Antimicrobial resistance has intensified the need for new treatment options that can aid patients who have complicated infections. Multidrug-resistant (MDR) gram-negative organisms, along with limited treatment options, complicate the management of these infections. With the emergence of carbapenem resistance in Enterobacterales
, Pseudomonas aeruginosa
, and Acinetobacter baumannii
, the urgent threat to public health has grown. According to the CDC’s 2019 Antibiotic Resistance Threat Report, nearly 3 million antibiotic-resistant infections occur each year in the US, with over 35,000 resulting deaths. In response to this increasing issue, the effort to combat resistant bacteria has become an international priority for global health security.
In anticipation of the continued emergence of treatment-resistant pathogens, the FDA has worked to facilitate expedited development and review of new drugs/biologics by establishing the Fast Track program. The Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act includes the Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections. QIDP-designated drugs are eligible for fast track designation and priority review. Under GAIN, a drug may be designated as a QIDP if it meets applicable criteria, including that it not only must be intended for serious or life-threatening conditions but also must demonstrate the potential to address unmet medical needs.
A recent QIDP designee is cefiderocol, the first siderophore antibiotic. Cefiderocol is currently approved for the treatment of adults with complicated urinary tract infections, including pyelonephritis. Evaluations are still underway for its considered use as treatment of nosocomial pneumonia and carbapenem-resistant infections. The drug is a siderophore cephalosporin with potent in vitro
activity against carbapenem-resistant Enterobacteriaceae and drug-resistant nonfermenting gram-negative bacilli. Because of its mechanism of action, it achieves high penetration into the periplasmic space of bacterial cells. In addition to being able to overcome this barrier effectively, it also demonstrates an increased ability to remain protected from beta-lactamases produced by most gram-negative bacteria. It is stable against all known classes of beta-lactamases, including both the metallo-type (VIM, IMP, NDM) and serine-type (KPC, OXA) carbapenemases. The recommended dosing for this injectable is a 2g intravenous infusion over 3 hours every 8 hours for 7 to 14 days, depending on the severity of the infection.
Centers for Disease Control and Prevention website. 2019 AR Threats Report. https://www.cdc.gov/drugresistance/biggest-threats.html. Updated June 18, 2020. Accessed June 30, 2020.
U.S. Food and Drug Administration website. Fast Track Designation Requests. https://www.fda.gov/drugs/ind-activity/fast-track-designation-requests. Updated January 24, 2020. Accessed June 30, 2020.
U.S. Food and Drug Administration website. FDA approves new antibacterial drug to treat complicated urinary tract infections as part of ongoing efforts to address antimicrobial resistance.
https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibacterial-drug-treat-complicated-urinary-tract-infections-part-ongoing-efforts. Updated November 14, 2019. Accessed June 30, 2020.
U.S. Food and Drug Administration website. Qualified Infectious Disease Product Designation Questions and Answers Guidance for Industry. https://www.fda.gov/media/111091/download. Updated January 2018. Accessed June 30, 2020.
Wu JY, Srinivas P, Pogue JM. Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms. Infect Dis Ther. 2020;9(1):17-40. doi:10.1007/s40121-020-00286-6