Bad Bugs Need Drugs: An Update on the Development Pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America (original) (raw)
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Antimicrobial resistance, which has been reported against almost every antibiotic discovered, is one of the most urgent public health problems, threatening to undermine the effectiveness of infectious disease treatment worldwide. Since penicillin ushered in the antibiotic era in the mid 20th century, the scientific world had engaged in a war between the development of antibac-terial agents and bacterial resistance. During the first decade of the 21st century, grave concern has been expressed over the evolution of multi-drug resistant staphylococci, enterococci, and mycobacteria, which pose serious clinical and public health challenge to humans. The present picture is frighteningly similar to the pre-antibiotic era, with reports of nosocomial spread and intercontinental dissemination of multi-drug resistant bacteria. For infected patients, there is no magic bullet. The microbial pathogens appear to be gaining the upper hand, coupled with a recent dramatic reduction in antibiotic research by pharmaceutical companies because of the high cost of drug research. Several compounds that have recently been developed or resurrected to treat gram-positive infections are still unable to meet the armamentarium of resistance mechanisms of these pathogens. The situation is worse for gram-negative organisms, where no new drug is currently being developed against them. A multidisciplinary approach to combat resistance is required, which must be applied, sustained, and continuously refined. The key components for maintaining effective antimicrobial chemotherapy will include better use of existing agents, coupled with continuous investment in new and innovative technologies, which must include diagnostics and vaccines in addition to new antimicrobial agents.
The Journal of infectious diseases, 2017
Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant Gram-negative bacilli continue to cause unacceptable morbidity and mortality. Antibacterial agents have been traditionally studied in non-inferiority clinical trials that focus on one site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, towards this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific cli...
Update on antibacterial agents: current challenges and recent initiatives
Sri Lanka Journal of Surgery, 2017
Antibacterial agents (ABAs) contribute significantly to reduce morbidity and mortality of bacterial infections as well as play a crucial role in the success of major advances in medicine such as organ transplants, advanced surgeries, cancer chemotherapy and cardiac surgery. However, their success as well as their very existence itself are under threat due to two major problems, one is antibacterial resistance (ABR) and the other is discovery void. A 2014 report by the World Health Organization (WHO) warns that bacteria that cause common health-care associated and community-acquired infections exhibit high resistance rate in all WHO regions. This threat has been endorsed by many organizations including Centres for Disease Control and Prevention (CDC), Infectious Diseases Society of America, and other UN bodies. Though bacteria can develop resistance spontaneously through mutation, the escalating public health threat of ABR is mainly driven by both appropriate and inappropriate use of ABAs in humans, animals, food production, agriculture, and aquaculture. Several initiatives at different levels have been launched to combat ABR. Development of new ABAs which feature new target or mode of action by pharmaceutical industries has the potential to address the problem of ABR. However, hardly any new ABAs featuring new target or mode of action came to market in the last two decades due to economic and regulatory obstacles. Collaboration between industry, government bodies and academic institutions in the exploration of new ABAs, offering incentives, fast tracking market authorization are some of the initiatives recommended by the WHO to address this issue of dry antibiotic pipeline. Rational use of ABAs, implementation of antibiotic stewardship programmes, and adherence to strategies which minimise spread of resistant bacteria such as hand-washing and infection control measures are few key activities that can be incorporated in clinical practice.
Annals of internal medicine, 2016
A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane-tazobactam, and ceftazidime-avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost. Data sources were FDA approval packages and databases (January 2010 to December 2015); the Red Book (Truven Health Analytics); Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (FDA); and supplementary information from company filings, press releases, and media reports. Four antibiotics were approved for acute bacterial skin and skin-structure infection. Seven had similar mechanisms of action to those of previously approved drugs....
Trends in Antimicrobial Drug Development: Implications for the Future
Clinical Infectious Diseases, 2004
The need for new antimicrobial agents is greater than ever because of the emergence of multidrug resistance in common pathogens, the rapid emergence of new infections, and the potential for use of multidrug-resistant agents in bioweapons. Paradoxically, some pharmaceutical companies have indicated that they are curtailing anti-infective research programs. We evaluated the United States Food and Drug Administration (FDA) databases of approved drugs and the research and development programs of the world's largest pharmaceutical and biotechnology companies to document trends in the development of new antimicrobial agents. FDA approval of new antibacterial agents decreased by 56% over the past 20 years (1998-2002 vs. 1983-1987).
The Antimicrobial Resistance Crisis: Causes, Consequences, and Management
Frontiers in Public Health, 2014
The antimicrobial resistance (AMR) crisis is the increasing global incidence of infectious diseases affecting the human population, which are untreatable with any known antimicrobial agent. This crisis will have a devastating cost on human society as both debilitating and lethal diseases increase in frequency and scope. Three major factors determine this crisis: (1) the increasing frequency of AMR phenotypes among microbes is an evolutionary response to the widespread use of antimicrobials; (2) the large and globally connected human population allows pathogens in any environment access to all of humanity; and (3) the extensive and often unnecessary use of antimicrobials by humanity provides the strong selective pressure that is driving the evolutionary response in the microbial world. Of these factors, the size of the human population is least amenable to rapid change. In contrast, the remaining two factors may be affected, so offering a means of managing the crisis: the rate at which AMR, as well as virulence factors evolve in microbial world may be slowed by reducing the applied selective pressure. This may be accomplished by radically reducing the global use of current and prospective antimicrobials. Current management measures to legislate the use of antimicrobials and to educate the healthcare world in the issues, while useful, have not comprehensively addressed the problem of achieving an overall reduction in the human use of antimicrobials. We propose that in addition to current measures and increased research into new antimicrobials and diagnostics, a comprehensive education program will be required to change the public paradigm of antimicrobial usage from that of a first line treatment to that of a last resort when all other therapeutic options have failed.