Scientific Reports - Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection

Ceftobiprole demonstrated noninferiority to daptomycin for the treatment of Staphylococcus aureus bacteraemia. A range of post hoc exploratory analyses were undertaken to better inform additional key ...

Staphylococcus aureus continues to represent a significant cause of infection worldwide, with elevated morbidity and mortality rates. S. aureus is a leading cause of both community-acquired and health...

Innoviva Specialty Therapeutics’ antibiotic is the first and only FDA-approved cephalosporin indicated to treat Staphylococcus aureus bacteremia (SAB), including right-sided endocarditis, caused by th...

ABSTRACTDespite the use of recommended treatments against Enterococcus faecalis infective endocarditis, mortality rates remain at 30%. Penicillin-resistant, ampicillin-susceptible E. faecalis (PRASEF) has been associated with worsened clinical outcomes; however, a more common phenotype, borderline-PRASEF (penicillin minimum inhibitory concentration [MIC] 4–8 µg/mL), decreases the activity of ampicillin-ceftriaxone in vitro. Ceftobiprole presents a promising alternative against borderline-PRASEF and also has shown activity against vancomycin-resistant E. faecalis (VREfs). The ceftobiprole MIC distribution was determined via broth microdilution for 78 E. faecalis clinical blood isolates, including 71 borderline-PRASEF. Ceftobiprole activity alone was compared to ampicillin-ceftriaxone via in vitro 24-hour time-kill assays against 30 E. faecalis isolates, 24 of which were borderline-PRASEF and 15 were VREfs. Ceftobiprole and ceftriaxone were tested at physiologic concentrations (fCpss 13.9 µg/mL and 17.2 mcg/mL, respectively) and ampicillin at subinhibitory concentrations (0.25 × MIC and 0.5 × MIC). Isolates where ceftobiprole alone had limited activity were tested against ceftobiprole-ampicillin. Ceftobiprole maintained activity against borderline-PRASEF compared to ampicillin-ceftriaxone. Ceftobiprole also demonstrated more activity against VREfs isolates and isolates with an elevated ceftobiprole MIC ≥16 µg/mL, compared to ampicillin-ceftriaxone. Ceftobiprole did not achieve ≥2 log10 CFU/mL kill in six isolates but was able to achieve this once combined with ampicillin. When tested at ampicillin inhibitory concentrations, ceftobiprole-ampicillin activity trended towards antagonism in two isolates. Overall, ceftobiprole alone had greater activity compared to ampicillin-ceftriaxone, and there may be a potential role of ceftobiprole combination therapy in certain isolates.

European Journal of Clinical Microbiology & Infectious Diseases - This study evaluates the in vitro activity of five clinically-relevant β-lactam antibiotics against 158 Enterococcus...

Zevtera, an advanced-generation cephalosporin, is available for treating Staphylococcus aureus bacteremia and 2 other types of bacterial infection.

ABSTRACTCeftobiprole is an advanced-generation cephalosporin active against methicillin-resistant Staphylococcus aureus and other clinically relevant bacteria. Ceftobiprole was recently (April 2024) approved for clinical use in the United States, but susceptibility testing is still not available on commercial automated susceptibility testing systems. We evaluated the accuracy and error rates when using susceptibility to ceftaroline to predict susceptibility to ceftobiprole. A total of 42,363 clinical isolates were collected through the SENTRY Antimicrobial Surveillance Program from 34 US medical centers in 2016–2020 and tested against ceftobiprole and ceftaroline by broth microdilution method. The accuracy of the surrogate test (susceptibility to ceftaroline) was defined as the percentage of isolates susceptible to ceftobiprole among ceftaroline-susceptible isolates. Minor error rate was then defined as the percentage of ceftobiprole-intermediate among ceftaroline-susceptible isolates, and very major error was defined as the percentage of ceftobiprole-resistant isolates among ceftaroline-susceptible isolates. The accuracy of the surrogate test to predict susceptibility to ceftobiprole was >99% for S. aureus (99.98%), including methicillin-resistant S. aureus (99.95%), Streptococcus pneumoniae (99.48%), β-hemolytic streptococci (100.00%), Escherichia coli (99.97%), and Klebsiella pneumoniae (99.91%). Accuracy was also extremely high for Haemophilus spp. (98.86%) and Enterobacterales (98.73%). Minor error rates were <1% for all organism groups evaluated, and very major errors were only observed with S. pneumoniae (0.06%), Haemophilus spp. (0.31%), Enterobacterales (0.40%), and K. pneumoniae (0.03%). In conclusion, the results of the comparative analyses of ceftobiprole and ceftaroline MIC values show that susceptibility to ceftobiprole can be inferred by susceptibility to ceftaroline with very high accuracy.IMPORTANCECeftobiprole was recently (April 2024) approved for clinical use in the United States but susceptibility testing is still not available on commercial automated susceptibility testing systems and may not be available for some time. In the interim, one possible strategy to assess ceftobiprole susceptibility would be to apply the susceptibility results of ceftaroline as a surrogate marker of susceptibility. This strategy could facilitate rapid clinical use of ceftobiprole in the United States pending the more necessary availability of commercial susceptibility testing devices to direct testing ceftobiprole.

Scientific Reports - Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection

Despite modest progress, Staphylococcus aureus bloodstream infections—particularly those caused by MRSA—remain a major cause of morbidity and mortality, underscoring the urgent need for novel, broad-s...

Innoviva Specialty Therapeutics announces the U.S. commercial launch of ZEVTERA® (ceftobiprole), an advanced-generation cephalosporin antibiotic. ZEVTERA is the first and only FDA-approved cephalosporin for treating three types of bacterial infections, including Staphylococcus aureus bacteremia (SAB) with right-sided endocarditis caused by MRSA. The drug demonstrated non-inferiority to daptomycin in Phase 3 ERADICATE study, with success rates of 69.8% vs 68.7%. ZEVTERA received Priority Review, Fast Track, and Qualified Infectious Disease Product designations. This marks Innoviva's second novel therapy launch in two years targeting drug-resistant pathogens. The drug addresses a significant medical need, as over 100,000 people in the U.S. experience bacteremia annually, with nearly 20,000 deaths. Innoviva acquired exclusive U.S. marketing rights from Basilea Pharmaceutica in December 2024.