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Clindamycin

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Clindamycin
File:Clindamycin skeletal.svg
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-((1R)-2-chloro-
    1-((3R,4R,5S,6R)-3,4,5-trihydroxy-
    6-(methylthio)-tetrahydro-2H-pyran-2-yl)propyl)-
    1-methyl-4-propylpyrrolidine-2-carboxamide
CAS Number
PubChem CID
DrugBank
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 alone and in combination with other drugs under various trade names, including Dalacin and Cleocin (manufactured by Pfizer), and in a foam as Evoclin (Connetics) and Duac (with benzoyl peroxide, made by Stiefel). It 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, septicemia 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.[5][4] Topical application of clindamycin phosphate can be used to treat mild to moderate acne.[6]

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]

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.[13][14] Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.[13][14]

Other uses

Clindamycin is used occasionally in cases of suspected toxic shock syndrome,[15] in combination with a bactericidal agent such as vancomycin. The rationale for this approach is a presumed synergy between the bactericidal antibiotic, which causes the death of the bacteria by breakdown of the cell membrane, and clindamycin, which inhibits toxin synthesis.

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.[16]

Recently, clindamycin has been found to be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus.[2]

The combination of clindamycin and quinine is the standard treatment for severe babesiosis.[17] Clindamycin may also be used to treat toxoplasmosis.[18][19][20]

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), as well as the facultative anaerobic Enterobacteriaceae, are resistant to clindamycin.[18][21]

Available forms

Clindamycin preparations for oral administration include capsules (containing clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate hydrochloride). It is also available for topical administration, in gel form and in a foam delivery system (both containing clindamycin phosphate), primarily as a prescription acne treatment. The combination of clindamycin and benzoyl peroxide in a single product is also available, as is (in the United States) a combination of clindamycin and tretinoin, sold as Ziana.[22]

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 intravenous doses may cause a metallic taste, and topical application may cause contact dermatitis.[23]

Pseudomembranous colitis is a potentially-lethal condition commonly associated with clindamycin, but which also occurs with other antibiotics.[24][3] 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.[23]

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.[23]

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.[25]

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.[26]

Clindamycin is extensively metabolised in the liver, probably by CYP3A4;[27][28] 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.[29] The metabolites are excreted primarily in the urine.[30]

Mechanism of action

Clindamycin has a bacteriostatic effect. It interferes with bacterial protein synthesis, in a similar way to erythromycin, azithromycin and chloramphenicol, by binding to the 50S subunit of the bacterial ribosome.[18]

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.[31]

Interactions

Clindamycin may prolong the effects of neuromuscular-blocking drugs.[32][33][34][35] Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism[21] and possible cross-resistance.

Veterinary use

The veterinary uses of clindamycin are quite similar to its human indications, and include treatment of osteomyelitis,[36] skin infections, and toxoplasmosis, for which it is the drug of choice in dogs and cats.[37] 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.

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  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
  4. ^ a b "Cleocin I.V. Indications & Dosage". RxList.com. 2007. 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. Free full text
  6. ^ Feldman S, Careccia RE, Barham KL, Hancox J (2004). "Diagnosis and treatment of acne". Am Fam Physician. 69 (9): 2123–30. PMID 15152959.{{cite journal}}: CS1 maint: multiple names: authors list (link) Free full text
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  13. ^ a b Lell B, Kremsner PG (2002). "Clindamycin as an antimalarial drug: review of clinical trials". Antimicrob Agents Chemother. 46 (8): 2315–20. PMID 12121898. Free full text
  14. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link) Free full text
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  19. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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  23. ^ a b c Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
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  27. ^ Wynalda MA, Hutzler JM, Koets MD, Podoll T, Wienkers LC (2003). "In vitro metabolism of clindamycin in human liver and intestinal microsomes". Drug Metab Dispos. 31 (7): 878–87. doi:10.1124/dmd.31.7.878. PMID 12814964.{{cite journal}}: CS1 maint: multiple names: authors list (link) Free full text
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  36. ^ (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 2007-12-14.
  37. ^ (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 2007-12-14.
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