Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection

LaVergne, Stephanie M.; Hamilton, Theron; Biswas, Biswajit; Kumaraswamy, Monika; Schooley, Robert T.; Wooten, Darcy

doi:10.1093/ofid/ofy064

Cited by 184 publications

(127 citation statements)

References 9 publications

(9 reference statements)

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“…The patient improved with this therapy and ultimately had a favorable clinical outcome. Another patient infected with PDR A. baumannii was treated with bacteriophages by the same group (123). This was a 77-year-old man who underwent a craniectomy due to assault resulting in subdural and epidural empyema.…”

Section: New Therapeutic Optionsmentioning

confidence: 99%

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Isler¹,

Doi

Bonomo

et al. 2019

Antimicrob Agents Chemother

256

179

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Carbapenem-resistantAcinetobacter baumannii(CRAB) is a perilous nosocomial pathogen causing substantial morbidity and mortality. Current treatment options for CRAB are limited and suffer from pharmacokinetic limitations, such as high toxicity and low plasma levels. As a result, CRAB is declared as the top priority pathogen by the World Health Organization for the investment in new drugs. This urgent need for new therapies, in combination with faster FDA approval process, accelerated new drug development and placed several drug candidates in the pipeline. This article reviews available information about the new drugs and other therapeutic options focusing on agents in clinical or late-stage preclinical studies for the treatment of CRAB, and it evaluates their expected benefits and potential shortcomings.

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Section: New Therapeutic Optionsmentioning

confidence: 99%

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Isler¹,

Doi

Bonomo

et al. 2019

Antimicrob Agents Chemother

256

179

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“…However, other outcomes have also been observed [61,62,64]. The hope is for in vivo outcomes that avoid bacterial resistance, but in fact, resistant bacteria have been observed to ascend within patients [67]). So the hope then turns to learning how to choose phages to direct the outcome toward blocking bacterial resistance evolution.…”

Section: Resultsmentioning

confidence: 99%

Promises and pitfalls ofin vivoevolution to improve phage therapy

Bull

Levin

Molineux

2019

Preprint

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Background) Phage therapy is the use of bacterial viruses (phages) to treat bacterial 1 infections. Phages lack the broad host ranges of antibiotics, so individual phages are often used with 2 no prior history of use in treatment. Therapeutic phages are thus often chosen based on limited 3 criteria, sometimes merely an ability to plate on the pathogenic bacterium. It is possible that better 4 treatment outcomes might be obtained from an informed choice of phages. Here we consider whether 5 phages used to treat the bacterial infection in a patient might specifically evolve to improve treatment. 6 Phages recovered from the patient could then serve as a source of improved phages or cocktails for 7 use on subsequent patients. (Methods) With the aid of mathematical and computational models, we 8 explore this possibility for four phage properties expected to promote therapeutic success: in vivo 9 growth, phage decay rate, overcoming resistant bacteria, and enzyme activity to degrade protective 10 bacterial layers. (Results) Phage evolution only sometimes works in favor of treatment, and even in 11 those cases, intrinsic phage dynamics in the patient are usually not ideal. An informed use of phages 12is invariably superior to reliance on within-host evolution and dynamics, although the extent of this 13 benefit varies with the application. 14

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“…This has led to increased phage therapy exposure to the public and arguably increased clinical awareness regarding this alternative therapeutic. More recently another case study involving infection at a craniectomy site with a MDR- A. baumannii , applied a personalized phage cocktail intravenously in an attempt to improve patient outcomes (Lavergne et al, 2018 ). Unfortunately, the patient passed away after life support efforts were ceased following the family's request.…”

Section: The Challenge Of Multi-drug Resistant Bacteriamentioning

confidence: 99%

Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles

Furfaro

Payne

Chang

2018

Front. Cell. Infect. Microbiol.

249

179

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Increasing reports of antimicrobial resistance and limited new antibiotic discoveries and development have fuelled innovation in other research fields and led to a revitalization of bacteriophage (phage) studies in the Western world. Phage therapy mainly utilizes obligately lytic phages to kill their respective bacterial hosts, while leaving human cells intact and reducing the broader impact on commensal bacteria that often results from antibiotic use. Phage therapy is rapidly evolving and has resulted in cases of life-saving therapeutic use and multiple clinical trials. However, one of the biggest challenges this antibiotic alternative faces relates to regulations and policy surrounding clinical use and implementation beyond compassionate cases. This review discusses the multi-drug resistant Gram-negative pathogens of highest critical priority and summarizes the current state-of-the-art in phage therapy targeting these organisms. It also examines phage therapy in humans in general and the approaches different countries have taken to introduce it into clinical practice and policy. We aim to highlight the rapidly advancing field of phage therapy and the challenges that lie ahead as the world shifts away from complete reliance on antibiotics.

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Phage Therapy for a Multidrug-Resistant Acinetobacter baumannii Craniectomy Site Infection

Cited by 184 publications

References 9 publications

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Promises and pitfalls ofin vivoevolution to improve phage therapy

Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles

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