Pharmacotherapeutic group: Anti-infectives for systemic use, lincosamides. ATCvet code: QJ01FF01
Clindamycin is a semi-synthetic antibiotic produced by 7(S)-chloro substitution of the 7(R)-hydroxy group of the natural antibiotic produced by Streptomyces lincolnensis var. lincolnensis.
Clindamycin acts by a bacteriostatic mechanism where the drug interferes with protein synthesis within the bacterial cell, thus inhibiting the growth and multiplication of the bacteria. Clindamycin binds to the 23S ribosomal RNA component of the 50S subunit. This prevents amino acids binding on these ribosomes, and therefore inhibits peptide bond formation.The ribosomal sites are close to those bound by macrolides, streptogramins or chloramphenicol.
Clindamycin is a moderate spectrum antimicrobial drug.
Clindamycin has in vitro activity against the following micro-organisms (see the following MICs):
•Aerobic Gram-positive cocci, including: Staphylococcus aureus and Staphylococcus pseudintermedius (penicillinase and non-penicillinase producing strains), Streptococcus spp. (except Streptococcus faecalis).
•Anaerobic Gram-negative bacilli, including: Bacteroides spp., Fusobacterium necrophorum.
•Clostridia: Most Clostridium perfringens are susceptible.
CLSI clindamycin veterinary breakpoints are available for dogs in Staphylococcus spp. and Streptococci-β-haemolytic group in skin and soft tissue infections: S ≤0.5 μg/ml; I =1-2 μg/ml; R ≥4 μg/ml (CSLI July 2013).
Type and mechanism of resistance:
Clindamycin belongs to the lincosamide group of antibiotics. Resistance can develop to the lincosamides alone, but more commonly cross-resistance occurs among macrolides, lincosamides and streptogramin B antibiotics (MLSB group). Resistance is the result of methylation of adenine residues in the 23S RNA of the 50S ribosomal subunit, which prevents drug binding to the target site. Different bacterial species are able to synthesize an enzyme, encoded by a series of structurally related erythromycin ribosomal methylase (erm) genes. In pathogenic bacteria, these determinants are mostly borne by plasmids and transposons that are self-transferable. The erm genes occur predominantly as variants erm(A) and erm(C) in Staphylococcus aureus and as variant erm(B) in Staphylococcus pseudintermedius, streptococci and enterococci . Bacteria resistant to macrolides but initially susceptible to clindamycin, rapidly develop resistance to clindamycin when exposed to macrolides. These bacteria present a risk of in vivo selection of constitutive mutants.
MLSB inducible resistance is not detected by standard in vitro susceptibility testing methods. The CLSI recommends the D-zone test to be routinely performed in veterinary diagnostic laboratories in order to detect clinical isolates with inducible resistance phenotype. Clindamycin use should be discouraged in these patients.
The incidence of resistance to lincosamides in Staphylococcus spp. appears to be wide-ranging in Europe. Literature data (2016) report an incidence between 25 to 40%.
Clindamycin hydrochloride is rapidly absorbed from the canine gastrointestinal tract following oral administration.
After oral administration of 13.1 mg/kg bodyweight, the maximal plasma concentration of 6.4 µg/ml (Mean Cmax) is reached within 50 minutes (Mean Tmax). The biological plasma half-life of clindamycin in the dog is approximately 5 hours. No accumulation of bioactivity has been observed in dogs after several oral administrations.
Metabolism and Excretion
Extensive research of the metabolism and excretion pattern of clindamycin shows that the parent molecule as well as bioactive and bio-inactive metabolites are excreted via the urine and faeces. Nearly all bioactivity in the serum following oral administration is due to the parent molecule (clindamycin).