2019 Fluoroquinolone Breakpoints Revised for Enterobacteriaceae and Pseudomonas aeruginosa
A revision to the fluoroquinolone antimicrobial susceptibility testing breakpoints for 2 bacteria comes following evidence that previous breakpoints were too high to detect low-level antibiotic resistance.
A recent update by the Clinical Laboratories Standards Institute (CLSI) has revised the fluoroquinolone antimicrobial susceptibility testing (AST) breakpoints for both Enterobacteriaceae and Pseudomonas aeruginosa, but the authors on a new paper about the revisions question whether the updated breakpoints have enough teeth to reduce the problem of fluoroquinolone resistance.
Fluoroquinolones are a class of antibiotics commonly used to treat a range of bacterial infections, and breakpoints set for these and other antibiotics denote the concentration at which an antibiotic agent can or cannot treat a certain bacterial infection. There were more than 30 million oral prescriptions for fluoroquinolones dispensed in the United States in 2014, and the new revision of the fluoroquinolone breakpoints for Enterobacteriaceae and P aeruginosa will arguably impact the largest number of isolates tested in clinical laboratories, the investigators noted.
The paper, published in the Journal of Clinical Microbiology, reviews the published data supporting the recent revision of fluoroquinolone antimicrobial susceptibility testing breakpoints for Enterobacteriaceae and P aeruginosa. The revision, based on pharmacokinetics/pharmacodynamics (PK/PD) and clinical outcome data, reflects analyses suggesting that the previous breakpoints were too high.
In an interview with Contagion®, study co-author Susan Butler-Wu, PhD, of the University of Southern California’s Keck School of Medicine, explained why the 29th edition of the AST Supplement M100 sets revised fluoroquinolone breakpoints for Enterobacteriaceae and P aeruginosa. “There are 2 components to the breakpoint change. One is that essentially, we’ve known for some time that there are strains that have reduced susceptibility to fluoroquinolones that were testing susceptible with the previous breakpoints. What that in theory allows to happen is that then because they already have some resistance mutations that patients may be more likely to fail therapy,” explained Butler-Wu. “The other driver in revising the breakpoints was data based on PK/PD studies.”
The paper’s authors note that low-level fluoroquinolone resistance, which in many cases has been undetectable by the previous breakpoints, can lead to the development of higher-level resistance. The new revision comes following evidence that pre-2019 breakpoints for ciprofloxacin and levofloxacin were too high to detect low-level fluoroquinolone resistance in Enterobacteriaceae and P aeruginosa. In addition, a study of E coli strains with reduced fluoroquinolone susceptibility colonizing the intestinal tracts of hospitalized patients found that nearly 40% of isolates tested would not have been characterized as having reduced susceptibility to fluoroquinolones based on the previous breakpoints, despite having genotypically confirmed resistance mutations.
What remains to be seen, the investigators pointed out, is how clinical laboratories will face the challenge of running laboratory verifications of these breakpoints considering that no commercial AST systems are currently cleared for the 2019 breakpoints. “We don’t actually know how quickly labs are going to adopt these changes, and that’s a really important question. We might have all these great breakpoints but if labs aren’t able to implement them then that can be problematic,” said Butler-Wu. “It’s a regulatory issue, and that’s the crux of the problem. The devices are FDA-cleared with breakpoints that went to the FDA. If you’re going to use your device with a different breakpoint it’s considered an off-label use and you have to do an extensive validation.”
In community hospital settings without a dedicated doctor-level clinical microbiologist, labs may be reluctant to adopt new breakpoints, said Butler-Wu. “There’s a disconnect between what the breakpoints are and what labs are able to actually operationalize for a variety of reasons,” she explained. “This issue that we have with breakpoints not changing at the regulatory level is probably a really unspoken issue that’s driving resistance and inappropriate use of antibiotics.”