Clindamycin

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 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. 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. 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. • Staphylococcus aureus: 0.016 μg/mL – >256 μg/mL • Streptococcus pneumoniae: 0.002 μg/mL – >256 μg/mL • Streptococcus pyogenes: 64 μg/mL 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 . 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 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. 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). 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. Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action. Other Clindamycin may be useful in skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). 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. Clindamycin, either applied to skin or taken by mouth, may also be used in hidradenitis suppurativa. == Side effects ==

Common adverse drug reactions associated with systemic clindamycin therapyfound in over 1% of peopleinclude: 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 formulationsfound in over 10% of peopleinclude: 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 effectsfound in over 10% of peoplein vaginal applications include fungal infection. Rarely in less than 0.1% of people clindamycin therapy has been associated with anaphylaxis, blood dyscrasias, polyarthritis, jaundice, raised liver enzyme levels, renal dysfunction, cardiac arrest, and/or hepatotoxicity. 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. Compared to other antibiotics, clindamycin has a substantially higher risk of causing clinically significant C. difficile infection. Pregnancy and breastfeeding Use of clindamycin during pregnancy is generally considered safe. Clindamycin is classified as compatible with breastfeeding by the American Academy of Pediatrics, however, the WHO categorizes it as "avoid if possible". It is classified as L2 probably compatible with breastfeeding according to ''Medications and Mothers' Milk''. 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. LactMed lists potentially negative gastrointestinal effects in babies whose mothers take it while breastfeeding but did not see that as justification to stop breastfeeding. == 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 phosphate-ester prodrug of clindamycin. == Mechanism of action ==

Clindamycin has a primarily bacteriostatic effect. At higher concentrations, it may be bactericidal. 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. The binding is reversible. Clindamycin is more effective than lincomycin. Deinococcus radiodurans, and Haloarcula marismortui have been determined; the structure of the closely related antibiotic lincomycin bound to the 50S ribosomal subunit of Staphylococcus aureus has also been reported. == Society and culture ==

Economics Clindamycin is available as a generic medication and is relatively inexpensive. Available forms Clindamycin preparations that are taken by mouth include capsules (containing clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate hydrochloride). 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.). == 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. It can be used both by mouth and topically. A disadvantage is that bacterial resistance can develop fairly quickly. Gastrointestinal upset may also occur. Toxoplasmosis rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats. == References ==