10 x '20 Progress--Development of New Drugs Active Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America

Abstract

Infections caused by antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's "10 × '20 Initiative."

The re-emergence of natural products for drug discovery in the genomics era

“…The current rate of the introduction of new antimicrobials may not be sufficient to cope with the emergence of bacteria and fungi that are resistant to available agents [196][197][198][199] . The situation is particularly acute in the case of drug-resistant Gram-negative bacterial infections, because very few new compounds are in development for such uses 200 . The question is whether or not natural products can be useful in finding such agents.…”

The emerging problem of bacterial resistance in cancer patients; proceedings of a workshop held by MASCC “Neutropenia, Infection and Myelosuppression” Study Group during the MASCC annual meeting held in Berlin on 27–29 June 2013

“…Boucher et al [58] have summarized the current candidate drugs under development including ceftaroline/tazobactam, ceftozolane/tazobactam, ceftaroline/ avibactam, ceftazidime/avibactam, imipenem/MK-7655 (a new beta-lactamase inhibitor), plazomycin, eravacycline, and brilacidin. Some of these drugs have already been introduced but there are little or no published data about use in FNP.…”

Design, synthesis and biological evaluation of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides as potent Gram-positive antibacterial agents

“…Among them, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, extended spectrum beta-lactamase enterobacteria, Clostridium difficile as well as MDR Gramnegative bacteria Pseudomonas aeruginosa are the most important cause of concern 1,[4][5][6][7] . The problem of MDROs is particularly evident in hospital settings where the antibiotic usage reaches maximum, but is also found in community-acquired infections.…”