Clindamycin

Medical uses

Clindamycin is used primarily to treat anaerobic infections caused by susceptible anaerobic bacteria, including dental infections, and infections of the respiratory tract, skin, and soft tissue, and peritonitis. 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. Topical application of clindamycin phosphate can be used to treat mild to moderate acne.

Acne

The use of clindamycin in conjunction with benzoyl peroxide is more effective in the treatment of acne than the use of either product by itself.

Clindamycin and adapalene in combination are also more effective than either drug alone, although adverse effects are more frequent.

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

The following represents MIC susceptibility data for a few medically significant pathogens.

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 macrolide-resistant subpopulation of bacteria present. This test is necessary because some bacteria express a phenotype known as MLS_B, in which susceptibility tests will indicate the bacteria are susceptible to clindamycin, but in vitro the pathogen displays inducible resistance.

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 and clindamycin should not be used due to the possibility of resistant pathogens and therapy failure. If the area of inhibition around the clindamycin disk is circular, the test result is negative and clindamycin can be used.

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

Other

Clindamycin may be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA); 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, 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; it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis).

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.

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

Clindamycin may also be used to treat toxoplasmosis, and, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.

Side effects

Common adverse drug reactions associated with systemic clindamycin therapy – found in over 1% of people – include: 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 formulations – found in over 10% of people – include: dryness, burning, itching, scaliness, or peeling of skin (lotion, solution); erythema (foam, lotion, solution); oiliness (gel, lotion). Additional side effects include contact dermatitis. Common side effects – found in over 10% of people – in vaginal applications include fungal infection.

Pseudomembranous colitis is a potentially lethal condition commonly associated with clindamycin, but which occurs with other antibiotics, as well. 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.

Rarely – in less than 0.1% of patients – clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzyme levels, renal dysfunction, cardiac arrest, and/or hepatotoxicity.

Interactions

Clindamycin may prolong the effects of neuromuscular-blocking drugs, such as succinylcholine and vecuronium. Its similarity to the mechanism of action of macrolides and chloramphenicol means they should not be given simultaneously, as this causes antagonism and possible cross-resistance.

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. 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. It has been on the market since 1968.

The topically used clindamycin phosphate is a certain phosphate ester of clindamycin.

Mechanism of action

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

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.

Cost

It is available as a generic medication and is not very expensive. The wholesale cost in the developing world is about 0.06 to 0.12 USD per pill. In the United States it costs about 2.70 USD a dose.

The wholesale price in UK is less than 5 pence per pill, however the RX system covers the cost for citizens. Canada and Mexico also have a similar cost, with average price of 4 cents per pill.

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 formulated in a vaginal cream and as vaginal ovules for treatment of bacterial vaginosis. 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.

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. 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 exception is the vaginal suppository, which is not available as a generic in the USA).

Clindamycin is marketed as generic and under trade names including Cleocin HCl, Dalacin, Lincocin (Bangladesh), Dalacin, and Clindacin. Combination products include Duac, BenzaClin, Clindoxyl and Acanya (in combination with benzoyl peroxide), and Ziana (with tretinoin).

Veterinary use

The veterinary uses of clindamycin are quite similar to its human indications, and include treatment of osteomyelitis, skin infections, and toxoplasmosis, for which it is the preferred drug in dogs and cats. Toxoplasmosis rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats.