Clindagen Mechanism of Action

Pharmacology: Clindamycin is a lincosamide bacteriostatic antibiotic that exerts action against Gram-positive organisms and a wide scope of anaerobic pathogens. It inhibits the early stages of protein synthesis by interfering with the formation of initiation complexes and with aminoacyl translocation reactions.
Pharmacokinetics: Following oral administration, the bioavailability of the drug is about 90% with 150 mg dose and 23-38% with higher doses.
An hour after a single dose of 150 mg oral clindamycin plasma concentration reaches 2-3 mcg/mL. After 6 hours, it increases to an average of 0.7 mg/mL. Peak plasma concentrations are 4 mcg/mL for 300 mg dose and 8 mcg/mL for 600 mg dose.
Food reduces the rate of absorption of clindamycin but does not affect the extent of absorption of the drug.
Clindamycin is about 90% protein bound. Its half life is 2-3 hours and is prolonged to 3.5 to 5 hours in patients with anuria, and to 7-14 hours in patients with liver disease. Half life is also prolonged in preterm neonates.
Clindamycin is metabolized in the liver to its active metabolites. N-demethyl and sulfoxide metabolites and to some inactive ones.
The volume of distribution of clindamycin is 0.66 mL/g. It is distributed in most tissues, body fluids and bone. Significant concentration of clindamycin enough to treat meningitis is not reached in the cerebrospinal fluid.
Clindamycin is eliminated in the liver and is slowly excreted as active drug and metabolites in the urine (10%) and in the feces (4%). Clindamycin cannot be removed by dialysis.
In patients with AIDS, clindamycin shows higher bioavailability. Plasma clearance and volume of distribution is lower.
Microbiology: Spectrum: Clindamycin exerts bacteriostatic action against Gram-positive organisms such as streptococci, staphylococci, Bacillus anthracis, and Corynebacterium diphtheriae.
Among the Gram-positive anaerobes susceptible to clindamycin are Eubacterium, Propionibacterium, Peptococcus, Peptostreptococcus, C. perfringens, and C. tetani. Susceptible Gram-negative anaerobes include Fusobacterium spp. (except F. varium). Prevotella spp., and Bacteroides spp. including the group of B. fragilis.
Also reported to be susceptible to clindamycin are several Actinomyces spp., and Nocardia asteroides.
Clindamycin has been reported to be active against some protozoa such as Toxoplasma gondii and Plasmodium.
In high concentrations, clindamycin may become bactericidal against sensitive strains.
Antimicrobial Resistance: Mycoplasma spp., enterococci, and most Gram negative aerobes such as Enterobacteriaceae are resistant to clindamycin.
Other organisms which may also be resistant to clindamycin are methicillin-resistant strains of Staphylococcus aureus, Neisseria gonorrhea, N. meningitides and Haemophilus influenzae. Reports of decreased resistance among B. fragilis group have been received.
Clindamycin is not effective against fungi, yeasts and viruses, although it has some protozoal activity. (See previously mentioned under Spectrum and Indications.)
Cross resistance due to the methylation of the ribosome exists between lincosamides and macrolides. The receptor on the 50S subunit of the bacterial ribosome, 23S rRNA, is perhaps identical with the receptor for macrolides. Thus, these drugs may interfere with each other.
Complete cross resistance occurs when clindamycin is given with lincomycin.
Effect when given with other antimicrobials: When given with ceftazidime, metronidazole or ciprofloxacin, clindamycin shows a synergistic effect against some anaerobes. Clindamycin may also competitively inhibit the effect of macrolides or chloramphenicol because their receptors on bacterial ribosomes are adjacent.
In vitro, clindamycin diminishes activity of ampicillin against Staphylococcus aureus and is said to enhance the activity of primaquine against Pneumocystis jirovecii.