菌、脓肿分枝杆菌、偶发分枝杆菌、龟分枝杆菌等。 海分枝杆菌病：推荐克拉霉素（1000mg/d）联合利福平（600mg/d）或乙胺丁醇（1000mg/d）治疗。其他可选药物包括莫西沙星、多西环素、米诺环素、复方新诺明。总疗程一般为4-6个月，应在皮损完全消退后继续治疗1-2个月。 快速生长型分枝杆菌病（脓肿、偶发、龟分枝杆菌）：初始阶段可参考MABC肺病的初始静脉方案，疗程至少4个月，骨病患者至少6个月。手术清创或异物取出对于控制局部感染至关重要。 2、HIV/AIDS合并播散性MAC病 治疗：与MAC肺病方案类似，但需优先选择利福布汀以减少与抗病毒药物的相互作用。 方案：克拉霉素（500-1000mg/d）+ 利福布汀（300mg/d）+ 乙胺丁醇（15mg/kg/d）。疗程需持续至免疫功能恢复（CD4+T细胞>100个/μL并维持≥6个月）后至少12个月。 一级预防：对于CD4+T细胞计数<50个/μL的患者，推荐使用阿奇霉素1200 mg/周或克拉霉素1000 mg/d或利福布汀300mg/d进行预防。 3、瘰疬分枝杆菌病 推荐方案：氯法齐明（100-200mg/d）+ 克拉霉素（500-1000mg/d）/阿奇霉素（250-500mg/d）+ 环丙沙星（1000mg/d）+ 乙胺丁醇（15mg/kg/d）。 4、偶发分枝杆菌病 对多种药物敏感。肺病或播散性病变可参考MAC方案或选用以氟喹诺酮类为核心的方案，如环丙沙星联合克拉霉素等。 三、外科治疗与难治性NTM病管理 1、外科治疗的地位 手术是抗NTM药物治疗的重要辅助手段，但不作为首选。需经多学科专家团队（MDT）严格评估后实施。 适应证： 局限于单侧肺叶/肺段的病灶，经规范内科治疗（≥6个月）失败。 大环内酯类耐药或MABC等高度耐药菌感染。 出现难以控制的大咯血等严重并发症。 围手术期管理：术前需优化患者营养状况和心肺功能。术后必须继续抗NTM治疗，直至痰培养阴转后至少12个月。 2、难治性NTM-PD的管理策略（2026 ERS共识） 对于标准方案治疗失败（定义为规范治疗6个月后痰培养仍未阴转）的患者，应启动以患者为中心的共享决策模式，将患者分为两大路径： 强化治疗路径（目标：追求治愈）：适用于年轻、基础病少、病灶局限、可耐受强化方案的患者。策略包括：加用ALIS（针对MAC）、启用或优化静脉强化方案（针对MABC）、评估手术可能、参加新药临床试验。 降级治疗路径（目标：控制症状、改善生活质量）：适用于高龄、多重合并症、药物不耐受、反复治疗失败的患者。策略包括： 间歇给药（如3药改为每周3次）。 简化方案（如MAC简化为阿奇霉素+乙胺丁醇两药）。 暂停抗NTM治疗，以最佳支持治疗（呼吸康复、气道廓清、营养支持）为主，密切随访观察。 间断性短期静脉抗生素疗程以控制急性加重。 临床用药评价公众号：所有难治病例均建议转诊至NTM专科中心或多学科团队进行管理。 结 语 NTM病的治疗已进入精准化、个体化时代，不同指南给出的方案和疗程略有差异。临床医生应熟练掌握不同菌种的治疗方案、药物特性及注意事项，以患者为中心，权衡利弊，做出最佳临床决策。同时，应密切关注新药研发进展，积极参与多中心临床研究，共同推动NTM病诊疗水平的不断提升。 参考文献： [1] Daley CL, Iaccarino JM, Lange C, et al. 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