Boucher Helen W, Ambrose Paul G, Chambers H F, Ebright Richard H, Jezek Amanda, Murray Barbara E, Newland Jason G, Ostrowsky Belinda, Rex John H
Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Tufts University School of Medicine.
Institute for Clinical Pharmacodynamics, Schenectady.
J Infect Dis. 2017 Jul 15;216(2):228-236. doi: 10.1093/infdis/jix211.
Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant gram-negative bacilli continue to cause unacceptable morbidity and mortality rates. Antibacterial agents have been historically studied in noninferiority clinical trials that focus on a single site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, toward this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific clinical trials and ultimately approval of critically needed new antibacterial agents.
尽管抗菌药物研发取得了进展，但对于开发抗菌剂以治疗耐药菌感染的人群而言，仍迫切需要新的可行途径。耐革兰氏阴性杆菌引起的感染继续导致不可接受的发病率和死亡率。抗菌剂历来是在非劣效性临床试验中进行研究的，这些试验侧重于单一感染部位（如复杂性尿路感染、腹腔内感染），然而，对于耐药菌引起的感染研究，这些设计可能并非最佳，而且往往不可行。在过去几年中，多个利益相关方致力于就前进道路达成共识，目标是促进抗菌药物研发的及时开展。在此，我们倡导一种新颖且务实的方法，并为此提出抗菌剂的可行试验设计，这些设计能够开展窄谱、针对特定病原体的临床试验，并最终批准急需的新型抗菌剂。
