Center for Innovative Phage Applications and Therapeutics

Last updated
Center for Innovative Phage Applications and Therapeutics (IPATH)
FoundedJune 21, 2018;4 years ago (2018-06-21) [1]
Focus Phage therapy
Location
Co-Director
Steffanie A. Strathdee, Ph.D. [2]
Co-Director
Robert T. Schooley M.D. [2]
Website ipath.ucsd.edu

The Center for Innovative Phage Applications and Therapeutics (IPATH) is the first phage therapy center in North America, founded in the UC San Diego School of Medicine in June 2018, with seed funding from UC San Diego Chancellor Pradeep Khosla. [3] The center was founded by Steffanie A. Strathdee and Robert "Chip" Schooley, both professors at UC San Diego School of Medicine. The center currently treats patients with life-threatening multi-drug resistant infections with phage therapy, on a case-by-case basis, through the Food and Drug Administration's (FDA's) compassionate use program. IPATH aims to initiate phase I/II phage therapy clinical trials, focusing on patients with cystic fibrosis and infections related to implantable hardware, such as pacemakers and prosthetic joints. [4] The first planned clinical trial is set to look at otherwise healthy cystic fibrosis patients that are shedding Pseudomonas aeruginosa .

Contents

Phage therapy

Phage therapy is the method by which bacteriophages (viruses which infect bacteria) are used to treat bacterial infections or reduce bacterial populations. Phage therapy has gained recent attention in the United States as an alternative to standard antibiotic therapy. [5] [6] [7] It has been in practice for just over 100 years in countries such as Russia and Georgia, but due to the recent clinical attention of antibiotic resistance, Western countries have slowly been integrating phage therapy into their medicinal arsenal. Currently, in the United States, phages are used for treating bacterial infections only when patients have multi-drug resistant (MDR) life-threatening infections, or when patients are immunocompromised and antibiotic therapy is not a viable option. To date, the majority of phage therapy in the United States has been administered intravenously (IV), by utilizing the Emergency Investigational New Drug (eIND) process which is regulated by the FDA.

Phage therapy at UC San Diego School of Medicine

Tom Patterson was the first patient to be treated with phage therapy at a UC San Diego hospital in March 2016. Patterson had a systemic Acinetobacter baumannii infection that manifested while he was on vacation with his wife, Steffanie Strathdee, in Egypt. Strathdee advocated and connected with phage researchers around the United States and secured the help of friend and fellow UC San Diego professor, Robert "Chip" Schooley, who was head of the Division of Infectious Disease at the UC San Diego School of Medicine at the time. Researchers from Texas A&M University, Adaptive Phage Therapeutics, the US Navy, and San Diego State University, worked to source and purify phage that could be used to treat Patterson's infection intravenously. The FDA gave their approval for Patterson's phage therapy, through the eIND mechanism. After eight weeks of phage therapy, in conjunction with 12 weeks of antibiotics, no evidence of Acinetobacter baumannii was found in Patterson's body following June 6, 2016. [5] [8]

After positive media attention from Patterson's phage therapy, [9] [10] [11] Schooley and Strathdee began to receive phage therapy requests from around the globe. They were involved in the treatment of five other phage therapy patients at UC San Diego School of Medicine and consulted on numerous cases throughout the United States and Europe, before officially establishing IPATH in June 2018.

Future of IPATH

Since establishing in 2018, IPATH has been led by Co-directors Strathdee and Schooley, and have set out to lay the foundation for an academic center on the forefront of translational phage therapy research. Schooley and Strathdee bring with them numerous years of research experience and experience in designing clinical trials, which they are utilizing to initiate the first phage therapy clinical trials at UC San Diego School of Medicine. IPATH clinical trials will be housed at UC San Diego's AntiViral Research Center, which has been conducting clinical trials since 1986. [12] Initial clinical trials are planned to focus on multi-drug resistant infections associated with cystic fibrosis and implantable devices.

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Bacteriophage</span> Virus that infects and replicates within bacteria

A bacteriophage, also known informally as a phage, is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν, meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.

<i>Acinetobacter</i> Genus of bacteria

Acinetobacter is a genus of gram-negative bacteria belonging to the wider class of Gammaproteobacteria. Acinetobacter species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification.

<span class="mw-page-title-main">Phage therapy</span> Therapeutic use of bacteriophages to treat bacterial infections

Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections. This therapeutic approach emerged at the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the second world war. Bacteriophages, known as phages, are a form of virus that attach to bacterial cells and inject their genome into the cell. The bacteria's production of the viral genome interferes with its ability to function, halting the bacterial infection. The bacterial cell causing the infection is unable to reproduce, and instead produces additional phages. Phages are very selective in the strains of bacteria they are effective against.

<span class="mw-page-title-main">Aztreonam</span> Chemical compound

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

<span class="mw-page-title-main">Colistin</span> Antibiotic

Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as Pseudomonas aeruginosa, Klebsiella pneumoniae, or Acinetobacter. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015.

Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.

<span class="mw-page-title-main">Tigecycline</span> Chemical compound

Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Rifabutin</span> Chemical compound

Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. For active tuberculosis it is used with other antimycobacterial medications. For latent tuberculosis it may be used by itself when the exposure was with drug-resistant TB.

