Capsule: Pharmacotherapeutic group:
Antibacterials for systemic use; macrolides, lincosamides and streptogramins, lincosamides. ATC code:
Clindamycin is a semi-synthetic pyranoside. Pyranosides do not show a relationship with other known antibiotics.
Mechanism of action:
The mechanism of action of clindamycin is based on the inhibition of protein biosynthesis due to binding to the 50s subunit of bacterial ribosome, resulting in a bacteriostatic effect for the most part.
Relationship between pharmacokinetics and pharmacodynamics:
The efficacy mainly depends on the duration of time during which agent level is above the minimum inhibitory concentration (MIC) of the pathogen.
Mechanism of resistance:
A resistance to clindamycin may be based on the following mechanisms: The resistance in staphylococci and streptococci is mostly based on an increased corporation of methyl groups into 23S rRNA (so-called constitutive MLSB resistance) with the binding affinity of clindamycin to the ribosome considerably reduced thereby.
The majority of methicillin-resistant S. aureus
(MRSA) shows the constitutive MLSB phenotype and is therefore clindamycin resistant. Infections due to macrolide-resistant staphylococci should not be treated with clindamycin even in case of proven in vitro sensitivity, as there is the risk that mutants with constitutive MLSB resistance are selected during therapy.
In strains with constitutive MLSB resistance, there is complete cross resistance of clindamycin with lincomycin, macrolides (e.g. azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin) as well as streptogramin B.
Clindamycin was tested while using the usual dilution series. The following minimal inhibitory concentrations were determined for susceptible and resistant germs: See Table 1.
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The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary; expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. Particularly in severe infections or if therapy has failed, microbiology diagnosis is to be attempted with the proof of the pathogen and its sensitivity to clindamycin. (See Table 2.)
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Clindamycin hydrochloride is absorbed quickly when administered orally.
The peak concentration in serum is achieved in. 45 to 60 minutes if taken on empty stomach and after two hours if taken at mealtimes, because absorption is delayed slightly by simultaneous intake of food.
The concentration remains above minimum inhibiting concentration (MIC) for most gram-positive organism for at least six hours when normal recommended doses are used.
The biological half-life of the produce is 2.4 hours.
The serum half-life is extended in patients with impaired renal function and moderate to severe hepatic insufficiency.
After absorption clindamycin is distributed quickly in body fluids, tissues including bone, but it does not reach the CSF in significant concentrations, even if the meninges are inflamed. It diffuses across the placenta into the foetal circulation and has been reported to appear in breast milk. High concentrations occur in bile. It accumulates in leucocytes and macrophages.
The binding of clindamycin to plasma proteins is concentration-dependent and lies in the therapeutic range between 60% and 94%.
The average volume of distribution is 1.1 L/kg.
Most of a clindamycin dose undergoes metabolism, and less than 10% of the dose is excreted unchanged in the urine. The known metabolites of clindamycin are N-demethyl clindamycin, clindamycin sulphoxide and N-demethyl clindamycin sulphoxide, which are excreted mainly in the faeces. Some metabolites have an anti-microbial activity. Agents which act as enzyme inducers in the liver reduce the mean dwell time of clindamycin in the body.
Clindamycin is eliminated for 2/3 in the faeces and 1/3 in the urine.
Toxicology: Preclinical safety data:
Symptoms of intoxication are decreased activity of the animals and convulsions.
After repeated doses (i.m.) of clindamycin to dogs an increase of the SGOT and SGPT was reported. And also a slight increase of the liver-weight without morphologic changes was documented. Long term administration of clindamycin to dogs induced damages to gastric mucosa and to the gallbladder.
Mutagenecity and cancerogenecity:
In vitro and in vivo studies did not reveal and mutagenic potential of clindamycin. Long-term studies in animals with regard to tumorigenic potential of clindamycin have not been carried out.
Studies with clindamycin in rats and mice did neither give a hint on fertility disorders nor embryofoetotoxic properties.
Solution for Injection:
Clindamycin is active against most gram-positive and gram-negative bacteria eg, Bacteroides
spp. Especially, it is highly active against Staphylococcus aureus
Clindamycin is better absorbed into gastrointestinal tract and has stronger antibacterial action. It has less side effect than lincomycin and shows better therapeutical profile.
Clindamycin injection is active against penicillin-resistant microorganism, hence it has been effectively used as replacement of penicillin preparations if applicable.