WordNet

an antibiotic (trade name Erythrocin or E-Mycin or Ethril or Ilosone or Pediamycin) obtained from the actinomycete Streptomyces erythreus; effective against many Gram-positive bacteria and some Gram-negative (同)Erythrocin, E-Mycin, Ethril, Ilosone, Pediamycin

PrepTutorEJDIC

enlisted man下士官兵

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/20 20:25:41」(JST)

wiki en

Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often prescribed for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including Mycoplasma and legionellosis. It was first marketed by Eli Lilly and Company, and it is today commonly known as EES (erythromycin ethylsuccinate, an ester prodrug that is commonly administered). It is also occasionally used as a prokinetic agent.

In structure, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desosamine), making it a compound very difficult to produce via synthetic methods.

Erythromycin is produced from a strain of the actinomycete Saccharopolyspora erythraea.

History[edit]

Abelardo B. Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate erythromycin from the metabolic products of a strain of Streptomyces erythreus (designation changed to "Saccharopolyspora erythraea") found in the samples.

Lilly filed for patent protection of the compound and U.S. patent 2,653,899 was granted in 1953. The product was launched commercially in 1952 under the brand name Ilosone (after the Philippine region of Iloilo where it was originally collected). Erythromycin was formerly also called Ilotycin.

In 1981, Nobel laureate (1965 in chemistry) and professor of chemistry at Harvard University (Cambridge, MA, USA) Robert B. Woodward (posthumously), along with a large number of members from his research group, reported the first stereocontrolled asymmetric chemical synthesis of erythromycin A.

The antibiotic clarithromycin was invented by scientists at the Japanese drug company Taisho Pharmaceutical in the 1970s as a result of their efforts to overcome the acid instability of erythromycin.

Scientists at Chugai Pharmaceuticals discovered an erythromycin-derived motilin agonist called mitemcinal that is believed to have strong prokinetic properties (similar to erythromycin) but lacking antibiotic properties. At the present time, erythromycin is commonly used off-label for gastric motility indications such as gastroparesis. If mitemcinal can be shown to be an effective a prokinetic agent, it would represent a significant advance in the GI field as treatment with this drug would not carry the risk of unintentional selection for antibiotic-resistant bacteria.

Synthesis[edit]

Over the three decades after the discovery of erythromycin A and its activity as an antimicrobial, many attempts were made to synthesize it in the laboratory. However, the presence of ten stereospecific carbons and several points of distinct substitution has made the total synthesis of erythromycin A a formidable task.^[1] Complete syntheses of erythromycins’ related structures and precursors such as 6- deoxyerythronolide B have been accomplished, giving way to possible syntheses of different erythromycins and other macrolide antimicrobials.^[2] However, Woodward did successfully complete the synthesis of erythromycin A.^[3]^[4]^[5] This total synthesis begins with (7) and (8). After being coupled, the resulting structure is subjected to a series of reactions, including hydrolysis and stereospecific aldolization. The resulting pure enone is then converted to the desired dithiadecalin product (9) through a series of reduction and oxidation reactions. (9) is then converted to both a ketone (10) and an aldehyde (11).

Available forms[edit]

Erythromycin is available in enteric-coated tablets, slow-release capsules, oral suspensions, ophthalmic solutions, ointments, gels, and injections.

Enteric coated Erythomycin capsule from Abbott Labs.

The following erythromycin combinations are available for oral dosage:^[6]

erythromycin base (capsules, tablets)
erythromycin estolate (capsules, oral suspension, tablets). This form is contraindicated during pregnancy.^[7]
erythromycin (oral suspension, tablets)
erythromycin stearate (oral suspension, tablets)

For injection the available combinations are:^[6]

erythromycin gluceptate
erythromycin lactobionate.

