Susceptibility Testing and Reporting of New Antibiotics with a Focus on Tedizolid: An International Working Group Report

Abstract

Inappropriate use and overuse of antibiotics are among the most important factors in resistance development, and effective antibiotic stewardship measures are needed to optimize outcomes. Selection of appropriate antimicrobials relies on accurate and timely antimicrobial susceptibility testing. However, the availability of clinical breakpoints and in vitro susceptibility testing often lags behind regulatory approval by several years for new antimicrobials. A Working Group of clinical/medical microbiologists from Brazil, Canada, Mexico, Saudi Arabia, Russia and the UK recently examined issues surrounding antimicrobial susceptibility testing for novel antibiotics. While commercially available tests are being developed, potential surrogate antibiotics may be used as marker of susceptibility. Using tedizolid as an example of a new antibiotic, this special report makes recommendations to optimize routine susceptibility reporting.

<p>Tedizolid phosphate for the treatment of acute bacterial skin and skin-structure infections: an evidence-based review of its place in therapy</p>

“…This possibly relies on the fact that in contrast to linezolid, tedizolid largely retains in vitro activity against Gram-positive bacteria harboring the cfr gene–encoded methylase enzyme 21,22. On the other hand, chromosomal mutations in domain V of rRNA or ribosomal L3 or L4 proteins have been reported to confer resistance to both linezolid and tedizolid 11,23. An additional resistance mechanism has been found in enterococci, owing to the presence of an ABC transporter codified by the optrA gene carried by plasmids, which confers resistance to phenicols and oxazolidinones.24…”

Reporting Elevated Vancomycin Minimum Inhibitory Concentration in Methicillin-Resistant Staphylococcus Aureus : Consensus by An International Working Group

“…The precise determination of vancomycin MIC is complex, due to the limitations of current methods for testing susceptibility [15], some of which may be inherent of the method itself and not linked to the conditions used [20]. A number of methods are currently used for antibiotic susceptibility testing and can be automated (i.e., Vitek R 2, BD Phoenix™, MicroScan, Sensititre™) or manual (i.e., disk diffusion, broth microdilution and Etest) [21], although broth microdilution is the standard method used to define vancomycin MIC [15,20]. Importantly, however, discrepancies in MIC values have been reported, with a one to two dilution difference in the obtained MIC values apparent when the results of various methods are compared [20,22,23].…”

The quality of antimicrobial discs from nine manufacturers—EUCAST evaluations in 2014 and 2017

“…Disc diffusion is used worldwide for antimicrobial susceptibility testing (AST). The method is simple, flexible and inexpensive, traits that have become increasingly important with the introduction of new agents, where the slow implementation in automated AST systems has become a problem [1]. However, users and manufacturers may consider the simplicity and flexibility of the method a carte blanche for ignoring the need for stringent quality control (QC).…”