Clindamycin

Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infections), and endocarditis.<ref name=AHFS2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It can also be used to treat acne,<ref name=AHFS2015/><ref name=Ley2006/> and some cases of methicillin-resistant Staphylococcus aureus (MRSA).<ref name=Daum2007>Template:Cite journal</ref> In combination with quinine, it can be used to treat malaria.<ref name=AHFS2015/><ref name=Ley2006/> It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.<ref name="Xaciato FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=AHFS2015/><ref name=Ley2006>Template:Cite book</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite press release</ref>

Common side effects include nausea and vomiting, diarrhea, skin rashes, and pain at the site of injection.<ref name=AHFS2015/> It increases the risk of hospital-acquired Clostridioides difficile colitis about fourfold and thus is only recommended for use when other antibiotics are not appropriate.<ref name=Thomas>Template:Cite journal</ref><ref name=AHFS2015/> It appears to be generally safe in pregnancy.<ref name=AHFS2015/> It is of the lincosamide class and works by blocking bacteria from making protein.<ref name=AHFS2015/>

Clindamycin was first made in 1966 from lincomycin.<ref name=Sm1998>Template:Cite journal</ref><ref>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO22nd">Template:Cite book</ref> It is available as a generic medication.<ref name=Ric2015>Template:Cite book</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2022, it was the 147th most commonly prescribed medication in the United States, with more than 3Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Clindamycin is used primarily to treat anaerobic infections caused by susceptible anaerobic bacteria, including dental infections,<ref>Template:Cite journal</ref> and infections of the respiratory tract, skin, and soft tissue, and peritonitis.<ref name=RxList1>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In people 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.<ref name=RxList1/><ref name="Darley">Template:Cite journal</ref> Topical application of clindamycin phosphate can be used to treat mild to moderate acne.<ref name="Feldman">Template:Cite journal</ref><ref name="pmid31613567">Template:Cite journal</ref>

Acne

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Clindamycin phosphate topical solution

For the treatment of acne, in the long term, the combined use of topical clindamycin and benzoyl peroxide was similar to salicylic acid plus benzoyl peroxide.<ref name="pmid31613567" /><ref name=Sei2010/> Topical clindamycin plus topical benzoyl peroxide is more effective than topical clindamycin alone.<ref name="pmid31613567" /><ref name=Sei2010>Template:Cite journal</ref>

Susceptible bacteria

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.<ref name="Merck" />
• Anaerobic, Gram-negative rod-shaped bacteria, including some Bacteroides, Fusobacterium, and Prevotella, although resistance is increasing in Bacteroides fragilis.<ref>Template:Cite journal</ref>

Most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus influenzae and Moraxella) are resistant to clindamycin,<ref name="Merck" /><ref name="Bell">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> as are the facultative anaerobic Enterobacteriaceae.<ref name="Gold">Template:Cite book Template:Retrievedthrough Google Book Search.</ref> A notable exception is Capnocytophaga canimorsus, for which clindamycin is a first-line drug of choice.<ref>Template:Cite journal</ref>

The following represents MIC susceptibility data for a few medically significant pathogens.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Staphylococcus aureus: 0.016 μg/mL – >256 μg/mL
• Streptococcus pneumoniae: 0.002 μg/mL – >256 μg/mL
• Streptococcus pyogenes: <0.015 μg/mL – >64 μg/mL

D-test

File:D test.jpg

D-test

When testing a gram-positive culture for sensitivity to clindamycin, it is common to perform a "D-test" to determine if there is a sub-population of bacteria present with the phenotype known as Template:Not a typo. This phenotype of bacteria are resistant to the macrolide-lincosamide-streptogramin B group of antibiotics; however, the resistance mechanism is only induced by the presence of 14-membered ring macrolides, such as erythromycin. During a D-test, bacteria of the Template:Not a typo phenotype demonstrate in vitro erythromycin-induced in vitro resistance to clindamycin. This is because of the activity of the macrolide-inducible plasmid-encoded erm gene.<ref>Template:Cite journal</ref>

To perform a D-test, an agar plate is inoculated with the bacteria in question and two drug-impregnated disks (one with erythromycin, one with clindamycin) are placed 15–20 mm apart on the plate. If the area of inhibition around the clindamycin disk is D-shaped, the test result is positive. Despite the apparent susceptibility to clindamycin in the absence of erythromycin, a positive D-test precludes therapeutic use of clindamycin. This is because the erythromycin-inducible erm gene is prone to mutations causing the inducible activity to switch to constitutive (permanently switched on).<ref name="Macrolide-inducible resistance to c">Template:Cite journal</ref> This, in turn, may lead to the therapeutic failure of clindamycin.

