Clindamycin

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Clindamycin
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200px
Systematic (IUPAC) name
(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
Clinical data
Pregnancy
category
  • AU: A
  • US: B (No risk in non-human studies)
Routes of
administration		 Oral, topical, IV, intravaginal
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability 90% (oral)
4–5% (topical)
Protein binding 95%
Metabolism Hepatic
Biological half-life 2–3 hours
Excretion Biliary and renal (around 20%)
Identifiers
CAS Number 18323-44-9
ATC code J01FF01 (WHO) D10AF01 G01AA10
PubChem CID 446598
DrugBank APRD00566
ChemSpider 393915
Synonyms 7-chloro-lincomycin
7-chloro-7-deoxylincomycin
Chemical data
Formula C18H33ClN2O5S
Molar mass 424.98 g/mol[[Script error: No such module "String".]]
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Clindamycin (rINN; pronounced /klɪndəˈmaɪsɨn/) 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.[1]

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.[2]

Clindamycin is marketed under various trade names, including Dalacin, 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.[3] 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.[3][4] Topical application of clindamycin phosphate can be used to treat mild to moderate acne.[5]

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.[6][7][8] 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.[9]

Clindamycin and adapalene in combination are also more effective than either drug alone, although adverse effects are more frequent;[10] 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.[11]

Susceptible bacteria (spectrum of activity)

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,[12][13] as are the facultative anaerobic Enterobacteriaceae.[14] A notable exception is Capnocytophaga canimorsus, for which clindamycin is a first-line drug of choice.[15]

Other

It can also be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA);[1] many strains of MRSA are still susceptible to clindamycin.

Clindamycin is used in cases of suspected toxic shock syndrome,[16] 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;[17] it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis).[18][19]

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.[20]

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.[21][22] Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.[21][22]

Other

The combination of clindamycin and quinine is the standard treatment for severe babesiosis.[23]

Clindamycin may also be used to treat toxoplasmosis,[12][24][25] and, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.[26]

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 and odor. Clindamycin is also formulated in a vaginal cream and as vaginal suppositories for treatment of bacterial vaginosis. 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 BenzaClin (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.[27] 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. (The exceptions are the oral suspension and vaginal suppositories, which are not available as generics in the USA.)

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.[28] Diarrhea, vomiting, and nausea are common if the individual lies down for an extended period of time within 30 minutes of taking Clindamycin. In addition, severe heart burn can be expected for up to 3 days if the individual does not stay in an elevated position for at least 30 minutes.

Pseudomembranous colitis is a potentially-lethal condition commonly associated with clindamycin, but which occurs with other antibiotics as well.[2][29] 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.[28]

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.[28]

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.[30]

Pharmacology

Mechanism of action

Clindamycin has a bacteriostatic effect. It is a bacterial protein synthesis inhibitor by inhibiting ribosomal translocation,[31] in a similar way to macrolides. It does so by binding preferentially to the 23S rRNA of the large bacterial ribosome subunit.[12]

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.[32]

Interactions

Clindamycin may prolong the effects of neuromuscular-blocking drugs.[33][34][35][36] Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism[13] and possible cross-resistance.

Veterinary use

The veterinary uses of clindamycin are quite similar to its human indications, and include treatment of osteomyelitis,[37] skin infections, and toxoplasmosis, for which it is the preferred drug in dogs and cats.[38] 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; in particular, pregnant women should take precautions to prevent the spread of the disease.

See also

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References

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External links

Acne-treating agents (D10)
Antibacterial
Keratolytic
Anti-inflammatory
Antibiotics
Hormonal
Retinoids
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Antibiotics
Arsenic compounds
Quinoline derivatives
Organic acids
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30S
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Tetracyclines
50S
Clindamycin#  · Lincomycin
EF-G
Steroid antibacterials

M: BAC

drug(J1p, w, n, m, vacc)

