FDA Approves Ceftobiprole Medocaril Sodium for 3 Indications

On April 3, 2024, the FDA approved ceftobiprole medocaril sodium for injection (Zevtera) for the treatment of Staphylococcus aureus bloodstream infections (SAB) and acute bacterial skin and skin structure infections (ABSSSI) in adults, as well as community-acquired bacterial pneumonia (CABP) in adult and pediatric patients.¹ Ceftobiprole is a cephalosporin antibiotic that provides an additional treatment option for these bacterial infections. Its safety and efficacy were evaluated in 4 clinical trials.^1,2

Staphylococcus aureus bacteria / nobeastsofierce - stock.adobe.com

Efficacy

Approval for SAB was evaluated through the phase 3 ERADICATE trial (NCT03138733) vs daptomycin. Patients (n = 390) were randomly assigned 1:1 to receive either drug. The primary outcome looked at overall treatment success, including survival, bacteremia clearance, symptom improvement, and no new bacterial complications. Ceftobiprole was noninferior to daptomycin for overall treatment success in SAB treatment (69.8% vs 68.7%, respectively).³

For ABSSSI approval, ceftobiprole was evaluated through the phase 3 TARGET study (NCT03137173) vs vancomycin plus aztreonam. Patients (n = 679) were randomly assigned 1:1 to receive ceftobiprole or vancomycin plus aztreonam for 5 to 14 days. The primary end point evaluated early clinical response 48 to 72 hours after treatment and investigator-assessed clinical success. Ceftobiprole was noninferior to vancomycin plus aztreonam for early clinical success rates and investigator-assessed clinical success in ABSSSI treatment (91.3% vs 88.1% and 90.1% vs 89.0%, respectively).⁴

Two phase 3 trials evaluated ceftobiprole for the CABP indication. In the adult study, 638 patients were randomly assigned 1:1 to ceftobiprole or ceftriaxone with or without linezolid for 5 to 14 days. The primary outcome was clinical cure rates, and the results showed the noninferiority of ceftobiprole compared to ceftriaxone with or without linezolid in treating CABP in adults (76.4% vs 79.3%, respectively).⁵

In the study for pediatric patients, 138 patients were randomly assigned 2:1 to receive ceftobiprole or a standard-of-care cephalosporin for 7 to 14 days. Early clinical response rates at day 4 were 95.7% and 93.2% for the ceftobiprole group and standard-of-care cephalosporin groups, respectively; clinical cure rates were 90.4% and 97.7%, respectively, demonstrating similar efficacy in both treatments for CABP in pediatric patients.⁶

Safety

Ceftobiprole has been associated with hypersensitivity reactions in clinical trials. Although rare (< 2%), it can be fatal and should be avoided in patients who have a known severe hypersensitivity to other cephalosporins. Common adverse reactions observed in more than 10% of the patients across the studies included anemia, nausea, and increased hepatic enzymes. Less common adverse effects that are more serious and led to discontinuation of treatment in the trials included vomiting, rash, and urticaria.²

Dosing and Administration

Ceftobiprole must be reconstituted with sterile water for injection or 5% dextrose solution before infusion. It is administered as a 667-mg intravenous (IV) dose every 6 hours on days 1 to 8 and every 8 hours thereafter for up to 42 days for SAB. For ABSSSI and CABP, dosing is 667 mg IV every 8 hours for 5 to 14 days. Each infusion should be administered over 2 hours at a concentration of 2.67 mg/mL. For treatment of CABP in pediatric patients, the dose is 20 mg/kg (max 667 mg/dose) every 8 hours administered at a concentration of 5.33 mg/mL for patients older than 3 months and younger than 12 years and at 13.3 mg/kg (max 667 mg/dose) every 8 hours for patients aged 12 to 18 years at a concentration of 2.67 mg/mL.

Ceftobiprole is renally dosed; decrease the dose in adult patients with a creatinine clearance less than 50 mL/min/1.73 m2 and pediatric patients with an eGFR less than 50 mL/min/1.73 m².²

Jenny Zhao, PharmD, is a PGY-1 pharmacy resident at UConn Health John Dempsey Hospital in Farmington, Connecticut.

Kevin Chamberlin, PharmD, FASCP, is the associate vice president and chief pharmacy officer at UConn Health John Dempsey Hospital in Farmington, Connecticut.

READ MORE: Infectious Diseases Resource Center

References

1. FDA approves new antibiotic for three different uses. News release. FDA. April 3, 2024. Accessed September 9, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibiotic-three-different-uses

2. Zevtera. Prescribing information. Basilea Pharmaceutica International Ltd; 2024. Accessed September 13, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218275s000lbl.pdf 

3. Holland TL, Cosgrove SE, Doernberg SB, et al; ERADICATE Study Group. Ceftobiprole for treatment of complicated Staphylococcus aureus bacteremia. N Engl J Med. 2023;389(15):1390-1401. doi:10.1056/NEJMoa2300220

4. Overcash JS, Kim C, Keech R, et al. Ceftobiprole compared with vancomycin plus aztreonam in the treatment of acute bacterial skin and skin structure infections: results of a phase 3, randomized, double-blind trial (TARGET). Clin Infect Dis. 2021;73(7):e1507-e1517. doi:10.1093/cid/ciaa974

5. Nicholson SC, Welte T, File TM Jr, et al. A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation. Int J Antimicrob Agents. 2012;39(3):240-246. doi:10.1016/j.ijantimicag.2011.11.005

6. Bosheva M, Gujabidze R, Károly É, et al. A phase 3, randomized, investigator-blinded trial comparing ceftobiprole with a standard-of-care cephalosporin, with or without vancomycin, for the treatment of pneumonia in pediatric patients. Pediatr Infect Dis J. 2021;40(6):e222-e229. doi:10.1097/INF.0000000000003077