Don't Get Wound Up: Revised Fluoroquinolone Breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

Fluoroquinolones remain some of the more commonly prescribed antimicrobial agents in the United States, despite the wide array of reported side effects that are associated with their use. In 2019, the Clinical and Laboratory Standards Institute revised the fluoroquinolone antimicrobial susceptibility testing breakpoints for both Enterobacteriaceae and Pseudomonas aeruginosa. This breakpoint revision was deemed necessary on the basis of pharmacokinetic and pharmacodynamic analyses suggesting that the previous breakpoints were too high, in addition to the inability of the previous breakpoints to detect low-level resistance to this antibiotic class. In this minireview, we review the published data in support of this revision, as well as the potential challenges that these breakpoint revisions are likely to pose for clinical laboratories.A ntimicrobial susceptibility testing (AST) is one of the most important functions of a clinical microbiology laboratory. In the United States, as well as in many other countries, Clinical and Laboratory Standards Institute (CLSI) M100 performance standards (1) are widely used for the interpretation of AST results. Regardless of whether testing is performed by disk diffusion (i.e., Kirby-Bauer method) or MIC-based methods, results are compared with established criteria that enable the laboratory to categorize the result as susceptible, intermediate, or resistant to a given antibiotic.The setting of AST breakpoints is a complex and dynamic process that integrates microbiological, pharmacokinetic (PK)/pharmacodynamic (PD), and clinical outcome data (2, 3). In 2019, the 29th edition of the CLSI M100 supplement features several breakpoint revisions for a number of bacteria (4); however, revision of the fluoroquinolone (FQ) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa will arguably affect the largest number of isolates tested in clinical laboratories. A comparison of the previous and revised CLSI FQ breakpoints, as well as the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (5), is shown in Table 1. In 2017, EUCAST lowered the FQ breakpoints for several organisms (including Grampositive bacteria). It is important to note that the revision of the CLSI FQ breakpoints was limited solely to Enterobacteriaceae and P. aeruginosa and other bacteria were not included in this change. In addition, there are currently no CLSI-approved breakpoints for moxifloxacin for either Enterobacteriaceae or P. aeruginosa. In this minireview, we review the evidence for the necessity of this FQ breakpoint revision, as well as the issues this is likely to pose for clinical microbiology laboratories. REVIEW OF FLUOROQUINOLONESFQs are a class of broad-spectrum antibiotics that inhibit bacterial DNA synthesis by interfering with the enzymes DNA gyrase and topoisomerase IV. Although the individ-Citation Van TT, Minejima E, Chiu CA, Butler-Wu SM. 2019. Don't get wound up: revised fluoroquinolone breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa. J Clin Microb...

Estimating Factors Related to Fluoroquinolone Resistance Based on One Health Perspective: Static and Dynamic Panel Data Analyses From Europe

“…Based on this existing research, we employed static and dynamic models in panel studies to explore factors related to the resistance of fluoroquinolones (FQs), which are regarded as a critically important antimicrobial for human medicine and one of the antibiotic groups most frequently administered in veterinary medicine (Van et al, 2019). Consequently, the emergence of resistance to FQs has also become a major public health concern (Almalki et al, 2017).…”

QSAR Models for Active Substances against Pseudomonas aeruginosa Using Disk-Diffusion Test Data

“…However, this cut-off is not without problems, since clinical breakpoints used in the medical practice are substance-specific, but they are only available for a small number of authorized antibiotics, but not for the largest number of compounds tested for scientific purposes outside a clinical setting. Moreover, antimicrobial susceptibility testing breakpoints are established taking into account not only in vitro results of a large number of microbial isolates, but also pharmacokinetic, pharmacodynamics and clinical considerations specific for each antibiotic [ 36 ]. Furthermore, experts in the field of disk diffusion testing emphasize that IZ is dependent on the diffusion rate (through the agar gel) of the tested compound, which in its turn is dependent on certain drug features, such as its size or partition coefficient [ 24 ].…”

Appropriateness of Empirical Fluoroquinolones Therapy in Patients Infected with Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa: The Importance of the CLSI Breakpoints Revision

“…The setting of AST breakpoints is a complex and dynamic process that integrates microbiological, pharmacokinetic (PK)/pharmacodynamic (PD), and clinical outcome data. 23 Therefore, changes in the breakpoints can reflect the changes in the antimicrobial susceptibility of bacteria and other characteristics of antibiotics, which should be used as an important reference for empirical antibiotic therapy.…”

“…The CLSI published revisions to the breakpoints of ciprofloxacin and levofloxacin against Enterobacter (except Salmonella) and Pseudomonas aeruginosa in the CLSI M100 in 2019 (Table 1) after reviewing the data compiled and used by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) because there was evidence that the breakpoints of ciprofloxacin and levofloxacin before 2019 were too high to detect lowlevel FQs resistance among Enterobacteriaceae and Pseudomonas aeruginosa strains. 23 We assume that the CLSI breakpoint revision could have an impact on susceptibility rates of FQs, with concomitant changes in antibiotic prescriptions by physicians.…”