Intralytix, Inc. is a privately held “C” corporation that was incorporated in the State of Maryland on July 28, 1998. Intralytix specializes in bacteriophage-based products used to control bacterial pathogens in environmental, agricultural, food processing, and medical settings.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

<i>Mycobacteroides abscessus</i> Species of bacterium

Mycobacteroides abscessus is a species of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that is a common soil and water contaminant. Although M. abscessus most commonly causes chronic lung infection and skin and soft tissue infection (SSTI), it can also cause infection in almost all human organs, mostly in patients with suppressed immune systems. Amongst NTM species responsible for disease, infection caused by M. abscessus complex are more difficult to treat due to antimicrobial drug resistance.

<span class="mw-page-title-main">Steffanie A. Strathdee</span> Canadian epidemiologist

Steffanie A. Strathdee is the Associate Dean of Global Health Sciences, Harold Simon Professor at the University of California San Diego School of Medicine and Co-Director at the Center for Innovative Phage Applications and Therapeutics. She has been awarded more than US$64 million in federal research grants as a principal investigator. She is known for her work on HIV research and prevention programmes in Tijuana.

<span class="mw-page-title-main">Plazomicin</span> Chemical compound

Plazomicin, sold under the brand name Zemdri, is an aminoglycoside antibiotic used to treat complicated urinary tract infections. As of 2019 it is recommended only for those in whom alternatives are not an option. It is given by injection into a vein.

<span class="mw-page-title-main">Eravacycline</span> Chemical compound

Eravacycline is a synthetic halogenated tetracycline class antibiotic by Tetraphase Pharmaceuticals. It is closely related to tigecycline. It has a broad spectrum of activity including many multi-drug resistant strains of bacteria. Phase III studies in complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) were recently completed with mixed results. Eravacycline was granted fast track designation by the FDA and is currently available in USA.

ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.

<span class="mw-page-title-main">Cefiderocol</span> Antibiotic

Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.

<span class="mw-page-title-main">Robert T. Schooley</span> American infectious disease physician

Robert "Chip" T. Schooley is an American infectious disease physician, who is the Vice Chair of Academic Affairs, Senior Director of International Initiatives, and Co-Director at the Center for Innovative Phage Applications and Therapeutics (IPATH), at the University of California San Diego School of Medicine. He is an expert in HIV and hepatitis C (HCV) infection and treatment, and in 2016, was the first physician to treat a patient in the United States with intravenous bacteriophage therapy for a systemic bacterial infection.

Vincent A. Fischetti is a world renowned American microbiologist and immunologist. He is professor of and head of the Laboratory of Bacterial Pathogenesis and Immunology at Rockefeller University in New York City. His primary areas of research are bacterial pathogenesis, bacterial genetics and genomics, immunology, virology and microbiology, and mechanisms of disease. He was the first scientist to clone and sequence a surface protein on gram-positive bacteria, the M protein from S. pyogenes, and determine its unique coiled-coil structure. He also was the first use phage lysins as a therapeutic and an effective alternative to conventional antibiotics.

References

  1. "Turning A Phage". Turning A Phage. UC San Diego Health. University of California San Diego. Retrieved February 19, 2019.
  2. 1 2 "". Center for Innovative Phage Applications and Therapeutics. Retrieved February 19, 2019.
  3. LaFee, Scott; Buschman, Heather (June 21, 2018). "Turning A Phage". UC San Diego Health Newsroom. Retrieved June 4, 2019.
  4. "". With OK From FDA, UC San Diego Researchers Prepare to Launch Novel Phage Study. Retrieved February 19, 2019.
  5. 1 2 Schooley, Robert (October 2017). "Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection" (PDF). Antimicrobial Agents and Chemotherapy. 61 (10). doi:10.1128/AAC.00954-17. PMC   5610518 . PMID   28807909.
  6. Aslam, Saima; Pretorius, Victor; Lehman, Susan M.; Morales, Sandra; Schooley, Robert T. (2019-04-01). "Novel bacteriophage therapy for treatment of left ventricular assist device infection". The Journal of Heart and Lung Transplantation. 38 (4): 475–476. doi:10.1016/j.healun.2019.01.001. ISSN   1053-2498. PMID   30661974. S2CID   58613504.
  7. Nir-Paz, Ran; Gelman, Daniel; Khouri, Ayman; Sisson, Brittany M; Fackler, Joseph; Alkalay-Oren, Sivan; Khalifa, Leron; Rimon, Amit; Yerushalmy, Ortal (March 2019). "Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination". Clinical Infectious Diseases. 69 (11): 2015–2018. doi:10.1093/cid/ciz222. PMID   30869755.
  8. "Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection". UC Health - UC San Diego. Retrieved 2019-06-04.
  9. Sockett, Liz (December 2017). "Viruses save a man from antibiotic-resistant bacteria". The Guardian. Retrieved June 4, 2019.
  10. Ghorayshi, Azeen (May 2017). "Her Husband Was Dying From A Superbug. She Turned To Sewer Viruses Collected By The Navy". BuzzFeed News. Retrieved June 4, 2019.
  11. Weber, Lauren (May 11, 2018). "Sewage Saved This Man's Life. Someday It Could Save Yours". HuffPost. Retrieved June 4, 2019.
  12. "About the AVRC". Antiviral Research Center. Retrieved June 4, 2019.