Table 1.
Single-dose pharmacokinetic parameters and EUCAST clinical breakpoints for ceftobiprole and other cephalosporins
| Parameter | Ceftobiprole 500 mg [15, 24, 26] | Ceftazidime 1000 mg [27, 33, 67] | Ceftriaxone 500 mg [28, 40] | Ceftaroline 600 mg [30, 32] | Cefotaxime 500 mg [31, 35, 74] | Cefepime 500 mg [29, 34] |
|---|---|---|---|---|---|---|
| Pharmacokinetic parameters following single-dose administration in healthy individuals | ||||||
| Number of patients | 28 | 15a | 12 | 6b | 9 | |
| Infusion time (min) | 120 | 30 | 30 | 60 | 5 | 30 |
| C max (mg/L) | 29.2 ± 5.52 | 86.29 ± 13.06 | 82.0 ± 10.4 | 28.4 ± 7.0 | 37.9 ± 2.1 | 31.9 ± 6.0 |
| t max (h) | – | – | 0.5 | 1.0 | – | – |
| AUC∞ (mg·h/L) | 104 ± 13.9 | 150.30 ± 19.84 | 551 ± 91 | 75.6 ± 9.7 | 30.6 ± 2.2 | 56.6 ± 11.4 |
| t ½ for the distribution phase (h) | – | – | 0.21c | – | 0.19 ± 0.03 | – |
| t ½ for the post-distribution phase (h) | 3.1 ± 0.3 | 1.95 + 0.25 | 6.30c | 2.9 ± 0.4 | 1.04 ± 0.07 | 2.00 ± 0.64 |
| V d | 21.7 ± 3.3 L | 0.21 ± 0.03 L/kg | 8.46 ± 1.11 L | 29.3 ± 5.2 Ld | 19.1 ± 1.2 L/1.73 m2 | 18.3 ± 1.9 L |
| CLT | 4.89 ± 0.69 L/h | 0.095 ± 0.014 L/h/kg | 0.929 ± 0.15 L/h | 7.11 ± 0.89 L/he | 14.72 ± 1.17 L/h/1.73 m2 | 9.12 ± 1.68 L/h |
| CLR | 4.08 ± 0.72 L/h | 0.084 ± 0.014 L/h/kg | 0.373 ± 0.60 L/h | 3.36 ± 0.83 L/h | 8.81 ± 1.12 L/h/1.73 m2 | 8.28 ± 1.98 L/h |
| Urinary excretion (%)f | 83.1 ± 9.06 | 88.26 ± 5.50 | 38 ± 7g [28] (~60 %) [42] |
46.8 ± 6.1 | 58.8 | 91.0 ± 15.2 |
| Protein binding (%) | 16 | 10–23 | 41–99 | ~20 | 37 | ~20 |
| EUCAST MIC breakpoints (S≤/R>) [75] | ||||||
| Staphylococcus aureus | 2/2 | ND | NDh | 1/1 | NDh | NDh |
| Streptococcus pneumoniae | 0.5/0.5 | ND | 0.5/2 | 0.25/0.25 | 0.5/2 | 1/2 |
| Enterobacteriaceae | 0.25/0.25 | 1/4 | 1/2 | 0.5/0.5 | 1/2 | 1/4 |
| Pseudomonas aeruginosa | IE | 8 | ND | ND | ND | 8 |
Data are expressed as mean ± standard deviation or mean ± standard error (cefotaxime), except for t max, which is expressed as median
AUC ∞ area under the plasma concentration–time curve from time zero extrapolated to infinity, C max maximum plasma concentration, CL CR creatinine clearance, CL R renal clearance, CL T total systemic clearance, EUCAST European Committee on Antimicrobial Susceptibility Testing, F m fraction of the dose metabolized, IE insufficient evidence, MIC minimum inhibitory concentration, ND breakpoint not defined (susceptibility testing not recommended), R resistant, S susceptible, t ½ half-life, t max time to C max, V d volume of distribution, V z volume of distribution based on the terminal phase
aMean weight 72.0 kg
bIndividuals with normal renal function (CLCR > 80 mL/min)
cHarmonic mean
d V z/F m, volume of distribution based on the terminal phase/fraction of the dose metabolized
eCL/Fm, plasma clearance/fraction of the dose metabolized
fUnchanged drug over 24 h
g n = 11
hSusceptibility can be inferred from cefoxitin testing (S ≤/R>, >4 mg/L)