Brand names include Robimycin, E-Mycin, E.E.S. Granules, E.E.S.-200, E.E.S.-400, E.E.S.-400 Filmtab, Erymax, Ery-Tab, Eryc, Ranbaxy, Erypar, EryPed, Eryped 200, Eryped 400, Erythrocin Stearate Filmtab, Erythrocot, E-Base, Erythroped, Ilosone, MY-E, Pediamycin, Zineryt, Abboticin, Abboticin-ES, Erycin, PCE Dispertab, Stiemycine, Acnasol and Tiloryth.

Adverse effects[edit]

Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are very common because erythromycin is a motilin agonist.^[8] Because of this, erythromycin tends not to be prescribed as a first-line drug. However, erythromycin may be useful in treating gastroparesis due to this pro-motility effect. Intravenous erythromycin may also be used in endoscopy as an adjunct to clear gastric contents.

More serious side-effects include arrhythmia with prolonged QTc intervals including Torsades de pointes and reversible deafness. Allergic reactions range from urticaria to anaphylaxis. Cholestasis, Stevens–Johnson syndrome, and toxic epidermal necrolysis are some other rare side-effects that may occur.

Exposure to erythromycin (especially long courses at antimicrobial doses, and also through breastfeeding) has been linked to an increased probability of pyloric stenosis in young infants.^[9] Erythromycin used for feeding intolerance in young infants has not been associated with hypertrophic pyloric stenosis.^[9]

Erythromycin estolate has been associated with reversible hepatotoxicity in pregnant women in the form of elevated serum glutamic-oxaloacetic transaminase and is not recommended during pregnancy. Some evidence suggests similar hepatotoxicity in other populations.^[10]

It can also affect the central nervous system, causing psychotic reactions, nightmares and night sweats.^[11]

It may also alter the effectiveness of combined oral contraceptive pills because of its effect on the gut flora. Erythromycin is an inhibitor of the cytochrome P450 system, which means that it can have a rapid effect on levels of other drugs metabolised by this system, e.g., warfarin.

Mechanism of action[edit]

Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher concentrations,^[12] but the mechanism is not fully understood. By binding to the 50s subunit of the bacterial 70s rRNA complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited.^[12] Erythromycin interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex. Without this translocation, the A site remains occupied and, thus, the addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is inhibited. This interferes with the production of functionally useful proteins, which is the basis of this antimicrobial action.

Pharmacokinetics[edit]

Erythromycin is easily inactivated by gastric acid; therefore, all orally-administered formulations are given as either enteric-coated or more-stable salts or esters, such as erythromycin ethylsuccinate. Erythromycin is very rapidly absorbed, and diffuses into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where, during active phagocytosis, large concentrations of erythromycin are released.

Metabolism[edit]

Most of erythromycin is metabolised by demethylation in the liver. Its main elimination route is in the bile. There is little renal excretion. Erythromycin's elimination half-life is 1.6 hours.

Interactions[edit]

Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular, by isozymes of the CYP3A superfamily, CYP3A (Hunt et al., 1992). The activity of the CYP3A enzymes can be induced or inhibited by certain drugs (e.g. dexamethasone) which can cause it to affect the metabolism of many different drugs, e.g. erythromycin. If other CYP3A substrates — drugs that are broken down by CYP3A - such as simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor)—are taken concomitantly with erythromycin, levels of the substrates will increase, often causing adverse effects. A noted drug interaction involves erythromycin and simvastatin, resulting in increased simvastatin levels and the potential for rhabdomyolysis. Another group of CYP3A4 substrates are drugs used for migraine such as ergotamine and dihydroergotamine; their adverse effects may be more pronounced if erythromycin is associated.^[11] Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia, and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4.^[13] Hence, erythromycin should not be administered to people using these drugs, or drugs that also prolong the QT interval. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap). Theophylline, which is used mostly in asthma, is also contraindicated.

Erythromycin is not recommended when using clindamycin-containing products, even topical products such as Duac or BenzaClin. In general, the simultaneous use of two different erythromycin derivatives (such as clindamycin and Mitemcinal) should be avoided as drugs in this macrolide family possess a common mechanism of action.