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Individual
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Atovaquone (always combined with proguanil as Malarone)
Tetracycline • Doxycycline#
Clindamycin
Combi-
nations
Fixed-dose (coformulated) ACTs
Coartem# • ASAQ (Coarsucam) • ASMQ •
Duo-Cotecxin (Artekin) • Pyramax
Combination therapies
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Quinine/tetracycline • Quinine/clindamycin •
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Clindamycin
Hetero-
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bn:ক্লিন্ডামাইসিন

de:Clindamycin dv:ކްލިންޑަމައިސިން es:Clindamicina fa:کلیندامایسین fr:Clindamycine it:Clindamicina hu:Klindamicin nl:Clindamycine ja:クリンダマイシン pl:Klindamycyna pt:Clindamicina ru:Клиндамицин fi:Klindamysiini sv:Klindamycin

th:คลินดามัยซิน
  1. ↑ 1.0 1.1 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. 
  2. ↑ 2.0 2.1 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.  Free full text
  3. ↑ 3.0 3.1 "Cleocin I.V. Indications & Dosage". RxList.com. 2007. Retrieved 2007-12-01. 
  4. ↑ Darley ES, MacGowan AP (2004). "Antibiotic treatment of gram-positive bone and joint infections". J Antimicrob Chemother. 53 (6): 928–35. doi:10.1093/jac/dkh191. PMID 15117932.  Free full text
  5. ↑ Feldman S, Careccia RE, Barham KL, Hancox J (2004). "Diagnosis and treatment of acne". Am Fam Physician. 69 (9): 2123–30. PMID 15152959.  Free full text
  6. ↑ Cunliffe WJ, Holland KT, Bojar R, Levy SF (2002). "A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide gel formulation and a matching clindamycin gel with respect to microbiologic activity and clinical efficacy in the topical treatment of acne vulgaris". Clin Ther. 24 (7): 1117–33. doi:10.1016/S0149-2918(02)80023-6. PMID 12182256. 
  7. ↑ Leyden JJ, Berger RS, Dunlap FE, Ellis CN, Connolly MA, Levy SF (2001). "Comparison of the efficacy and safety of a combination topical gel formulation of benzoyl peroxide and clindamycin with benzoyl peroxide, clindamycin and vehicle gel in the treatments of acne vulgaris". Am J Clin Dermatol. 2 (1): 33–9. doi:10.2165/00128071-200102010-00006. PMID 11702619. 
  8. ↑ Lookingbill DP, Chalker DK, Lindholm JS; et al. (1997). "Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations". J Am Acad Dermatol. 37 (4): 590–5. doi:10.1016/S0190-9622(97)70177-4. PMID 9344199. 
  9. ↑ Langner A, Chu A, Goulden V, Ambroziak M (2008). "A randomized, single-blind comparison of topical clindamycin + benzoyl peroxide and adapalene in the treatment of mild to moderate facial acne vulgaris". Br J Dermatol. 158 (1): 122–9. doi:10.1111/j.1365-2133.2007.08308.x. PMID 18047518. 
  10. ↑ Wolf JE, Kaplan D, Kraus SJ; et al. (2003). "Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study". J Am Acad Dermatol. 49 (3 Suppl): S211–7. doi:10.1067/S0190-9622(03)01152-6. PMID 12963897. 
  11. ↑ Jain GK, Ahmed FJ (2007). "Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies". Indian J Dermatol Venereol Leprol. 73 (5): 326–9. doi:10.4103/0378-6323.34010. PMID 17921613.  Free full text
  12. ↑ 12.0 12.1 12.2 12.3 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  13. ↑ 13.0 13.1 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  14. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. Retrieved on January 19, 2009 through Google Book Search.
  15. ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  16. ↑ Annane D, Clair B, Salomon J (2004). "Managing toxic shock syndrome with antibiotics". Expert Opin Pharmacother. 5 (8): 1701–10. doi:10.1517/14656566.5.8.1701. PMID 15264985. 
  17. ↑ Coyle EA, Society of Infectious Diseases Pharmacists (2003). "Targeting bacterial virulence: the role of protein synthesis inhibitors in severe infections. Insights from the Society of Infectious Diseases Pharmacists". Pharmacotherapy. 23 (5): 638–42. doi:10.1592/phco.23.5.638.32191. PMID 12741438.  Free full text with registration at Medscape
