Antimicrobial resistance occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria, viruses, protozoa, and fungi. Together, these adaptations fall under the AMR umbrella, posing significant challenges to healthcare worldwide. Misuse and improper management of antimicrobials are primary drivers of this resistance, though it can also occur naturally through genetic mutations and the spread of resistant genes.
A bacteriophage, also known informally as a phage, is a virus that infects and replicates within bacteria and archaea. The term is derived from Ancient Greek φαγεῖν (phagein) 'to devour' and bacteria. 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.
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
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.
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.
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.
UC San Diego Health is the academic health system of the University of California, San Diego in San Diego, California. It is the only academic health system serving San Diego and has one of three adult Level I trauma centers in the region. In operation since 1966, it comprises three major hospitals: UC San Diego Medical Center in Hillcrest, Jacobs Medical Center in La Jolla, and East Campus Medical Center at UC San Diego Health in East County. The La Jolla campus also includes the Moores Cancer Center, Shiley Eye Institute, Sulpizio Cardiovascular Center, and Koman Family Outpatient Pavilion, and the health system also includes several outpatient sites located throughout San Diego County. UC San Diego Health works closely with the university's School of Medicine and Skaggs School of Pharmacy to provide training to medical and pharmacy students and advanced clinical care to patients.
Douglas D. Richman is an American infectious diseases physician and medical virologist. Richman's work has focused on the HIV/AIDS pandemic, since its appearance in the early 1980s. His major contributions have been in the areas of treatment, drug resistance, and pathogenicity.
In 2016, the prevalence rate of HIV/AIDS in adults aged 15–49 was 0.3%, relatively low for a developing country. This low prevalence has been maintained, as in 2006, the HIV prevalence in Mexico was estimated at around 0.3% as well. The infected population is remains mainly concentrated among high risk populations, men who have sex with other men, intravenous drug users, and commercial sex workers. This low national prevalence is not reflected in the high-risk populations. The prison population in Mexico, faces a fairly similar low rate of around 0.7%. Among the population of prisoners, around 2% are known to be infected with HIV. Sex workers, male and female, face an HIV prevalence of around 7%. Identifying gay men and men who have sex with other men have a prevalence of 17.4%. The highest risk-factor group is identifying transgender people; about 17.4% of this population is known to be infected with HIV. Around 90% of new infections occur by sex-related methods of transmission. Of these known infected populations, around 60% of living infected people are known to be on anti-retroviral therapy (ART).
Autographiviridae is a family of viruses in the order Caudovirales. Bacteria serve as natural hosts. There are 373 species in this family, assigned to 9 subfamilies and 133 genera.
Enzybiotics are an experimental antibacterial therapy. The term is derived from a combination of the words “enzyme” and “antibiotics.” Enzymes have been extensively utilized for their antibacterial and antimicrobial properties. Proteolytic enzymes called endolysins have demonstrated particular effectiveness in combating a range of bacteria and are the basis for enzybiotic research. Endolysins are derived from bacteriophages and are highly efficient at lysing bacterial cells. Enzybiotics are being researched largely to address the issue of antibiotic resistance, which has allowed for the proliferation of drug-resistant pathogens posing great risk to animal and human health across the globe.
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. 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. The first planned clinical trial is set to look at otherwise healthy cystic fibrosis patients that are shedding Pseudomonas aeruginosa.
Locus Biosciences is a clinical-stage pharmaceutical company, founded in 2015 and based in Research Triangle Park, North Carolina. Locus develops phage therapies based on CRISPR–Cas3 gene editing technology, as opposed to the more commonly used CRISPR-Cas9, delivered by engineered bacteriophages. The intended therapeutic targets are antibiotic-resistant bacterial infections.
Benjamin K. Chan is a research scientist at Yale University in the department of Ecology and Evolutionary Biology. He was born in 1980 to a U.S. Asian father, an engineer, and an American mother. He is known for his work in phage therapy exploiting genetic trade-offs to treat antibiotic resistant bacterial infections. He currently lives in Guilford, Connecticut.
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.
Diane Havlir is an American physician who is a Professor of Medicine and Chief of the HIV/AIDS Division at the University of California, San Francisco. Her research considers novel therapeutic strategies to improve the lives of people with HIV and to support public health initiatives in East Africa. She was elected to the National Academy of Medicine in 2019.
Martha Rebecca Jane Clokie is a professor of microbiology at the University of Leicester. Her research investigates the identification and development of bacteriophages that kill pathogens in an effort to develop new antimicrobials.
Ruth S. Waterman is an American anesthesiologist, Chair of the Department of Anesthesiology at UC San Diego Health, Associate Clinical Professor at UC San Diego School of Medicine, and Co-Founder and Chief Medical Officer of Commence Bio, a company that specializes in next generation stem cell therapy and cancer immunotherapy. Waterman is known for developing stem cell-based therapies to help patients with pain and advancing methods to personalize pain medicine based on pre-surgery genetic testing.
David "Davey" M. Smith, is an American translational research virologist, chief of the Division of Infectious Diseases and Global Public Health at the University of California San Diego, co-director of the San Diego Center for AIDS Research, and vice chair of research in the Department of Medicine at UC San Diego. His research interests include transmission, prevention, and treatment of both HIV and SARS-CoV2 (COVID-19). Since joining the UC San Diego faculty in 2003, Smith has been awarded more than $37 million in federal funding as a principal investigator. His research interests include transmission, prevention, and treatment of both HIV and COVID-19.
Monica Malta is a Brazilian researcher who works mostly to address health inequalities faced by LGBTQ persons. She is currently a professor at the University of Toronto and a scientist at the Centre for Addiction and Mental Health. She was elected a TED fellow in 2022.