Erythromycin-derived compounds[edit]

Ansamycin
Azithromycin / Zithromax / Zitromax / Sumamed
Carbomycin
Cethromycin
Clarithromycin / Biaxin
Dirithromycin / Dynabac
Mitemcinal
Oleandomycin
Roxithromycin / Rulid / Surlid / Roxid
Spiramycin
Telithromycin
Tylocine

Notes[edit]

^ Pal S (2006). "A journey across the sequential development of macrolides and ketolides related to erythromycin". Tetrahedron 62 (14): 3171–3200. doi:10.1016/j.tet.2005.11.064.
^ Evans D. A., Kim A. S. (1997). "Synthesis of 6-Deoxyerythronolide B. Implementation of a General Strategy for the Synthesis of Macrolide Antibiotics". Tetrahedron Lett. 38: 53–56. doi:10.1016/S0040-4039(96)02258-7.
^ Woodward R. B., Logusch E., Nambiar K. P., Sakan K., Ward D. E., Au-Yeung , Balaram P., Browne L. J., Card P. J. et al. (1981). "Asymmetric Total Synthesis of Erythromycin. 1. Synthesis of an Erythronolide A Seco Acid Derivative via Asymmetric Induction". J. Am. Chem. Soc. 103 (11): 3210–3213. doi:10.1021/ja00401a049.
^ Woodward R. B., Logusch E., Nambiar K. P., Sakan K., Ward D. E., Au-Yeung , Balaram P., Browne L. J., Card P. J. et al. (1981). "Asymmetric Total Synthesis of Erythromycin. 2. Synthesis of an Erythronolide A Lactone System". J. Am. Chem. Soc. 103 (11): 3213–3215. doi:10.1021/ja00401a050.
^ Woodward R. B., Logusch E., Nambiar K. P., Sakan K., Ward D. E., Au-Yeung , Balaram P., Browne L. J., Card P. J. et al. (1981). "Asymmetric Total Synthesis of Erythromycin. 3. Total Synthesis of Erythromycin". J. Am. Chem. Soc. 103 (11): 3215–3217. doi:10.1021/ja00401a051.
^ ^a ^b drugs.com > erythromycin (Oral route, Parenteral route) Retrieved on Jan 11, 2010
^ Sexually Transmitted Diseases Treatment Guidelines 2006 Centers for Disease Control and Prevention. MMWR 2006;55
^ Weber FH Jr, et. al (April 1993). "Erythromycin: a motilin agonist and gastrointestinal prokinetic agent". American Journal of Gastroenterology 88 (4): 485–90. PMID 8470625.
^ ^a ^b Maheshwai N (March 2007). "Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis?". Arch. Dis. Child. 92 (3): 271–3. doi:10.1136/adc.2006.110007. PMC 2083424. PMID 17337692.
^ McCormack WM, George H, Donner A, Kodgis LF, Albert S, Lowe EW, Kass EH (1997). "Hepatotoxicity of erythromycin estoate during pregnancy". Antimicrob Agents Chemother 12 (5): 630–5. doi:10.1128/AAC.12.5.630. PMC 429989. PMID 21610.
^ ^a ^b Erythromycin. Belgian Center for Pharmacotherapeutical Information. Retrieved July 20, 2008.
^ ^a ^b Katzung PHARMACOLOGY, 9e Section VIII. Chemotherapeutic Drugs Chapter 44. Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins
^ Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes. N Engl J Med 2004;351:1089-96.