  18. ↑ Gemmell CG, O'Dowd A (1983). "Regulation of protein A biosynthesis in Staphylococcus aureus by certain antibiotics: its effect on phagocytosis by leukocytes". J Antimicrob Chemother. 12 (6): 587–97. doi:10.1093/jac/12.6.587. PMID 6662837. 
  19. ↑ Gemmell CG, Peterson PK, Schmeling D; et al. (1981). "Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin". J Clin Invest. 67 (5): 1249–56. doi:10.1172/JCI110152. PMC 370690 Freely accessible. PMID 7014632.  Full text at PMC: 370690.
  20. ↑ Lamont RF (2005). "Can antibiotics prevent preterm birth—the pro and con debate". BJOG. 112 Suppl 1: 67–73. doi:10.1111/j.1471-0528.2005.00589.x. PMID 15715599. 
  21. ↑ 21.0 21.1 Lell B, Kremsner PG (2002). "Clindamycin as an antimalarial drug: review of clinical trials". Antimicrob Agents Chemother. 46 (8): 2315–20. doi:10.1128/AAC.46.8.2315-2320.2002. PMC 127356 Freely accessible. PMID 12121898.  Free full text
  22. ↑ 22.0 22.1 Griffith KS, Lewis LS, Mali S, Parise ME (2007). "Treatment of malaria in the United States: a systematic review". JAMA. 297 (20): 2264–77. doi:10.1001/jama.297.20.2264. PMID 17519416.  Free full text
  23. ↑ Homer MJ, Aguilar-Delfin I, Telford SR, Krause PJ, Persing DH (2000). "Babesiosis". Clin Microbiol Rev. 13 (3): 451–69. doi:10.1128/CMR.13.3.451-469.2000. PMC 88943 Freely accessible. PMID 10885987.  Free full text
  24. ↑ Pleyer U, Torun N, Liesenfeld O (2007). "[Ocular toxoplasmosis]". Ophthalmologe (in German). 104 (7): 603–15, quiz 616. doi:10.1007/s00347-007-1535-8. PMID 17530262. 
  25. ↑ Jeddi A, Azaiez A, Bouguila H; et al. (1997). "[Value of clindamycin in the treatment of ocular toxoplasmosis]". J Fr Ophtalmol (in French). 20 (6): 418–22. PMID 9296037. 
  26. ↑ Fishman JA (1998). "Treatment of infection due to Pneumocystis carinii". Antimicrob Agents Chemother. 42 (6): 1309–14. PMC 105593 Freely accessible. PMID 9624465.  Free full text
  27. ↑ Waknine, Yael (December 1, 2006). "FDA Approvals: Ziana, Kadian, Polyphenon E" (free registration required). Medscape. Retrieved 2007-12-01. 
  28. ↑ 28.0 28.1 28.2 Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
  29. ↑ Starr J (2005). "Clostridium difficile associated diarrhoea: diagnosis and treatment". BMJ. 331 (7515): 498–501. doi:10.1136/bmj.331.7515.498. PMC 1199032 Freely accessible. PMID 16141157.  Free full text
  30. ↑ Meyers BR, Kaplan K, Weinstein L (1969). "Microbiological and pharmacological behavior of 7-chlorolincomycin". Appl Microbiol. 17 (5): 653–7. PMC 377774 Freely accessible. PMID 4389137.  Full text at PMC: 377774
  31. ↑ Wisteria Lane cases --> CLINDAMYCIN University of Michigan. Retrieved on July 31, 2009
  32. ↑ Schlünzen F, Zarivach R, Harms J; et al. (2001). "Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria". Nature. 413 (6858): 814–21. doi:10.1038/35101544. PMID 11677599. 
  33. ↑ "Cleocin I.V. Side Effects & Drug Interactions". RxList.com. 2007. Retrieved 2007-12-01. 
  34. ↑ Fogdall RP, Miller RD (1974). "Prolongation of a pancuronium-induced neuromuscular blockade by clindamycin". Anesthesiology. 41 (4): 407–8. doi:10.1097/00000542-197410000-00023. PMID 4415332. 
  35. ↑ al Ahdal O, Bevan DR (1995). "Clindamycin-induced neuromuscular blockade". Can J Anaesth. 42 (7): 614–7. doi:10.1007/BF03011880. PMID 7553999. 
  36. ↑ Sloan PA, Rasul M (2002). "Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium". Anesth Analg. 94 (1): 123–4, table of contents. doi:10.1097/00000539-200201000-00023. PMID 11772813.  Free full text
  37. ↑ (February 8, 2005) "Osteomyelitis", in Kahn, Cynthia M., Line, Scott, Aiello, Susan E. (ed.): The Merck Veterinary Manual, 9th ed., John Wiley & Sons. ISBN 0-911910-50-6. Retrieved on 14 December 2007.
  38. ↑ (February 8, 2005) "Toxoplasmosis: Introduction", in Kahn, Cynthia M., Line, Scott, Aiello, Susan E. (ed.): The Merck Veterinary Manual, 9th ed., John Wiley & Sons. ISBN 0-911910-50-6. Retrieved on 14 December 2007.
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