Early clinical experience of bacteriophage therapy in 3 lung transplant recipients

被引:205
作者
Aslam, Saima [1 ]
Courtwright, Andrew M. [2 ]
Koval, Christine [3 ]
Lehman, Susan M. [4 ]
Morales, Sandra [4 ]
Furr, Carrie-Lynn Langlais [4 ]
Rosas, Francisco [4 ]
Brownstein, Michael J. [5 ]
Fackler, Joseph R. [5 ]
Sisson, Brittany M. [5 ]
Biswas, Biswajit [6 ]
Henry, Matthew [6 ]
Luu, Truong [6 ]
Bivens, Brittany N. [6 ]
Hamilton, Theron [6 ]
Duplessis, Christopher [6 ]
Logan, Cathy [1 ]
Law, Nancy [1 ]
Yung, Gordon [7 ]
Turowski, Jason [8 ]
Anesi, Judith [9 ]
Strathdee, Steffanie A. [1 ]
Schooley, Robert T. [1 ]
机构
[1] Univ Calif San Diego, Div Infect Dis & Global Publ Hlth, La Jolla, CA 92093 USA
[2] Univ Penn, Dept Pulm & Crit Care Med, Philadelphia, PA 19104 USA
[3] Cleveland Clin Fdn, Dept Infect Dis, 9500 Euclid Ave, Cleveland, OH 44195 USA
[4] AmpliPhi Biosci, San Diego, CA USA
[5] Adapt Phage Therapeut, Gaithersburg, MD USA
[6] Naval Med Res Ctr, Biol Def Res Directorate, Ft Detrick, MD USA
[7] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, La Jolla, CA 92093 USA
[8] Cleveland Clin Fdn, Dept Pulm Med, 9500 Euclid Ave, Cleveland, OH 44195 USA
[9] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
antibiotic drug resistance; antibiotic; antibacterial; clinical research; practice; infection and infectious agents - bacterial; infectious disease; lung disease; infectious; lung transplantation; pulmonology; translational research; science; PSEUDOMONAS-AERUGINOSA; PHAGE THERAPY;
D O I
10.1111/ajt.15503
中图分类号
R61 [外科手术学];
学科分类号
摘要
Bacteriophage therapy (BT) uses bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in 3 lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n = 2) and Burkholderia dolosa (n = 1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described, as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient died. No BT-related adverse events were identified in the 3 cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections.
引用
收藏
页码:2631 / 2639
页数:9
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