Ceftobiprole: drug evaluation and place in therapy

Figures & data

Table 1. Ceftobiprole activity against clinical isolates of various bacterial species, from large surveillance studies.

Pathogen	MIC50 (mg/L)	MIC90 (mg/L)	Susceptible (%)^a	References
S. aureus	0.5	1 – 2	99.2 – 100	[12–17]
MRSA	1 – 2	2	96.5 – 100	[12–17]
CoNS	0.5 – 1	1 – 2	n. a. (>90 – 100)	[12–14,17]
MR-CoNS	1	1 – 4	n. a. (>90 – 100)	[12–15,17]
S. pneumoniae	≤0.06–0.25	0.06–0.5	99.3–99.8	[12–17]
β-hemolytic streptococci	≤0.06	≤0.06	n. a. (100)	[12–14]
viridans group streptococci E. faecalis	≤0.06 0.5	0.25 2-4	n. a. (>90 – 100) n. a. (95.9–100)	[12–15] [12–14]
H. influenzae	≤0.06	≤0.06–0.25	n. a. (>90 – 100)	[12–14,16]
M. catarrhalis	≤0.06–0.12	0.12 – >4	n. a. (>90 – 100)	[12–14,16]
Enterobacterales	≤0.06	16 – >16	73.8 – 87	[12–17]
P. aeruginosa	2 – 4	8 – >16	n. a. (61.8–86)	[12–18]

CoNS, coagulase-negative staphylococci; MIC, minimum inhibitory concentration; MR-CoNS, methicillin-resistant CoNS; MRSA, methicillin-resistant Staphylococcus aureus.

^asusceptibility rates calculated according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints, version 9.0, 2019 (www.eucast.org), from references where the value was reported or could be calculated from the reported MIC data; n.a., not applicable, due to the lack of clinical breakpoints. Values in parentheses are susceptibility rates considering the EUCAST PK/PD breakpoint for susceptibility of 4 mg/L (www.eucast.org).

Table 2. Pharmacokinetic (PK) parameters of ceftobiprole after single 500 mg intravenous dose over 2 h infusion in healthy volunteers [25,29].

PK parameter
Cmax (mg/L)	29.2 ± 5.52
Protein binding (%)	16.0
Vd (L)	21.7 ± 3.3
t1/2 (h)	3.1 ± 0.3
AUC0-∞ (mg⋅h/L)	104.0 ± 13.9
CLT (L/h)	4.89 ± 0.69
CLR (L/h)	4.08 ± 0.72
Urinary excretion (%)	83.1 ± 9.1

Table 3. Efficacy data from phase 3, non-inferiority, randomized clinical trials in patients with CAP and HAP/VAP.

Study	Reference	Investigational drugs (dosage)	Comparator/s (dosage)	Primary endpoint	Study population	Cure rates (cured/treated)	% difference (95% CI)
CAP, 2012	[38]	Ceftobiprole (500 mg q8h)	Ceftriaxone* (2 g q24h)	Clinical cure (either resolution of signs and symptoms of infection or sufficient improvement rendering continuation of antibacterial therapy unnecessary)	CAP ITT population Ceftobiprole Ceftriaxone CE population Ceftobiprole Ceftriaxone	76.4% (240/314) 79.3% (257/324) 86.6% (200/231) 87.4% (208/238)	−2.9 (−9.3 to +3.6) Reference -0.8 (−6.9 to +5.3) Reference
HAP/VAP, 2014	[37]	Ceftobiprole (500 mg q8h)	Ceftazidime (2 g q8h) plus Linezolid (600 mg q 12h)	Clinical cure (either resolution of signs and symptoms of infection or sufficient improvement rendering continuation of antibacterial therapy unnecessary)	HAP excluding VAP ITT population Ceftobiprole Ceftazidime plus linezolid CE population Ceftobiprole Ceftazidime plus linezolid VAP ITT population Ceftobiprole Ceftazidime plus linezolid CE population Ceftobiprole Ceftazidime plus linezolid	59.6% (171/287) 58.8% (167/284) 77.8% (154/198) 76.2% (141/185) 23.1% (24/104) 36.8% (39/106) 37.7% (20/53) 55.9% (33/59)	+0.8 (−7.3 to +8.8) Reference +1.6 (−6.9 to +10.0) Reference -13.7 (−26.0 to −1.0) Reference -18.2 (−36.4 to +0.0) Reference

CAP, community-acquired pneumonia; CE, clinically evaluable; HAP, hospital-acquired pneumonia; ITT, intention-to-teat; VAP, ventilator-associated pneumonia.

*plus optional linezolid

Figure 1. Algorithm illustrating the possible use of ceftobiprole for empirical therapy in patients with CAP and HAP (non-VAP).

CAP, community-acquired pneumonia; ESBL, extended-spectrum β-lactamases; HAP, hospital-acquired pneumonia; MRSA, methicillin-resistant Staphylococcus aureus; VAP, ventilator-associated pneumonia.

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