MDLinx | December 18, 2017
Antimicrobial resistance is a growing threat not just in the United States, but worldwide. A recent conference, Superbugs and Superdrugs USA, brought together experts on antimicrobial resistance and provided a platform for further discussion of future endeavors to hinder the increasing danger this poses to modern medicine.
In an exclusive interview with MDLinx, Mark Albrecht, PhD, health scientist, Anti-Bacterial (AB) Program, Division of CBRN Countermeasures, Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (DHHS), provides expert insight on antimicrobial resistance and initiatives to curtail the looming threat.
MDLinx: How long has antimicrobial resistance (AMR) been a problem globally and in the United States?
Dr. Albrecht: Resistance to antimicrobial compounds is a well-established process that widely occurs among environmental bacteria to ensure their survival in conditions where there is enormous competition for limited resources. In fact, the genes that confer resistance to antibiotics pre-date the development and use of antibiotics. Because the development of antimicrobial resistance (AMR) is a natural process, either via mutation or acquisition of genes that facilitate resistance, it is only natural that it should occur within bacteria that infect humans. AMR has been an issue ever since [Alexander] Fleming discovered penicillin and stated, ‘The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.’ Unfortunately, due to inappropriate usage, resistance is often seen within just a few years of the introduction of a new antibiotic. The development of effective and rapid POC diagnostics along with new and effective antibiotics and the policies ensuring their appropriate usage and stewardship, are essential to ensuring that we have the tools to tackle the issue of AMR. What was once a rare occurrence has now become an endemic problem within the healthcare setting, within the US alone it is estimated that there are 2 [million] infections and 23,000 deaths annually due to AMR. This costs the US $100 [million] annually. It is predicted that globally this will rise to 10 [million] deaths annually and total economic burden of $10 [trillion] by 2050 if the curve is not bent. Most troubling is that AMR jeopardizes the relative safety of many common medical procedures that we take for granted (hip replacement, chemotherapy, C sections, etc.) and are dependent on the availability of effective antibiotics.
MDLinx: Can you briefly describe the threat of antimicrobial resistance in the United States?
Dr. Albrecht: The CDC has assembled a comprehensive list of urgent, serious, and concerning AMR threats facing public health in the United States. At the top of this list is Clostridium difficile, followed by Carbapenem-resistant Enterobacteriaceae (CRE) and drug-resistant Neisseria gonorrhoeae. The most recent data from the CDC for C. difficile shows that there were 17,354 cases reported to the Emerging Infections Program in 2015. Providing exact numbers of CRE infections is difficult, however, mortality rates are between 40% and 50% in some studies and the total number of reported cases of N. gonorrhoeae in 2016 was 468,514. Identifying where these strains came from can be difficult as some may have already been present and were created through antibiotic overuse. In other cases bacteria harboring genes encoding resistance have come from overseas and were introduced to our healthcare settings where they have taken up residence.
MDLinx: What are we doing to prevent the spread of these superbugs in hospitals and within communities?
Dr. Albrecht: The US government and public advocacy groups are involved in multiple campaigns to mitigate the spread of these bacteria. One such campaign is the Get Smart program, which is a national campaign to improve antibiotic prescribing and use in both outpatient and inpatient settings. This program supports multiple state-based programs modeled on the national effort. In fact, November 13-19, 2017 is the US Antibiotic Awareness Week. Non-profit organizations such as IDSA also support the implementation of antimicrobial stewardship programs within all healthcare settings. Other local, hospital-initiated efforts focus on infection prevention through surveillance, education, and increased hygiene efforts.
MDLinx: Are there initiatives to monitor and improve prescribing behaviors among US physicians?
Dr. Albrecht: The primary resource is the CDC’s National Healthcare Safety Network (NHSN), which is used by health care facilities to electronically report infections, antibiotic use, and resistance. The data provided by facilities, states, and regions is used to track and benchmark antibiotic resistance in bacteria responsible for many health care-associated infections. This information will allow facilities to target areas of concern, to make needed improvements and to track the success of their efforts. In addition, NHSN allows CDC to perform and report national assessments of antibiotic resistance.
MDLinx: Can you briefly describe BARDA initiatives to fix the “broken pipeline” and accelerate antimicrobial development?
