The world is in the midst of a public health crisis, thanks to emerging superbugs that demonstrate resistance to all existing antibiotics. This makes choosing the right antibiotic for an infection paramount, as well as identifying emergent resistance. Neither can be done without frontline testing in the clinical laboratory.
Yet clinical laboratories are using 40-year-old technology and struggling to generate accurate and actionable antimicrobial susceptibility reports, write Romney Humphries, PhD, and Janet Hindler, MCLS, MT(ASCP), in a recent article in Clinical Infectious Diseases. Humphries is the chief quality officer in pathology and laboratory medicine, and Hindler is a senior specialist in clinical microbiology at the UCLA David Geffen School of Medicine.
The authors identified three key challenges to improved testing and reports:
- Extensive delays between the update of a clinical breakpoint and its clearance on commercial antimicrobial susceptibility testing (cAST) devices. This compromises patient safety, they wrote, because laboratories may not detect resistance while emerging resistance may go undetected.
Solutions include improving cooperation between the Food and Drug Administration (FDA) and diagnostic manufacturers to identify an optimal plan for updating breakpoints; identifying a regulatory mechanism to set time limits for in-vitro diagnostic (IVD) breakpoint updates; and having the FDA and the Centers for Disease Control and Prevention (CDC) develop a set of challenge isolates for testing with updated breakpoints as soon the breakpoint needs updating. They should then add it to a new FDA-CDC Antimicrobial Resistance Bank.
- Tests for newer drugs are not available on cAST devices. This compromises patient safety, they wrote, because some drugs, such as ceftazidime-avibactam and ceftolozane-tazobactam, cannot be used without AST. In addition, emerging resistance may go undetected.
Overcoming this challenge requires that the FDA and pharmaceutical and diagnostic manufacturers work together prior to a new drug application submission to identify an optimal plan for adding the drug to the IVD. In addition, diagnostic manufacturers need FDA breakpoints available as soon as possible so they can begin test development, and the FDA and CDC should work with pharmaceutical manufacturers to develop a set of challenge isolates for testing during new drug development.
- The FDA does not provide breakpoints for organisms that may not have been included in or did not perform reliably during the pharmaceutical manufacturer’s clinical trial (e.g., meropenem and Acinetobacter). This compromises patient safety because antimicrobial agents are frequently used off label.
To address this challenge, the authors recommend that the FDA reconsider the need for clinical data to determine that an IVD test performs reliably. Instead, it should consider the pros and cons to patient safety and to the public health of various breakpoint-setting rules.
“Prompt attention to these man-made challenges at a national level is essential,” wrote Humphries and Handler, “as these cripple laboratories’ ability to perform AST and generate clinically relevant data on antimicrobial resistance.”