Recently, the FDA has proposed even more stringent criteria for commercial automated AST, restricting reportable antimicrobial susceptibilities only to indications studied in clinical trials and listed in the drug label. Increased restriction could interfere severely with off-label AST reporting and antimicrobial prescribing and compromise AMS efforts. The workload for clinical microbiology laboratories would increase. A deficit of reported information would lead to more tests initiated at a clinician’s request, and because the susceptibility of a particular drug-bug combination might not be included in an automated AST panel, the laboratories would have to perform these tests manually, which some may not be either equipped or staffed to do. As AST for some “drug-bug” combinations become more burdensome, clinical microbiology laboratories would be less likely to do it. Without such testing, clinicians’ choices of empiric antimicrobial agents would be less informed, and they would be more likely to prescribe suboptimal but broader-spectrum antimicrobials that might “cover their bases.” Thus, the restrictions would increase the inappropriate prescribing AMS programs aim to reduce.
In the longer term, increased restrictions on commercial automated AST would also harm patient care. Because of high expenses and low profit margins, few companies already undertake antimicrobial development. If it becomes a requirement that companies assess their antimicrobials for multiple indications in clinical trials to have those susceptibilities included in commercial AST panels, more companies might determine that antimicrobial development is too expensive, leaving fewer companies in the field and fewer new antimicrobials in the market. Increased restriction could also slow technological development, with fewer companies and fewer resources devoted to the development of new rapid diagnostic and AST devices.
Rapid organism identification has improved patient care and decreased the time to targeted therapy during treatment scenarios that are measured in minutes and hours. Thus, technology enabling rapid organism identification has resulted in reduced mortality and morbidities, such as length of hospital stay and cost. However, the restrictions described above may slow development of urgently-needed antimicrobial agents and may negatively affect patient care.
Addressing These Challenges
Ideally, pharmaceutical companies, diagnostic device companies, and the FDA Centers that regulate them would align their priorities and marry FDA-approved inclusion of antimicrobial susceptibilities in commercial AST systems with approval of the antimicrobials themselves. However, this is unlikely. Panels for automated systems to determine susceptibility of some Gram-negative strains to drugs such as ceftolozane-tazobactam and ceftazidime-avibactam are being developed, with some likely to be commercially available within the next year.
In the meantime, clinicians can increase awareness of existing challenges to AST, particularly among their colleagues outside of the infectious disease field.
Clinicians also can work with their microbiology laboratories toward manual testing of resistant isolates to determine whether new antimicrobial agents are appropriate. Such testing will take time and effort, but are necessary when it is best for patient care.
Hospitals are on the front lines of the urgent public health threat of antimicrobial resistance. While taking steps to prioritize AMS programs is a good first step, clinicians can deepen their commitment to addressing these concerns by better understanding the factors in play surrounding AST. By working collaboratively with their hospital’s clinical microbiology laboratory, clinicians can move the needle in terms of employing accurate, rapid diagnostics, leading to better patient outcomes.
Dr. Gallagher is a clinical professor at Temple University School of Pharmacy and clinical pharmacy specialist in infectious diseases at Temple University Hospital, both in Philadelphia. He also is the director of the PGY2 Residency in Infectious Diseases Pharmacy at Temple. He is an active member of SIDP.
- Stover, KR, Bland CM, Gallagher JC. The point of antimicrobial susceptibility testing is to inform antimicrobial prescribing. Clin Infect Dis. 2017;64(1):103-104. doi: 10.1093/cid/ciw686.
- The Joint Commission. Approved: new antimicrobial stewardship standard. Joint Commission Perspectives. 2016;36(7). https://www.jointcommission.org/assets/1/6/New_Antimicrobial_Stewardship_Standard.pdf. Accessed April 19, 2017.
- 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. 2016;63(1):83-88. doi: 10.1093/cid/ciw201.
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