If the area of inhibition around the clindamycin disk is circular, the test result is negative and clindamycin can be used.<ref name="Macrolide-inducible resistance to c"/>

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.<ref name=Lell2002>Template:Cite journal</ref><ref name="Griffith">Template:Cite journal</ref> Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.<ref name=Lell2002 /><ref name="Griffith" /> 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.<ref name="Dharia">Template:Cite journal</ref>

Other

Clindamycin may be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA).<ref name="Daum2007" /> 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.Template:Medical citation needed

While it has been used in intraabdominal infections, such use is generally not recommended due to resistance.<ref name=AHFS2015/>

Clindamycin is used in cases of suspected toxic shock syndrome,<ref name="Annane">Template:Cite journal</ref> 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 wall, and clindamycin, which is a powerful inhibitor of toxin synthesis. Both in vitro and in vivo studies have shown clindamycin reduces the production of exotoxins by staphylococci;<ref>Template:Cite journal</ref> it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref name="Lamont">Template:Cite journal</ref>

The combination of clindamycin and quinine is the standard treatment for severe babesiosis.<ref name="Homer">Template:Cite journal</ref>

Clindamycin may also be used to treat toxoplasmosis,<ref name="Merck" /><ref name="Pleyer">Template:Cite journal</ref><ref name="Jeddi">Template:Cite journal</ref> and, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.<ref>Template:Cite journal</ref>

Clindamycin, either applied to skin or taken by mouth, may also be used in hidradenitis suppurativa.<ref>Template:Cite journal</ref>

Side effects

Common adverse drug reactions associated with systemic clindamycin therapyTemplate:Sndfound in over 1% of peopleTemplate:Sndinclude: diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain or cramps and/or rash. High doses (both intravenous and oral) may cause a metallic taste. Common adverse drug reactions associated with topical formulationsTemplate:Sndfound in over 10% of peopleTemplate:Sndinclude: dryness, burning, itching, scaliness, or peeling of skin (lotion, solution); erythema (foam, lotion, solution); oiliness (gel, lotion). Additional side effects include contact dermatitis.<ref name="Rossi">Template:Cite book</ref><ref name="xl">Template:Cite journal</ref> Common side effectsTemplate:Sndfound in over 10% of peopleTemplate:Sndin vaginal applications include fungal infection.Template:Medical citation needed

RarelyTemplate:Snd in less than 0.1% of peopleTemplate:Snd clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzyme levels, renal dysfunction, cardiac arrest, and/or hepatotoxicity.<ref name="Rossi" />

Clostridioides difficile

Pseudomembranous colitis is a potentially lethal condition commonly associated with clindamycin, but which also occurs with other antibiotics.<ref name="Thomas" /><ref name="Starr">Template:Cite journal</ref> Overgrowth of Clostridioides 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.<ref name="Rossi" /><ref>Template:Cite journal</ref>

Pregnancy and breastfeeding

Use of clindamycin during pregnancy is generally considered safe.<ref>Template:Cite journal</ref>

Clindamycin is classified as compatible with breastfeeding by the American Academy of Pediatrics,<ref>Template:Cite journal</ref> however, the WHO categorizes it as "avoid if possible".<ref>Template:Cite book</ref> It is classified as L2 probably compatible with breastfeeding according to Medications and Mothers' Milk.<ref>Template:Cite book</ref> A 2009 review found it was likely safe in breastfeeding mothers, but did find one complication (hematochezia) in a breastfed infant which might be attributable to clindamycin.<ref>Template:Cite journal</ref> LactMed lists potentially negative gastrointestinal effects in babies whose mothers take it while breastfeeding but did not see that as justification to stop breastfeeding.<ref>Template:Cite journal</ref>

Interactions

Clindamycin may prolong the effects of neuromuscular-blocking drugs, such as succinylcholine and vecuronium.<ref name="Fogdall">Template:Cite journal</ref><ref name="al_Ahdal">Template:Cite journal</ref><ref name="Sloan">Template:Cite journal</ref> Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism<ref name=Bell/> and possible cross-resistance.Template:Medical citation needed

