Ceftobiprole

Uses

Broad spectrum antibiotic.

Definition

ChEBI: Ceftobiprole is a fifth-generation cephalosporin antibiotic having (E)-[(3'R)-2-oxo[1,3'-bipyrrolidin]-3-ylidene]methyl and [(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(hydroxyimino)acetyl]amino side groups located at positions 3 and 7 respectively; developed for the treatment of hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia, VAP) and community-acquired pneumonia (CAP). It has a role as an antimicrobial agent. It is a cephalosporin and a member of thiadiazoles.

Antimicrobial activity

The most important property distinguishing it from older cephalosporins is activity against methicillin-resistant staphylococci, a property conferred by a high affinity for penicillinbinding protein 2′ (2a). MICs for methicillin-resistant strains are nevertheless somewhat higher than those seen with fully susceptible strains. A similar situation exists with coagulasenegative staphylococci and with Str. pneumoniae, for which strains with reduced susceptibility to penicillin are less susceptible than fully resistant strains, while remaining within therapeutically achievable levels.
Otherwise activity approximates to that of cephalosporins of group 4 . Activity against Ps. aeruginosa is modest and much reduced against ceftazidime-resistant strains.

Acquired resistance

It is hydrolyzed by extended spectrum β-lactamases of enterobacteria , which are therefore resistant. The prospects for the emergence of resistance during extensive clinical use are presently unclear, though increased resistance in Staph. aureus appears to be difficult to induce under laboratory conditions.

Pharmacokinetics

C_{max 500 mg (667 mg prodrug): c. 35 mg/L end infusion
intravenous (30-min infusion)
Plasma half-life: c. 3 h
Volume of distribution: 18.4 L
Plasma protein binding: 16%
The prodrug is rapidly hydrolyzed in plasma to release the active form together with diacetyl (2,3-butanediol) and CO2. Distribution approximates to the extracellular fluid volume in adults. There is no accumulation on repeat dosing in subjects with normal renal function.
It is chiefly excreted in urine by glomerular filtration. A urinary concentration exceeding 1 g/L is achieved within the first 2 h of a 500 mg (active drug equivalent) dose and 80–90% of active drug can be recovered within 24 h.}

Clinical Use

Ceftobiprole can be used as Broad spectrum antibiotic and in complicated infections of skin and skin structures.

Side effects

Limited studies have so far revealed no unexpected side effects. Nausea, vomiting and altered taste sensation appear to be the most common.

Raw materials

Preparation Products