出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/04/16 02:35:21」(JST)
Systematic (IUPAC) name | |
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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 | DB01190 |
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 |
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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 Cleocin HCl® - Pfizer, Dalacin, Lincocin (Bangladesh), and 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.
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, 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]
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 min before clindamycin) to significantly increase the penetration of clindamycin into the skin, which may enhance efficacy.[12]
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,[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]
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: <0.015 μg/ml - >64 μg/ml [17]
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 MLSB, 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.[18]
Clindamycin may 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,[19] 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 clindamycin reduces the production of exotoxins by staphylococci;[20] it may also induce changes in the surface structure of bacteria that make them more sensitive to immune system attack (opsonization and phagocytosis).[21][22]
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.[23]
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.[24][25] Clindamycin should not be used as an antimalarial by itself, although it appears to be very effective as such, because of its slow action.[24][25] 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.[26]
The combination of clindamycin and quinine is the standard treatment for severe babesiosis.[27]
Clindamycin may also be used to treat toxoplasmosis,[13][28][29] and, in combination with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.[30]
Clindamycin preparations for oral administration include capsules (containing clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate hydrochloride).[24] 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.[23] 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.[7]
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.[31] 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[24] (The exception is the vaginal suppository, which is not available as a generic in the USA).[citation needed]
Common adverse drug reactions 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.[32][33]
Pseudomembranous colitis is a potentially lethal condition commonly associated with clindamycin, but which occurs with other antibiotics, as well.[2][34] 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.[32]
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.[32]
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.[35][36] 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.[37] It has been on the market since 1968.[33]
Clindamycin has a bacteriostatic effect. It is a bacterial protein synthesis inhibitor by inhibiting ribosomal translocation,[38] 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.[39]
Clindamycin may prolong the effects of neuromuscular-blocking drugs, such as succinylcholine and vecuronium.[40][41][42] 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.
The veterinary uses of clindamycin are quite similar to its human indications, and include treatment of osteomyelitis,[43] skin infections, and toxoplasmosis, for which it is the preferred drug in dogs and cats.[44] Toxoplasmosis rarely causes symptoms in cats, but can do so in very young or immunocompromised kittens and cats.
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リンク元 | 「抗菌薬」「クリンダマイシン」「CLDM」 |
拡張検索 | 「clindamycin palmitate hydrochloride」「clindamycin phosphate」「clindamycin hydrochloride」「clindamycin resistant Streptococcus pneumoniae」 |
Mechanism of action | Drugs | |
1 | Block cell wall synthesis by inhibition of peptidoglycan cross-linking | penicillin, ampicillin, ticarcillin, piperacillin, imipenem, aztreonam, cephalosporins |
2 | Block peptidoglycan synthesis | bacitracin, vancomycin, cycloserine |
3 | Disrupt bacterial/fungal cell membranes | polymyxins |
4 | Disrupt fungal cell membranes | amphotericin B, nystatin, fluconazole/azoles |
5 | Block nucleotide synthesis | sulfonamides, trimethoprim |
6 | Block DNA topoisomerases | quinolones |
7 | Block mRNA synthesis | rifampin |
8 | Block protein synthesis at 50S ribosomal subunit | chloramphenicol, erythromycin/macrolides, lincomycin, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid |
9 | Block protein synthesis at 30S ribosomal subunit | aminoglycosides, tetracyclines, spectinomycin ATuSi → あつし |
感染臓器・臨床診断 | 原因菌 | 投与期間(抗菌薬) |
髄膜炎 | インフルエンザ菌 | 7-10日 |
肺炎球菌 | 10-14日 | |
髄膜炎菌 | 7-10日 | |
GBS,腸内細菌,リステリア | 21日 | |
中耳炎 | <2 歳 | 10日 |
2 歳≦ | 5-7日 | |
咽頭炎 | A 群連鎖球菌 | 10日(ペニシリン系薬) |
5日(セフェム系薬) | ||
肺炎 | 肺炎球菌,インフルエンザ菌 | 解熱後3-4日 |
黄色ブドウ球菌 | 3-4週間 | |
マイコプラズマ,クラミジア | 10-21日 | |
腎臓、膀胱炎、腎盂腎炎 | 大腸菌,プロテウス,腸球菌 | 3日 |
14日 | ||
骨髄炎 | 黄色ブドウ球菌 | 21日 |
連鎖球菌,インフルエンザ菌 | 14日 |
骨 | 骨髄炎 | 4-6週 | |
耳鼻咽喉 | 中耳炎 | 5-7日 | |
副鼻腔炎 | 5-14日 | ||
A群溶連菌咽頭炎 | 10日 | ||
肺 | 肺炎 | 肺炎球菌 | 7-10日 or 解熱後3日間 |
インフルエンザ菌 | 10-14日 | ||
マイコプラズマ | 14日(7-10日) | ||
レジオネラ | 21日 | ||
肺化膿症 | 28-42日 | ||
心臓 | 感染性心内膜炎 | α連鎖球菌 | 2-4週 |
黄色ブドウ球菌 | 4-6週 | ||
消化管 | 腸炎 | 赤痢菌 | 3日 |
チフス | 14日(5-7日) | ||
パラチフス | |||
腹膜炎 | 特発性 | 5日 | |
二次性 | 10-14日 | ||
胆肝膵 | 肝膿瘍 | 細菌性 | 4-8週 |
アメーバ性 | 10日 | ||
尿路 | 膀胱炎 | 3日 | |
急性腎盂腎炎 | 14日(7-10日) | ||
急性腎盂腎炎・再発 | 6週 | ||
慢性前立腺炎 | 1-3ヶ月 | ||
髄腔 | 髄膜炎 | インフルエンザ菌 | 7-10日 |
髄膜炎菌 | |||
肺炎球菌 | 10-14日 | ||
リステリア | 21日 | ||
敗血症 | 敗血症 | コアグラーゼ陰性ブドウ球菌 | 5-7日 |
黄色ブドウ球菌 | 28日(14日) | ||
グラム陰性桿菌 | 14日(7-14日) | ||
カンジダ | 血液培養陰性化後, 14日 |
.