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Antimicrobial susceptibility testing (AST) for newer antibiotics is falling behind because there is a lag time between FDA approval and inclusion in commercial AST devices.
Antimicrobial susceptibility testing (AST) helps institutions understand their local ecology, guides their decisions about optimal treatment for often critically-ill patients, and helps them monitor the emergence of resistance.1
Without it, the risk of inappropriate antibiotic prescribing, and the poor patient outcomes that could result, increases. Antimicrobial stewardship without AST is virtually impossible. Unfortunately, widespread adoption of good AST practices faces a number of regulatory and institutional hurdles.
AST for newer antibiotics such as ceftolozane-tazobactam and ceftazidime-avibactam is often hampered by an unacceptably long lag time between FDA approval and inclusion in AST.2 One contributor to this is a disconnect at the FDA between the accelerated approval process for drugs-particularly antibiotics-and the process for devices. While manual tests have slowly made their way to the market, FDA-approved automated commercial AST devices still do not include susceptibility to these new agents.1-3
Related article: How Pharmacists Can Fight Antimicrobial Resistance
Further delays exist between updates in breakpoints, the chosen concentration of an antibiotic that defines whether a given bacteria is susceptible or resistant, and implementation of those updated breakpoints in AST systems.2,3 Automated commercial AST devices must use breakpoints established by the FDA. However, the FDA establishes these breakpoints when drug manufacturers submit individual new drug applications or when device manufacturers submit requests to revise the breakpoints. The agency has been slow to update breakpoints in response to emerging data, and manufacturers seldom proactively submit requests to update breakpoints within 90 days, as the FDA suggests.
Resource-poor labs also contribute to lukewarm AST uptake. Kirby-Bauer disks have been available for ceftolozane-tazobactam and ceftazidime-avibactam for some time, and they are relatively simple to use. However, clinical laboratories have been unwilling to use them. Many have become stymied in the face of health-system bureaucracy and have been slow to check for availability of FDA-cleared testing.
Incremental steps have been taken at the federal level to address regulatory barriers to AST. In the meantime, there are a number of opportunities to support AST efforts on a departmental and institutional level.
Related article: Where Are the New Antibiotics?
Clinicians, pharmacists, clinical microbiology laboratories, and infectious disease/infection control departments can begin to address the challenges to AST by improving communication and dismantling the silos. They can work together to communicate to hospital administrators that AST-and timely implementation of AST for new antimicrobial agents and updated breakpoints-is critical for patient care. Faster implementation of AST for new antimicrobials and updated breakpoints is cost effective: it might appear to cost more up front, but poor patient outcomes are just as expensive, if not more so.
Clinical laboratories can also check more frequently for newly available testing and implement new tests more quickly once they become available. Importantly, in light of the crucial role AST plays in patient care and antimicrobial stewardship, hospitals can recognize and appreciate the value of clinical microbiology laboratories.
1. Motyl M. Coordinated development of antimicrobial drugs and antimicrobial susceptibility tests: Pharmaceutical company experience and perspective. Presented at: FDA Workshop on Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Tests, Silver Spring, MD, Sept. 29, 2016. Available at http://bit.ly/2wrS7fz. Accessed June 7, 2017.
2. Humphries RM, Hindler JA. Emerging resistance, new antimicrobial agents… but no tests! The challenge of antimicrobial susceptibility testing in the current U.S. regulatory landscape. Clin Infect Dis. 2916;63(1):83-88.
3. Krause K. AST device development: the pharma perspective. Presented at: FDA Workshop on Coordinated Development of Antimicrobial Drugs and Antimicrobial Susceptibility Tests, Silver Spring, MD, Sept. 29, 2016. Available at http://bit.ly/2wrrEyD. Accessed June 7, 2017.