Clindamycin

Clindamycin

Systematic (IUPAC) name
methyl 7-chloro-6,7,8-trideoxy-6-{[(4R)-1-methyl-4-propyl-L-prolyl]amino}-1-thio-L-threo-α-D-galacto-octopyranoside
Clinical data
Trade names	Cleocin, Daclin
AHFS/Drugs.com	monograph
MedlinePlus	a682399
Licence data	US FDA:link
Pregnancy cat.	A(AU) B(US)
Legal status	Prescription Only (S4) (AU) POM (UK) ℞-only (US)
Routes	Oral, topical, IV, intravaginal
Pharmacokinetic data
Bioavailability	90% (oral) 4–5% (topical)
Protein binding	95%
Metabolism	Hepatic
Half-life	2–3 hours
Excretion	Biliary and renal (around 20%)
Identifiers
CAS number	18323-44-9 Y
ATC code	J01FF01 D10AF01 G01AA10
PubChem	CID 446598
DrugBank	APRD00566
ChemSpider	393915 Y
UNII	3U02EL437C Y
KEGG	D00277 Y
ChEMBL	CHEMBL187 N
Synonyms	7-chloro-lincomycin 7-chloro-7-deoxylincomycin
Chemical data
Formula	C18H33ClN2O5S
Mol. mass	424.98 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C18H33ClN2O5S/c1-5-6-10-7-11(21(3)8-10)17(25)20-12(9(2)19)16-14(23)13(22)15(24)18(26-16)27-4/h9-16,18,22-24H,5-8H2,1-4H3,(H,20,25)/t9-,10+,11-,12+,13-,14+,15+,16+,18+/m0/s1 Y Key:KDLRVYVGXIQJDK-AWPVFWJPSA-N Y
N(what is this?)  (verify)

Clindamycin rINN ( /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, ''Daclin''. Combination products include Duac, BenzaClin, 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 anaerobic infections caused by susceptible anaerobic bacteria, including dental infections,^[3] and 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 (spectrum of activity)

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

• Aerobic Gram-positive cocci, including some members of the Staphylococcus and Streptococcus (e.g. pneumococcus) genera, but not enterococci.^[13]
• Anaerobic, Gram-negative rod-shaped bacteria, including some Bacteroides, Fusobacterium, and Prevotella, although resistance is increasing in Bacteroides fragilis.

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);^[1] many strains of MRSA are still susceptible to clindamycin; however, in the United States spreading from the West Coast eastwards, MRSA is becoming increasingly resistant.

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] Patient-derived isolates of Plasmodium falciparum from the Peruvian Amazon have been reported to be resistant to clindamycin as evidenced by in vitro drug susceptibility testing.^[24]

Other

The combination of clindamycin and quinine is the standard treatment for severe babesiosis.^[25]

Clindamycin may also be used to treat toxoplasmosis,^[13][26][27] and, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.^[28]

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 clindamycin 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.^[29] 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.^{[citation needed]} (The exceptions are the oral suspension and vaginal suppositories, which are not available as generics in the USA.)^{[citation needed]}

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.^[30] 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 heartburn can be expected for up to three 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][31] 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.^[30]

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.^[30]

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.^[32]

Mechanism of action

Clindamycin has a bacteriostatic effect. It is a bacterial protein synthesis inhibitor by inhibiting ribosomal translocation,^[33] in a similar way to macrolides. It does so by binding to the 50S rRNA of the large bacterial ribosome subunit.^[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.^[34]

Interactions

Clindamycin may prolong the effects of neuromuscular-blocking drugs.^{[35][36][37][38]} 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,^[39] skin infections, and toxoplasmosis, for which it is the preferred drug in dogs and cats.^[40] Toxoplasmosis rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats. Toxoplasmosis is zoonotic (communicable from animals to humans), so cat owners, pregnant women in particular, should take precautions to prevent the spread of the disease

