Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection

被引:874
作者
Schooley, Robert T. [1 ]
Biswas, Biswajit [2 ,3 ]
Gill, Jason J. [4 ,5 ,6 ]
Hernandez-Morales, Adriana [7 ]
Lancaster, Jacob [5 ,6 ]
Lessor, Lauren [5 ,6 ]
Barr, Jeremy J. [8 ,16 ]
Reed, Sharon L. [1 ,9 ]
Rohwer, Forest [8 ]
Benler, Sean [8 ]
Segall, Anca M. [8 ]
Taplitz, Randy [1 ]
Smith, Davey M. [1 ]
Kerr, Kim [1 ]
Kumaraswamy, Monika [1 ]
Nizet, Victor [10 ,11 ]
Lin, Leo [10 ]
McCauley, Melanie D. [1 ]
Strathdee, Steffanie A. [1 ]
Benson, Constance A. [1 ]
Pope, Robert K. [12 ]
Leroux, Brian M. [12 ]
Picel, Andrew C. [13 ]
Mateczun, Alfred J. [2 ]
Cilwa, Katherine E. [15 ]
Regeimbal, James M. [2 ]
Estrella, Luis A. [2 ]
Wolfe, David M. [2 ]
Henry, Matthew S. [2 ,3 ]
Quinones, Javier [2 ,3 ]
Salka, Scott [14 ]
Bishop-Lilly, Kimberly A. [2 ,3 ]
Young, Ry [5 ,6 ,7 ]
Hamilton, Theron [2 ]
机构
[1] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA
[2] Naval Med Res Ctr, Biol Def Res Directorate, Frederick, MD USA
[3] Henry M Jackson Fdn, Bethesda, MD USA
[4] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA
[5] Texas A&M AgriLife Res, Ctr Phage Technol, College Stn, TX USA
[6] Texas A&M Univ, College Stn, TX USA
[7] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
[8] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA
[9] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA
[10] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA
[11] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA
[12] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD USA
[13] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA
[14] AmpliPhi Biosci, San Diego, CA USA
[15] Naval Med Res Ctr, Dept Regenerat Med, Adv Surg Imaging Program, Silver Spring, MD USA
[16] Monash Univ, Sch Biol Sci, Melbourne, Vic, Australia
关键词
Acinetobacter; bacteriophage therapy; multidrug resistance; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; ANTIBIOTIC SYNERGISM; PHAGE THERAPY; RESCUES MICE; BANGLADESH; DISCOVERY; DIARRHEA; CHILDREN; TRIAL;
D O I
10.1128/AAC.00954-17
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii. We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. bournannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baurnannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
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页数:14
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