A systematic review evaluating the pharmacokinetics (PK) and PK/pharmacodynamic (PD) profiles of ceftaroline and ceftobiprole (fifth-generation cephalosporins) for *S. aureus* infections, including special populations such as critically ill patients and those with deep-seated infections.
Standard dosing achieved adequate PK/PD target attainment (bacteriostasis, 1-log₁₀ and 2-log₁₀ kill) in non-severe infections (% fT>MIC targets: 20%, 26%, 37% for ceftaroline; 8.8%, 13.5%, 23% for ceftobiprole); however, critically ill patients showed high PK variability with increased volumes of distribution, often requiring intensified doses and prolonged infusions to reach stringent targets (e.g., 100% fT>MIC).
- Included studies are heterogeneous in design and patient populations, limiting direct comparisons. - PK/PD targets used are pre-clinical and may not fully translate to clinical cure endpoints. - Tissue penetration data for deep-seated infections are limited across both agents.
For critically ill patients or those with deep-seated *S. aureus* infections, standard ceftaroline or ceftobiprole dosing may be insufficient — consider intensified dosing regimens and prolonged infusions to reliably achieve PK/PD targets. Therapeutic drug monitoring should be considered where feasible in high-risk patients.
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