Chemistry

File:Clindamycin phosphate Structural Formula V2.svg

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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.<ref>Template:Cite journal</ref><ref name=Meyers>Template:Cite journal</ref> The synthesis of clindamycin was first announced by BJ Magerlein, RD Birkenmeyer, and F Kagan on the fifth Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in 1966.<ref>Template:Cite journal</ref> It has been on the market since 1968.<ref name="xl" />

Clindamycin is white or yellow powder that is very soluble in water.<ref name=":1">Template:Cite journal</ref> The topically used clindamycin phosphate is a phosphate-ester prodrug of clindamycin.<ref name="RxList" />

Mechanism of action

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Clindamycin mechanism

Clindamycin has a primarily bacteriostatic effect. At higher concentrations, it may be bactericidal.<ref name=":1" /> It is a bacterial protein synthesis inhibitor by inhibiting ribosomal translocation,<ref>Clindamycin University of Michigan. Retrieved 31 July 2009</ref> in a similar way to macrolides. It does so by binding to the rRNA of the bacterial 50S ribosome subunit, overlapping with the binding sites of the oxazolidinone, pleuromutilin, and macrolide antibiotics, among others.<ref name=Merck>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> The binding is reversible.<ref>Beauduy CE, Winston LG. Tetracyclines, Macrolides, Clindamycin, Chloramphenicol, Streptogramins, & Oxazolidinones. In: Katzung BG. eds. Basic & Clinical Pharmacology, 14e New York, NY: McGraw-Hill; .</ref> Clindamycin is more effective than lincomycin.<ref name=":1" />

The X-ray crystal structures of clindamycin bound to ribosomes (or ribosomal subunits) derived from Escherichia coli,<ref>Template:Cite journal</ref> Deinococcus radiodurans,<ref>Template:Cite journal</ref> and Haloarcula marismortui<ref>Template:Cite journal</ref> have been determined; the structure of the closely related antibiotic lincomycin bound to the 50S ribosomal subunit of Staphylococcus aureus has also been reported.<ref>Template:Cite journal</ref>

Society and culture

Economics

Clindamycin is available as a generic medication and is relatively inexpensive.<ref name=Ric2015/><ref name=Cun2009>Template:Cite book</ref>

Available forms

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Clindamycin capsules

Clindamycin preparations that are taken by mouth include capsules (containing clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate hydrochloride).<ref name=Lell2002 /> Oral suspension is not favored for administration of clindamycin to children, due to its extremely foul taste and odor. Clindamycin is formulated in a vaginal cream and as vaginal ovules for treatment of bacterial vaginosis.<ref name=Lamont/> It is also available for topical administration in gel form, as a lotion, and in a foam delivery system (each containing clindamycin phosphate) and a solution in ethanol (containing clindamycin hydrochloride) and is used primarily as a prescription acne treatment.<ref name="Cunliffe">Template:Cite journal</ref>

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.Template:Citation needed

Clindamycin is available as a generic drug, for both systemic (oral and intravenous) and topical use.<ref name=Lell2002 /> (The exception is the vaginal suppository, which is not available as a generic in the US<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>).

Veterinary use

The veterinary uses of clindamycin are quite similar to its human indications, and include treatment of osteomyelitis,<ref>(8 February 2005) "Osteomyelitis" Template:Webarchive, in Kahn, Cynthia M., Line, Scott, Aiello, Susan E. (ed.): The Merck Veterinary Manual, 9th ed., John Wiley & Sons. Template:ISBN. Retrieved 14 December 2007.</ref> skin infections, and toxoplasmosis, for which it is the preferred drug in dogs and cats.<ref>(8 February 2005) "Toxoplasmosis: Introduction" Template:Webarchive, in Kahn, Cynthia M., Line, Scott, Aiello, Susan E. (ed.): The Merck Veterinary Manual, 9th ed., John Wiley & Sons. Template:ISBN. Retrieved 14 December 2007.</ref> It can be used both by mouth and topically.<ref name=":1" /> A disadvantage is that bacterial resistance can develop fairly quickly.<ref name=":1" /> Gastrointestinal upset may also occur.<ref name=":1" /> Toxoplasmosis rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats.Template:Citation needed

External links

• Template:ClinicalTrialsGov