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

Author:

Schooley Robert T.1,Biswas Biswajit23,Gill Jason J.45,Hernandez-Morales Adriana6,Lancaster Jacob5,Lessor Lauren5,Barr Jeremy J.78,Reed Sharon L.19,Rohwer Forest7,Benler Sean7,Segall Anca M.7,Taplitz Randy1,Smith Davey M.1,Kerr Kim1,Kumaraswamy Monika1,Nizet Victor1011,Lin Leo10,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.14,Regeimbal James M.2,Estrella Luis A.2,Wolfe David M.2,Henry Matthew S.23,Quinones Javier23,Salka Scott15,Bishop-Lilly Kimberly A.23,Young Ry56,Hamilton Theron2

Affiliation:

1. Department of Medicine, University of California, San Diego, La Jolla, California, USA

2. Biological Defense Research Directorate, Naval Medical Research Center, Frederick, Maryland, USA

3. Henry M. Jackson Foundation, Bethesda, Maryland, USA

4. Department of Animal Science, Texas A&M University, College Station, Texas, USA

5. Center for Phage Technology, Texas A&M AgriLife Research and Texas A&M University, College Station, Texas, USA

6. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA

7. Department of Biology, San Diego State University, San Diego, California, USA

8. Monash University, School of Biological Sciences, Melbourne, Australia

9. Department of Pathology, University of California, San Diego, La Jolla, California, USA

10. Department of Pediatrics, University of California, San Diego, La Jolla, California, USA

11. Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA

12. National Biodefense Analysis and Countermeasures Center, Frederick, Maryland, USA

13. Department of Radiology, University of California, San Diego, La Jolla, California, USA

14. Advanced Surgical Imaging Program, Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, Maryland, USA

15. AmpliPhi Biosciences, San Diego, California, USA

Abstract

ABSTRACT 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. baumannii 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. baumannii 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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference31 articles.

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