| Summary: | Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) in China. We found that MRSA, methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA), and methicillin-susceptible coagulase-negative <i>Staphylococcus</i> (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole’s MIC<sub>50/90</sub> value against <i>Enterococcus faecalis</i> was 0.25/2 mg/L, whereas <i>Enterococcus faecium</i> was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative <i>Enterobacterales</i>, excluding <i>Klebsiella oxytoca</i>, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC<sub>50/90</sub> value of ceftobiprole against <i>Pseudomonas aeruginosa</i> was 2/16 mg/L, and for <i>Acinetobacter baumannii</i>, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative <i>Enterobacterales</i> and <i>Pseudomonas aeruginosa</i> (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive <i>Enterobacterales</i> and <i>Acinetobacter baumannii</i>. These results provide important information to clinicians.
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