Antimicrobial activity of ceftobiprole and comparator agents when tested against gram-positive and -negative organisms collected across China (2016–2018)

Abstract

Background Ceftobiprole is a fifth-generation cephalosporin which has been reported to have broad antibacterial spectrum when tested against bacteria collected from other countries except China. This study evaluated the in vitro activity of ceftobiprole in comparison with other comparators against clinically significant isolates collected across from China. Results Susceptibility testing of ceftobiprole and comparators against 1163 clinically isolated Gram-positive and Gram-negative bacteria was performed with broth micro dilution method following the CLSI guidelines. All 110 S. aureus were susceptible to ceftobiprole with MIC50/90 of 1/2 mg/L for MRSA and 0.5/1 mg/L for MSSA. For Coagulase-negative staphylococci (CNS), MIC50/90 of ceftobiprole for MRCNS and MSCNS was 1/2 mg/L and 0.25/0.5 mg/L. Ceftobiprole demonstrated good potency against E. faecalis (MIC50/90 of 0.5/1 mg/L) but limited activity against E. faecium (MIC50/90 of > 32/ > 32 mg/L). Ceftobiprole demonstrated potent activity against all 39 β-hemolytic Streptococcus spp. with MIC50/90 ≤ 0.015/ ≤ 0.015–2 mg/L and 110 of PSSP with 98.2% susceptibility. Ceftobiprole inhibited all isolates of H. influenzae and M. catarrhalis at ≤ 1 mg/L. 91.8% and 98.2% of the ESBL-negative E. coli and K. pneumoniae were susceptible to ceftobiprole, but most of the ESBL-positive or carbapenem-resistant strains were also resistant to ceftobiprole. Ceftobiprole inhibited 84.2% of carbapenem-susceptible P. aeruginosa and 94.1% of carbapenem-susceptible A. baumannii at ≤ 8 mg/L, but only 52.6% of carbapenem-resistant P. aeruginosa and 5.3% of carbapenem-resistant A. baumannii. Conclusion Ceftobiprole demonstrated good in vitro activity against a broad range of clinically relevant contemporary Gram-positive and Gram-negative bacterial isolates.

In Vitro Antibacterial Activity of Ceftobiprole and Comparator Compounds against Nation-Wide Bloodstream Isolates and Different Sequence Types of MRSA

“…In this study, we demonstrated that ceftobiprole displays potent in vitro activity against E. faecalis, with MIC 50/90 values of 0.25/2 mg/L, but not against E. faecium. These data are consistent with a study by Yin et al, who reported ceftobiprole MIC 50/90 values against E. faecalis and E. faecium of 0.5/1 mg/L and 32/>32 mg/L, respectively [12]. The antibacterial activity of ceftobiprole against E. faecalis is mediated by the inhibition of peptidoglycan cross-linking by the acylation of serine at the active sites of penicillin-binding proteins (PBPs) with a greater affinity for PBP4 [27].…”

“…Despite this, we identified some MRSA, MSCNS, and MRCNS strains that were resistant to ceftobiprole. These findings are consistent with studies conducted in Europe and China [11][12][13]. For example, Amsler et al reported the in vitro antibacterial activity of ceftobiprole in the United States, with MIC 50/90 values of 0.5/2 mg/L, 0.25/0.5 mg/L, 0.5/2 mg/L, and 0.25/0.5 mg/L against MRSA, MSSA, MRCNS, and MSCNS, respectively, and Yin et al identified values 1/2 mg/L, 0.5/1 mg/L, 1/2 mg/L, and 0.25/0.5 mg/L in a study conducted in China, respectively.…”

“…Ceftobiprole possesses antibacterial activity against ESBL-negative Enterobacterales (except for K. oxytoca), E. cloacae, Salmonella spp., and S. marcescens, similar to that of ceftriaxone, ceftazidime, and cefepime, but slightly inferior to carbapenems, such as ertapenem. These findings are consistent with other studies conducted in China and Europe [12,20]. A large-sample study by Pfaller et al demonstrated sensitivity rates of Enterobacterales to ceftobiprole, ceftriaxone, ceftazidime, cefepime, and imipenem of 73.8%, 73.3%, 74.2%, 78.2%, and 96.3%, respectively.…”

In Vitro Activities of Ceftobiprole, Dalbavancin, Tedizolid and Comparators against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus Associated with Skin and Soft Tissue Infections

“…Similar high susceptibility rates (99.3%) of ceftobiprole against recent European MRSA isolates were recently reported [45]. Likewise, the ceftobiprole in vitro potency has been demonstrated in several previous studies of globally sourced MRSA isolates [46,47]. Moreover, the clinical efficacy of ceftobiprole was shown to be comparable to that of vancomycin and vancomycin plus ceftazidime in the treatment of cSSTIs in two earlier phase III clinical trials (STRAUSS I and STRAUSS II) [48].…”