See also

Pharmacy and Pharmacology portal

• Protein synthesis inhibitor

References

1. ^ ^{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. 
2. ^ ^{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. http://jac.oxfordjournals.org/content/51/6/1339.full.pdf. 
3. ^ Brook I, Lewis MA, Sándor GK, Jeffcoat M, Samaranayake LP, Vera Rojas J. Clindamycin in dentistry: more than just effective prophylaxis for endocarditis? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 ;100:550-8
4. ^ ^{a b} "Cleocin I.V. Indications & Dosage". RxList.com. 2007. http://www.rxlist.com/cgi/generic/clindamyciniv_ids.htm. Retrieved 2007-12-01. 
5. ^ 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. http://jac.oxfordjournals.org/content/53/6/928.full.pdf. 
6. ^ Feldman S, Careccia RE, Barham KL, Hancox J (May 2004). "Diagnosis and treatment of acne". Am Fam Physician 69 (9): 2123–30. PMID 15152959. http://www.aafp.org/afp/2004/0501/p2123.pdf. 
7. ^ 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. 
8. ^ 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. 
9. ^ 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. 
10. ^ 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. 
11. ^ 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. 
12. ^ 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. 
13. ^ ^{a b c d} "Lincosamides, Oxazolidinones, and Streptogramins". Merck Manual of Diagnosis and Therapy. Merck & Co.. November 2005. http://www.merck.com/mmpe/print/sec14/ch170/ch170g.html. Retrieved 2007-12-01. 
14. ^ ^{a b} Bell EA (January 2005). "Clindamycin: new look at an old drug". Infectious Diseases in Children. http://www.pediatricsupersite.com/view.aspx?rid=35957. Retrieved 2007-12-01. ^{[dead link]}
15. ^ Gold, Howard S.; Robert C. Moellering, Jr. (1999). "Macrolides and clindamycin". In Root, Richard E.; Francis Waldvogel, Lawrence Corey, Walter E. Stamm. Clinical infectious diseases: a practical approach. Oxford: Oxford University Press. pp. 291–7. ISBN 0-19-508103-X. http://books.google.com/books?id=zvCOpighJggC&pg=PA294.  Retrieved January 19, 2009 through Google Book Search.
16. ^ Jolivet-Gougeon A, Sixou JL, Tamanai-Shacoori Z, Bonnaure-Mallet M (April 2007). "Antimicrobial treatment of Capnocytophaga infections". Int J Antimicrob Agents 29 (4): 367–73. doi:10.1016/j.ijantimicag.2006.10.005. PMID 17250994. 
17. ^ 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. 
18. ^ 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. http://www.medscape.com/viewarticle/455753. 
19. ^ 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. 
20. ^ 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. PMID 7014632. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=370690. 
21. ^ 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. 
22. ^ ^{a b} Lell B, Kremsner PG (2002). "Clindamycin as an Antimalarial Drug: Review of Clinical Trials". Antimicrobial Agents and Chemotherapy 46 (8): 2315–20. doi:10.1128/AAC.46.8.2315-2320.2002. ISSN 0066-4804. PMC 127356. PMID 12121898. http://aac.asm.org/cgi/reprint/46/8/2315.pdf. 
23. ^ ^{a b} 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. http://jama.ama-assn.org/content/297/20/2264.full.pdf. 
24. ^ Dharia NV, Plouffe D, Bopp SE, González-Páez GE, Lucas C, Salas C, Soberon V, Bursulaya B, Kochel TJ, Bacon DJ, Winzeler EA (2010). "Genome scanning of Amazonian Plasmodium falciparum shows subtelomeric instability and clindamycin-resistant parasites". Genome Research 20 (11): 1534–44. doi:10.1101/gr.105163.110. PMC 2963817. PMID 20829224. http://genome.cshlp.org/content/20/11/1534.long. 
25. ^ Homer MJ, Aguilar-Delfin I, Telford SR, Krause PJ, Persing DH (July 2000). "Babesiosis". Clin Microbiol Rev 13 (3): 451–69. doi:10.1128/CMR.13.3.451-469.2000. PMC 88943. PMID 10885987. http://cmr.asm.org/cgi/reprint/13/3/451.pdf. 
26. ^ Pleyer U, Torun N, Liesenfeld O (2007). "Okuläre Toxoplasmose [Ocular toxoplasmosis]" (in German). Ophthalmologe 104 (7): 603–16. doi:10.1007/s00347-007-1535-8. PMID 17530262. 
27. ^ Jeddi A, Azaiez A, Bouguila H, et al. (1997). "Intérêt de la clindamycine dans le traitement de la toxoplasmose oculaire [Value of clindamycin in the treatment of ocular toxoplasmosis]" (in French). Journal français d'ophtalmologie 20 (6): 418–22. ISSN 0181-5512. PMID 9296037. 
28. ^ Fishman JA (June 1998). "Treatment of Infection Due to Pneumocystis carinii". Antimicrobial Agents and Chemotherapy 42 (6): 1309–14. ISSN 0066-4804. PMC 105593. PMID 9624465. http://aac.asm.org/cgi/reprint/42/6/1309.pdf. 
29. ^ Waknine, Yael (December 1, 2006). "FDA Approvals: Ziana, Kadian, Polyphenon E" (free registration required). Medscape Medical News. http://www.medscape.com/viewarticle/548709. Retrieved 2007-12-01. 
30. ^ ^{a b c} Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
31. ^ Starr J (2005). "Clostridium difficile associated diarrhoea: diagnosis and treatment". BMJ 331 (7515): 498–501. doi:10.1136/bmj.331.7515.498. PMC 1199032. PMID 16141157. http://www.bmj.com/cgi/content/full/331/7515/498. 
32. ^ Meyers BR, Kaplan K, Weinstein L (1969). "Microbiological and Pharmacological Behavior of 7-Chlorolincomycin". Appl Microbiol 17 (5): 653–7. PMC 377774. PMID 4389137. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=377774. 
33. ^ Clindamycin University of Michigan. Retrieved July 31, 2009
34. ^ 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. 
35. ^ "Cleocin I.V. Side Effects & Drug Interactions". RxList.com. 2007. http://www.rxlist.com/cgi/generic/clindamyciniv_ad.htm. Retrieved 2007-12-01. 
36. ^ 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. 
37. ^ al Ahdal O, Bevan DR (1995). "Clindamycin-induced neuromuscular blockade". Can J Anaesth 42 (7): 614–7. doi:10.1007/BF03011880. PMID 7553999. 
38. ^ 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. http://www.anesthesia-analgesia.org/content/94/1/123.full.pdf. 
39. ^ (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 14 December 2007.
40. ^ (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 14 December 2007.

External links

• Clindamycin drug information from Lexi-Comp. Includes dosage information and a comprehensive list of international brand names.