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=== Mechanism of action ===
=== Mechanism of action ===
Clindamycin has a [[bacteriostatic]] effect. It interferes with bacterial [[Protein biosynthesis|protein synthesis]] (in a similar way to [[erythromycin]], [[azithromycin]] and [[chloramphenicol]]), by binding preferentially to the [[50S]] subunit of the bacterial [[ribosome]].<ref name=Merck>{{cite web | url = http://www.merck.com/mmpe/print/sec14/ch170/ch170g.html | title = Lincosamides, Oxazolidinones, and Streptogramins | month = November | year = 2005 | accessdate = 2007-12-01 | publisher = [[Merck & Co.]], Inc. | work = [[Merck Manual of Diagnosis and Therapy]]}}</ref>
Clindamycin has a [[bacteriostatic]] effect. It interferes with bacterial [[Protein biosynthesis|protein synthesis]] by inhibiting [[robosomal translocation]],<ref>[http://sitemaker.umich.edu/mc3/clindamycin Wisteria Lane cases --> CLINDAMYCIN] University of Michigan. Retrieved on July 31, 2009</ref>, in a similar way to [[emacrolide]]s. It does so by binding preferentially to the [[50S]] subunit of the bacterial [[ribosome]].<ref name=Merck>{{cite web | url = http://www.merck.com/mmpe/print/sec14/ch170/ch170g.html | title = Lincosamides, Oxazolidinones, and Streptogramins | month = November | year = 2005 | accessdate = 2007-12-01 | publisher = [[Merck & Co.]], Inc. | work = [[Merck Manual of Diagnosis and Therapy]]}}</ref>


The structures of the complexes between several antibiotics (including clindamycin) and a ''[[Deinococcus radiodurans]]'' ribosome have been solved by [[X-ray crystallography]] by a team from the [[Max Planck Society|Max Planck Working Groups for Structural Molecular Biology]], and published in the journal ''[[Nature (journal)|Nature]]''.<ref>{{cite journal |author=Schlünzen F, Zarivach R, Harms J, ''et al.'' |title=Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria |journal=Nature |volume=413 |issue=6858 |pages=814–21 |year=2001 |pmid=11677599 |doi=10.1038/35101544}}</ref>
The structures of the complexes between several antibiotics (including clindamycin) and a ''[[Deinococcus radiodurans]]'' ribosome have been solved by [[X-ray crystallography]] by a team from the [[Max Planck Society|Max Planck Working Groups for Structural Molecular Biology]], and published in the journal ''[[Nature (journal)|Nature]]''.<ref>{{cite journal |author=Schlünzen F, Zarivach R, Harms J, ''et al.'' |title=Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria |journal=Nature |volume=413 |issue=6858 |pages=814–21 |year=2001 |pmid=11677599 |doi=10.1038/35101544}}</ref>

Revision as of 14:57, 31 July 2009

Clindamycin
Clinical data
Other names7-chloro-lincomycin
7-chloro-7-deoxylincomycin
Pregnancy
category
  • AU: A
Routes of
administration		Oral, topical, IV, intravaginal
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: WARNING[1]Rx-only
Pharmacokinetic data
Bioavailability90% (oral)
4–5% (topical)
Protein binding90%
MetabolismHepatic
Elimination half-life2–3 hours
ExcretionBiliary and renal (around 20%)
Identifiers
  • (2S,4R)-N-{2-chloro-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl}-1-methyl-4-propylpyrrolidine-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.038.357 Edit this at Wikidata
Chemical and physical data
FormulaC18H33ClN2O5S
Molar mass424.98 g/mol g·mol−1

Clindamycin (rINN; Template:PronEng) is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria. It is a common topical treatment for acne, and can be useful against some methicillin-resistant Staphylococcus aureus (MRSA) infections.[2]

The most severe common adverse effect of clindamycin is Clostridium difficile-associated diarrhea (the most frequent cause of pseudomembranous colitis). Although this side-effect occurs with almost all antibiotics, including beta-lactam antibiotics, it is classically linked to clindamycin use.[3]

Clindamycin is marketed under various trade names, including CLINCIN,Dalacin, Clindacin, Cleocin, and Evoclin (clindamycin by itself), Duac, BenzaClin, and Clindoxyl and Acanya (in combination with benzoyl peroxide), and Ziana (with tretinoin). Clindamycin is also available as a generic drug.

Indications

Clindamycin is used primarily to treat infections caused by susceptible anaerobic bacteria, including infections of the respiratory tract, skin and soft tissue infections, and peritonitis.[4] In patients with hypersensitivity to penicillins, clindamycin may be used to treat infections caused by susceptible aerobic bacteria as well. It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus.[4][5] Topical application of clindamycin phosphate can be used to treat mild to moderate acne.[6]

Bacterial

Combination therapy in acne

Multiple studies have shown the use of clindamycin in conjunction with benzoyl peroxide, which is available both through prescription or over-the-counter, to be more effective in the treatment of acne than the use of either product by itself.[7][8][9] A single-blind study comparing this combination to adapalene, a retinoid, also found it to work faster and be significantly better tolerated than adapalene, as well as more effective.[10]

Clindamycin and adapalene in combination are also more effective than either drug alone, although adverse effects are more frequent;[11] a single study found pretreatment with adapalene (application of adapalene 3–5 minutes before clindamycin) to significantly increase the penetration of clindamycin into the skin, which may enhance efficacy.[12]

Susceptible bacteria

It is most effective against infections involving the following types of organisms:

Most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus influenzae and Moraxella) are resistant to clindamycin,[13][14] as are the facultative anaerobic Enterobacteriaceae.[15] A notable exception is Capnocytophaga canimorsus, for which clindamycin is a first-line drug of choice.[16]

Other

It can also be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA);[2] many strains of MRSA are still susceptible to clindamycin.

