新型方法应对囊性纤维化中的多重耐药感染。

Novel Approaches to Multidrug-Resistant Infections in Cystic Fibrosis.

机构信息

Department of Pediatrics, Section Infectious Diseases and Global Health, Yale University School of Medicine, PO Box 208064, 333 Cedar Street, New Haven, CT 06520-8064, USA.

Department of Internal Medicine, Section Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, PO Box 208057, 300 Cedar Street TAC-441 South, New Haven, CT 06520-8057, USA; Adult Cystic Fibrosis Program; Yale University Center for Phage Biology & Therapy.

出版信息

Clin Chest Med. 2022 Dec;43(4):667-676. doi: 10.1016/j.ccm.2022.06.008.

DOI:10.1016/j.ccm.2022.06.008

PMID:36344073

Abstract

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.

摘要

囊性纤维化 (CF) 患者常发生呼吸道感染，病原体为耐多药的致病微生物（MDROs），如耐甲氧西林金黄色葡萄球菌和多种革兰氏阴性菌，包括铜绿假单胞菌、伯克霍尔德菌属、嗜麦芽寡养单胞菌、木糖氧化无色杆菌和非结核分枝杆菌（NTM）。尽管引入了新的治疗方法来解决潜在的囊性纤维化跨膜电导调节因子（CFTR）功能障碍，但 MDRO 感染仍然是一个问题，仍需要新型抗菌干预措施。治疗方法包括通过根据 CF 患者药代动力学/药效学的差异调整剂量来提高现有药物的疗效，开发吸入制剂以减少全身不良事件，以及使用新型β-内酰胺/β-内酰胺酶联合用药。替代创新的治疗方法包括使用镓和噬菌体来治疗 MDRO 肺部感染，包括那些具有极端抗生素耐药性的感染。然而，需要更多的临床试验来确定这些不同策略的最佳剂量和疗效，并确定最有可能从这些新治疗选择中获益的 CF 患者。