ATCvet code: QJ01DD91
Pharmacodynamics
Cefovecin is a third-generation cephalosporin with a broad-spectrum of activity against Gram-positive and Gram-negative bacteria. It differs from other cephalosporins in that it is highly protein bound and has a long duration of activity. As with all cephalosporins, the action of cefovecin results from the inhibition of bacterial cell wall synthesis; cefovecin has bactericidal activity.
Cefovecin exhibits in vitro activity against Staphylococcus pseudintermedius and Pasteurella multocida which are associated with canine and feline skin and soft tissue infections (SSTI). Anaerobic bacteria such as Bacteroides spp. and Fusobacterium spp. collected from feline abscesses were shown to be susceptible. Porphyromonas gingivalis and Prevotella intermedia collected from canine periodontal disease were also shown to be susceptible. In addition, cefovecin exhibits in vitro activity against Escherichia coli which is associated with canine and feline urinary tract infections (UTI).
In vitro activity against these pathogens as well as against other skin and urinary tract pathogens collected during a European (Belgium, Czech Republic, Hungary, The Netherlands, Poland, Spain, Switzerland, Sweden, France, Germany, Italy and United Kingdom) MIC survey (2017-2018).
Bacterial Pathogen | Origin | No. of Isolates | cefovecin MIC (mcg/ml) | 2024 cefovecin CLSI clinical breakpoints (mcg/ml) |
MIC50 | MIC90 | Susceptible | Intermediate | Resistant |
Staphylococcus intermedius group (SSTI) | Dog Cat | 440 24 | 0.12 0.12 | 16 >32 | ≤0.5 NA | 1 NA | ≥2 NA |
β-haemolytic Streptococci (SSTI) | Dog Cat | 121 18 | ≤0.015 ≤0.015 | 0.03 ≤0.015 | ≤0.12 NA | 0.25 NA | ≥0.5 NA |
Escherichia coli (UTI) | Dog Cat | 333 183 | 1 1 | 2 2 | ≤2 ≤2 | 4 4 | ≥8 ≥8 |
Escherichia coli (SSTI) | Dog | 112 | 0.5 | 2 | NA | NA | NA |
Pasteurella spp. (SSTI) | Dog Cat | 26 69 | ≤0.015 0.03 | 0.12 0.03 | NA ≤0.12 | NA 0.25 | NA 0.5 |
Proteus spp. (UTI) | Dog | 101 | 0.25 | 0.5 | ≤2 | 4 | ≥8 |
Bacteroides spp. | Cat | 23 | 0.5 | 16 | NA | NA | NA |
NA: not available
Resistance to cephalosporins results from enzymatic inactivation (β-lactamase production), from reduced permeability by porin mutations or change in efflux, or by selection of low-affinity penicillin-binding proteins. Resistance may be chromosomal or plasmid-encoded and may be transferred if associated with transposons or plasmids (see also section 'Special warnings').
When applying the CLSI clinical breakpoints, the observed resistance levels for canine E. coli and Proteus mirabilis UTI isolates were 4.5 and 0.0% respectively. The observed resistance levels for canine β-haemolytic streptococci and the S. intermedius group SSTI isolates were 0.0 and 15.2% respectively. The observed resistance levels for feline E. coli UTI isolates and for feline Pasteurella multocida SSTI isolates were 6.0% and 0.0% respectively.
Pseudomonas spp. and Enterococcus spp. isolates are inherently resistant to cefovecin.
Pharmacokinetics
Cefovecin has unique pharmacokinetic properties with extremely long elimination half-lives in both dogs and cats.
In dogs, when cefovecin was administered as a single subcutaneous dose of 8 mg/kg body weight, absorption was rapid and extensive; peak plasma concentration at 6 hours was 120 mcg/ml and bioavailability approximately 99 %. Peak concentrations in tissue cage fluid of 31.9 mcg/ml were measured 2 days after administration. Fourteen days after administration, the mean cefovecin concentration in plasma was 5.6 mcg/ml. Plasma protein binding is high (96.0 % to 98.7 %) and the volume of distribution is low (0.1 l/kg). Elimination half-life is long – approximately 5.5 days. Cefovecin is primarily eliminated unchanged via the kidneys. At fourteen days after administration, urine concentrations were 2.9 mcg/ml.
In cats, when cefovecin was administered as a single subcutaneous dose of 8 mg/kg body weight, absorption was rapid and extensive; peak plasma concentration at 2 hours was 141 mcg/ml and bioavailability approximately 99 %. Fourteen days after administration the mean cefovecin concentration in plasma was 18 mcg/ml. Plasma protein binding is high (more than 99 %) and the volume of distribution is low (0.09 l/kg). Elimination half-life is long – approximately 6.9 days. Cefovecin is primarily eliminated unchanged via the kidneys. At ten and fourteen days after administration, urine concentrations were 1.3 mcg/ml and 0.7 mcg/ml, respectively. Following repeated administrations at the recommended dose, elevated concentrations of cefovecin were observed in plasma.