Clindamycin is used in cases of suspected toxic shock syndrome,[17] often in combination with a bactericidal agent such as vancomycin. The rationale for this approach is a presumed synergy between vancomycin, which causes the death of the bacteria by breakdown of the cell membrane, and clindamycin, which is a powerful inhibitor of toxin synthesis. Both in vitro and in vivo studies have shown that clindamycin reduces the production of exotoxins by staphylococci;[18] it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis).[19][20]

Clindamycin has been proven to decrease the risk of premature births in women diagnosed with bacterial vaginosis during early pregnancy to about a third of the risk of untreated women.[21]

Parasitic

Malaria

Given with chloroquine or quinine, clindamycin is effective and well-tolerated in treating Plasmodium falciparum malaria; the latter combination is particularly useful for children, and is the treatment of choice for pregnant women who become infected in areas where resistance to chloroquine is common.[22][23] Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.[22][23]

Other

The combination of clindamycin and quinine is the standard treatment for severe babesiosis.[24]

Clindamycin may also be used to treat toxoplasmosis,[13][25][26] and, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.[27]

Available forms

Clindamycin preparations for oral administration include capsules (containing clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate hydrochloride). Oral suspension is not favored for administration of clindamycin to children, due to its extremely foul taste. It is also available for topical administration, in gel form and in a foam delivery system (both containing clindamycin phosphate) and a solution in ethanol (containing clindamyin hydrochloride) and is used primarily as a prescription acne treatment.

Several combination acne treatments containing clindamycin are also marketed, such as single-product formulations of clindamycin with benzoyl peroxide—sold as BenzoClin (Sanofi-Aventis), Duac (a gel form made by Stiefel), and Acanya, among other trade names—and, in the United States, a combination of clindamycin and tretinoin, sold as Ziana.[28] In India, vaginal suppositories containing clindamycin in combination with clotrimazole are manufactured by Olive Health Care and sold as Clinsup-V. In Egypt, vaginal cream containing clindamycin produced by Biopharmgroup sold as "Vagiclind" indicated for vaginosis.

Clindamycin is available as a generic drug, for both systemic (oral and intravenous) and topical use.

Adverse effects

Common adverse drug reactions (ADRs) associated with clindamycin therapy—found in over 1% of patients—include: diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain or cramps, rash, and/or itch. High doses (both intravenous and oral) may cause a metallic taste, and topical application may cause contact dermatitis.[29]

Pseudomembranous colitis is a potentially-lethal condition commonly associated with clindamycin, but which also occurs with other antibiotics.[3][30] Overgrowth of Clostridium difficile, which is inherently resistant to clindamycin, results in the production of a toxin that causes a range of adverse effects, from diarrhea to colitis and toxic megacolon.[29]

Rarely—in less than 0.1% of patients—clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzyme levels and/or hepatotoxicity.[29]

Chemistry

Clindamycin is a semisynthetic derivative of lincomycin, a natural antibiotic produced by the actinobacterium Streptomyces lincolnensis. It is obtained by 7(S)-chloro-substitution of the 7(R)-hydroxyl group of lincomycin.[31]

Pharmacology

Pharmacokinetics

Approximately 90% of an oral dose of clindamycin is absorbed from the gastrointestinal tract and it is widely distributed throughout the body, excluding the central nervous system. Adequate therapeutic concentrations can be achieved in bone. There is also active uptake into white blood cells, most importantly neutrophils.[32]

Clindamycin is extensively metabolised in the liver, probably by CYP3A4;[33][34] some of its metabolites are active, such as N-dimethyl clindamycin and clindamycin sulfoxide. The elimination half-life is 1.5 to 5 hours. Clindamycin is primarily eliminated by hepatic metabolism; after an intravenous dose of clindamycin phosphate, about 4.5% of the dose is excreted in urine as clindamycin and about 0.35% as the phosphate salt.[35] The metabolites are excreted primarily in the urine.[36]

Mechanism of action

Clindamycin has a bacteriostatic effect. It interferes with bacterial protein synthesis by inhibiting robosomal translocation,[37], in a similar way to emacrolides. It does so by binding preferentially to the 50S subunit of the bacterial ribosome.[13]

The structures of the complexes between several antibiotics (including clindamycin) and a Deinococcus radiodurans ribosome have been solved by X-ray crystallography by a team from the Max Planck Working Groups for Structural Molecular Biology, and published in the journal Nature.[38]

Interactions

Clindamycin may prolong the effects of neuromuscular-blocking drugs.[39][40][41][42] Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism[14] and possible cross-resistance.

Veterinary use

The veterinary uses of clindamycin are quite similar to its human indications, and include treatment of osteomyelitis,[43] skin infections, and toxoplasmosis, for which it is the drug of choice in dogs and cats.[44] Toxoplasmosis rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats. Toxoplasmosis is contagious to humans, and therefore cat owners, particularly pregnant women, should take precautions to prevent the spread of the disease.

See also

References

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  2. ^ a b Daum RS (2007). "Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus". N Engl J Med. 357 (4): 380–90. doi:10.1056/NEJMcp070747. PMID 17652653.
  3. ^ a b Thomas C, Stevenson M, Riley TV (2003). "Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review". J Antimicrob Chemother. 51 (6): 1339–50. doi:10.1093/jac/dkg254. PMID 12746372.{{cite journal}}: CS1 maint: multiple names: authors list (link) Free full text
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External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Clindamycin&oldid=305272016"