Dr. Albrecht: BARDA is a component of the Office of the Assistant Secretary of Preparedness and Response within the Department of Health and Human Services. BARDA’s mission is to save lives and protect America by making available vaccines, treatments, and diagnostics against dire chemical, biological, radiological, nuclear, (Chemical, Biological, Radiological, and Nuclear [CBRN]) threats, pandemic influenza, and emerging infectious diseases. The lack of effective antibacterials impedes our ability to respond to any public health emergency due to CBRN threat agents, pandemic influenza, and emerging infectious diseases. As part of BARDA’s end-to-end response to CBRN and emerging infectious disease threats, BARDA is investing in new antimicriobials to address Bacillus anthracis, Burkholderia mallei, Burkholderia pseudomallei, Yersinia pestis, Francisella tularensis, and the threat of secondary multi-drug resistant Gram-negative bacterial infections, that can occur as a consequence of CBRN threats, pandemic influenza and other emerging diseases.
Currently, there is a market failure due in part to the low return on investment that antibiotics generate. As a consequence, we are not discovering and developing new and effective antibiotics fast enough to counter the growing threat of drug-resistant bacteria and biothreats. To address this issue BARDA has formed 11 public-private partnerships with companies to develop 13 antimicrobial products. Since 2010, we have provided $1.72 [billion] to support the development of a mix of early- and late-stage products with an emphasis on products in phase 2 and phase 3 development. These partnerships take the form of contracts, which allow the government to partner with a company and share the cost of developing a new antibiotic. Through these arrangements, the government is able to not only provide funding but access to core services such as the BARDA Non-Clinical Development Network, Clinical Trials Network, and manufacturing services as well as Subject Matter Experts who have spent decades working in the pharmaceutical industry. To extend our funding and development capabilities we are working with other international funding agencies like the Innovative Medicines Initiative (IMI) in the European Union to support the development of needed antibiotics.
To date, the BARDA model has resulted in 34 FDA approvals of critical drugs, vaccines and diagnostics, one of which is meropenem and vaborbactam for injection (Vabomere), The Medicines Company's new antibiotic developed to treat serious Gram-negative complicated urinary tract infections. BARDA is also supporting Achaogen’s development and NDA filing for plazomicin and the development and filing preparations for eravacycline from Tetraphase Pharmaceuticals. BARDA is anticipating more NDA fillings in the next 12 months.
BARDA is also a funding partner of CARB-X, a global public-private innovation fund that is a $455 [million] partnership with NIAID and Welcome Trust. It is focused on supporting the early stage, hit to lead through phase 1 development of antibiotic candidates. There are presently 24 pre-clinical antibacterial candidates in the portfolio. We believe that these combined efforts will and are making an impact to accelerate antimicrobial development.
Mark Albrecht, PhD, joined the Biomedical Advanced Research and Development Authority (BARDA) in March 2012. As a Project Officer within the Anti-Bacterials Branch, he provides strategic planning and technical support to public-private partnerships that advance the development and marketing approval of antibiotics for biodefense preparedness and commercial indications. Dr. Albrecht also works with PHEMCE partners to strengthen Government inter-agency collaborations, coordinate efforts to advance the development of bio-defense medical countermeasures, and ensure that Government agency portfolios are properly aligned. Prior to his arrival at BARDA, Dr. Albrecht was a Senior Staff Scientist at the Biological Defense Research Directorate (BDRD) within the Naval Medical Research Center (NMRC) were he was responsible for leading the Navy’s programs on passive immune-therapy against anthrax and the development of multi-valent/agent vaccination strategies against Bacillus anthracis and Yersinia pestis based on recombinant proteins and DNA. In his roles at BARDA and BDRD Dr. Albrecht has facilitated and maintained numerous public-private partnerships between industry and Government organizations. Dr. Albrecht received his BA in Biology from the Whitman College, Walla Walla, WA. He went on to attend the University of California Riverside where he received his PhD in Microbiology while studying the properties of sensitivity and resistance of Pseudomonas aeruginosa and Burkholderia cepacia to antimicrobial peptides and the role of alginate lyase during P. aeruginosa biofilm formation.