CEFTOBIPROLE INJ,PWDR

Clinical Criteria Summary

FDA approved for patients aged 18 years and over
Staphylococcus aureus bloodstream infection (SAB), including right-sided infective endocarditis caused by MSSA and MRSA
Acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of MSSA, MRSA, Streptococcus pyogenes, and Klebsiella pneumoniae
Community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of MSSA, MRSA, S. pneumoniae, H. flu, H. parainfluenzae, E. coli, and K. pneumoniae

Dose: 667 mg IV (CFB medocaril 667 mg is equivalent to CFB 500 mg)
SAB: Q6h on days 1 to 8, then Q8H from day 9
ABSSSI and CABP: Q8H
Infusion time: 2 hours
Renal dose adjustments required for CrCl <50 ml/min and >150 ml/min
Reconstitution: Lyophilized powder requires reconstitution with sterile water for injection or 5% dextrose injection; shake vigorously until dissolution (up to 10 minutes) then dilute in 250 mL bag of 0.9% sodium chloride (NS) or 5% dextrose in water (D5W)
Storage: Reconstituted infusion stored at room temperature for 6 hours (D5W) or 4 hours (NS), or refrigerated for 94 hours (D5W) or 24 hours (NS)
Must not be mixed or co-administered with calcium-containing solutions

Demonstrated non-inferiority to comparators in Phase 3 randomized, double-blinded trials for SAB, ABSSSI, and CABP per FDA definitions
SAB: Non-inferior to daptomycin +/- aztreonam; superiority not achieved; overall treatment success 69.8% vs 68.7%; microbiologic eradication 82% vs 77%
ABSSSI: Non-inferior to vancomycin +/- aztreonam for early clinical response and clinical cure at test of cure (TOC); superior to vancomycin group in clinically evaluable population for primary endpoint
CABP: Non-inferior to ceftriaxone +/- linezolid for clinical cure rate and microbiological eradication rate at TOC
Not approved for ventilator-associated bacterial pneumonia (VABP) due to increased mortality observed in trials

Contraindicated in patients with known hypersensitivity to components of CFB or other members of the cephalosporin class
Boxed warnings: None
Warnings/Precautions: Increased mortality with unapproved use in VABP; neurotoxicity including seizures and encephalopathy possible across cephalosporin generations
Discontinue CFB if seizures or other adverse CNS reactions occur
Common adverse reactions: Anemia, nausea, hypokalemia, vomiting, hepatic enzyme and bilirubin increased, diarrhea, blood creatinine increased, hypertension, leukopenia, pyrexia
Serious adverse events/deaths/discontinuation: Increased mortality in VABP patients, serious hypersensitivity and skin reactions, seizures and other CNS reactions, C. difficile associated diarrhea
Thrombosis: Increased frequency observed in CFB arm vs daptomycin arm (5.2% vs 2%) in ERADICATE trial; overall less likely given confounding factors; monitored via post-market surveillance

Limited role for pneumonia (CAP/HAP) and SSTI due to numerous potential treatment options
SAB: Treatment options limited, particularly for MRSA bacteremia; vancomycin requires therapeutic drug monitoring and can cause renal insufficiency; daptomycin commonly used; ceftaroline used commonly despite lack of RCTs/FDA indication for this use; linezolid has limited data for complicated bacteremia and long-term myelosuppression risk
CFB supports better understanding of optimal dosing due to RCT data compared to ceftaroline
Disadvantages include frequency of dosing (especially for SAB) and limited stability, which may limit use as a second-line agent for SAB
Use should involve local ID experts and Antimicrobial Stewardship Champions to ensure appropriate use given complexities of drug, dosing, and spectrum
ABSSSI: Single treatment option combining MRSA and gram-negative coverage may be useful in certain clinical settings
CABP: Important limitation is coverage of ESBL & Acinetobacter and dosing schedule (667mg IV Q8H); monotherapy may simplify initial empirical treatment relative to combination therapies
MSSA SAB/RIE: Treatment includes cefazolin, nafcillin, oxacillin, and DAP; vancomycin can be used in patients with beta-lactam allergy or those who cannot receive other drugs

Pregnancy: No clinical data available; not associated with adverse developmental effects in rats or rabbits at doses clinically equivalent to MHRD
Lactation: Detected in rat milk; no data on presence in human milk, effects on breastfed infant, or effects on milk production; no concerns for serious adverse reactions in breastfed infant; risk/benefit discussion recommended

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