In vitro pharmacodynamic study of ceftobiprole, vancomycin, linezolid and daptomycin against staphylococcal bloodstream infections / 中华传染病杂志

ABSTRACT

Objective:To evaluate the antibacterial efficacy of ceftobiprole, vancomycin, linezolid, and daptomycin against Staphylococcus aureus (SAU) and coagulase-negative Staphylococcus (CNS) bloodstream infections, which can provide a reference for clinical medication. Methods:A total of 1 777 strains of staphylococci were isolated from blood culture of 51 hospitals within the Blood Bacterial Resistant Investigation Collaborative System (BRICS) from January to December in 2021. The dilution method was used to assess the minimum inhibitory concentrations (MIC) of ceftobiprole, vancomycin, linezolid and daptomycin on staphylococci. Additionally, the probability of target attainment (PTA) and cumulative fraction of response (CFR) of these medications in varied dosage regimens were predicted using Monte Carlo simulation.Results:Ceftobiprole demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus(MRSA), the MIC 50 and MIC 90 were 0.500 and 1.000 mg/L, respectively, and the MIC range was ≤0.060 to 4.000 mg/L.Meanwhile, the ceftobiprole-resistance rate of SAU was 0.1%(1/1 073), but the resistance rate of CNS was 7.7%(54/704). There was no evidence of staphylococcal resistance to daptomycin or vancomycin. Against methicillin-sensitive Staphylococcus aureus (MSSA), no resistance to the four drugs was observed. Monte Carlo simulation showed that standard drug regimens of ceftobiprole (500 mg once every eight hours) and daptomycin (6 mg·kg -1·d -1) achieved high PTA and CFR against staphylococcus.The current vancomycin and linezolid standard treatment for staphylococcal bloodstream infections had a low CFR. When vancomycin 1 000 mg once every eight hours was used, the CFRs of MRSA and MSSA were both≥90.0%, while the CFR of CNS was still less than 80.0%. CFR of linezolid against staphylococcus was ≥90.0% under the dosages of 600 mg once every eight hours. Conclusions:Ceftobiprole, vancomycin, linezolid and daptomycin all show strong antibacterial activity against staphylococcus.Ceftobiprole and daptomycin standard treatment represent adequate antibacterial efficacy against staphylococcal bloodstream infections. Furthermore, appropriate increase of the dosages of vancomycin and linezolid based on the MIC value and species of bacteria is necessary.