Evaluating the Rapid Emergence of Daptomycin Resistance in Corynebacterium : a Multicenter Study

Abstract

Background: Members of the genus Corynebacterium are increasingly recognized as pathobionts and can be very resistant to antimicrobial agents. Previous studies have demonstrated that Corynebacterium striatum can rapidly develop high-level daptomycin resistance (HLDR) (minimum inhibitory concentration [MIC] ≥256 μg/mL). Here we conducted a multi-center study to assay for this in vitro phenotype in diverse Corynebacterium species. Methods: Corynebacterium clinical isolates (n=157) from four medical centers were evaluated. MIC values to daptomycin, vancomycin, and telavancin were determined before and after overnight exposure to daptomycin to identify isolates able to rapidly develop daptomycin non-susceptibility. To investigate assay reproducibility, 18 isolates were evaluated at three study sites. In addition, stability of daptomycin non-susceptibility was tested using repeated subculture without selective pressure. The impact of different media brands was also investigated. Results: Daptomycin non-susceptibility emerged in 12 of 23 species evaluated in this study (C. afermentans, amycolatum, aurimucosum, bovis, jeikeium, macginleyi, pseudodiphtheriticum, resistens, simulans, striatum, tuberculostearicum, and ulcerans) and was detected in 50 of 157 (31.8%) isolates tested. All isolates displayed low (susceptible) MIC values to vancomycin and telavancin before and after daptomycin exposure. Repeated subculture demonstrated 2 of 9 isolates (22.2%) exhibiting HLDR reverted to a susceptible phenotype. Of 30 isolates tested on three media brands, 13 (43.3%) had differences in daptomycin MIC values between brands. Conclusions: Multiple Corynebacterium species can rapidly develop daptomycin non-susceptibility, including HLDR, after a short daptomycin exposure period.

Treat Me Well or Will Resist: Uptake of Mobile Genetic Elements Determine the Resistome of Corynebacterium striatum

“…Initially, daptomycin resistance had been only reported in the genus of corynebacteria in C. jeikeium [ 6 ]; later isolates of daptomycin-resistant C. striatum were found [ 19 , 40 , 49 , 50 , 51 , 52 ]. Moreover, a recent study showed that several corynebacteria species could rapidly develop daptomycin non-susceptibility, including HLDR (high-level daptomycin resistance), after a short daptomycin exposure period [ 53 ].…”

Clinical Profile of Monomicrobial Corynebacterium Hip and Knee Periprosthetic Joint Infections

“…This has been chiefly described with C. striatum, where sequential clinical specimens from few reported cases exhibited emergence of HLDR during daptomycin therapy [ 23 , 25 , 26 ]. It was also demonstrated in vitro, where 90%–100% of C. striatum isolates developed HLDR after daptomycin exposure [ 23 , 27 ]. The emergence of HLDR has also been described in other species, including C. jeikeium and C. amycolatum [ 27 ].…”

“…It was also demonstrated in vitro, where 90%–100% of C. striatum isolates developed HLDR after daptomycin exposure [ 23 , 27 ]. The emergence of HLDR has also been described in other species, including C. jeikeium and C. amycolatum [ 27 ]. After 24 hours of in vitro daptomycin exposure, 12% of 119 non- striatum isolates developed HLDR [ 27 ].…”

“…The emergence of HLDR has also been described in other species, including C. jeikeium and C. amycolatum [ 27 ]. After 24 hours of in vitro daptomycin exposure, 12% of 119 non- striatum isolates developed HLDR [ 27 ]. The effect of this phenomenon on clinical outcomes remains unclear.…”

Corynebacterium striatum Bacteremia during SARS-CoV2 Infection: Case Report, Literature Review, and Clinical Considerations

“…Promising antibiotic alternatives may be represented by tigecycline or daptomycin [ 44 ]. Indeed, C. striatum seems to be susceptible to daptomycin, whether alone or combined with rifampicin [ 37 ]; despite the emergence of high-level daptomycin resistance has been already described [ 18 , 45 ]. In addition, high levels of resistance to a wide range of other antimicrobial drugs, including most β-lactams [ 11 ], macrolides [ 46 ], fluoroquinolones [ 47 ], aminoglycosides [ 48 ], and cotrimoxazole [ 3 ], have been reported.…”