References[edit]

British National Formulary "BNF 49" March 2005.
Mims C, Dockrell HM, Goering RV, Roitt I, Wakelin D, Zuckerman M. Chapter 33: Attacking the Enemy: Antimicrobial Agents and Chemotherapy: Macrolides. In: Medical Microbiology (3rd Edition). London: Mosby Ltd; 2004. p 489
Hunt,Ch.M., Watkins, P.B., Saenger, P., Stave, G.M., Barlascini, N., Watlington, Ch.O., Wright, J.T., Guzelian, P.S., (1992) Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol. Clinical Pharmacology and Therapeutics 51: 18-23

External links[edit]

Erythromycin bound to proteins in the PDB
U.S. Patent 2,653,899
E.E.S. (Erythromycin Ethylsuccinate) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 早産児における経腸栄養に対するアプローチ approach to enteral nutrition in the premature infant
2. 胃不全麻痺の治療 treatment of gastroparesis
3. クラミジア・トラコマチス感染の治療 treatment of chlamydia trachomatis infection
4. 紅色陰癬 erythrasma
5. びまん性汎細気管支炎 diffuse panbronchiolitis

English Journal

Prevalence and characterization of antibiotic resistant Enterococcus faecalis in French cheeses.

Jamet E, Akary E, Poisson MA, Chamba JF, Bertrand X, Serror P.SourceActilait, 419, route des champs laitiers, F-74 800 La Roche sur Foron, France.
Food microbiology.Food Microbiol.2012 Sep;31(2):191-8. Epub 2012 Mar 28.
Prevalence of enterococci and antibiotic resistance profiles of Enterococcus faecalis was analyzed in 126 French cheeses from retail stores. Forty-four percent of pasteurized or thermised-milk cheeses, and up to 92% of raw-milk cheeses contained detectable enterococci. A total of 337 antibiotic resi
PMID 22608223

Drug-drug interactions and cooperative effects detected in electrochemically driven human cytochrome P450 3A4.

Sadeghi SJ, Ferrero S, Di Nardo G, Gilardi G.SourceDepartment of Life Sciences and Systems Biology, University of Torino, 10123 Turin, Italy.
Bioelectrochemistry (Amsterdam, Netherlands).Bioelectrochemistry.2012 Aug;86:87-91. Epub 2012 Mar 13.
Inhibition of cytochrome P450-mediated drug metabolism by a concomitantly administered second drug is one of the major causes of drug-drug interactions in humans. The present study reports on the first electrochemically-driven drug-drug interactions of human cytochrome P450 3A4 probed with erythromy
PMID 22480862

Molecular epidemiologic analysis of Staphylococcus aureus isolated from four burn centers.

Chen X, Yang HH, Huangfu YC, Wang WK, Liu Y, Ni YX, Han LZ.SourceDepartment of Clinical Microbiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
Burns : journal of the International Society for Burn Injuries.Burns.2012 Aug;38(5):738-42. Epub 2012 Feb 21.
Staphylococcus aureus has been a major cause of hospital-acquired infections. Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since 1980s as an epidemiologic problem in hospitals. This old pathogen brings a new challenge to all physicians and bacteriologists. Hence, effective measures
PMID 22360963

Japanese Journal

Effect of penicillin G on the biliary excretion of cholephilic compounds in rats

FUKAMI Masako,TANKA Atsushi,TAKIKAWA Hajime
Journal of hepato-biliary-pancreatic sciences 18(5), 684-688, 2011-09-01
NAID 10029688455

発色酵素基質培地による Nocardia seriolae のα-グルコシダーゼ活性の検出と薬剤感受性の推定

ISMAIL Tamer Fawzy,竹下朗,梅田奈央子,伊丹利明,吉田照豊
魚病研究 46(2), 62-64, 2011-06-15
… All the α-glu-positive isolates (n = 27) were erythromycin (Em)-sensitive, and more than half of them (n = 18) were oxytetracycline (OTC)-resistant. …
NAID 10029368699

Clinical and microbiological analysis of beta hemolytic streptococci during 2006-2010 at Nagoya City University Hospital

市川麻里子,南正明,大橋実,脇本幸夫,松井秀之,長谷川忠男
Nagoya medical journal 51(4), 175-189, 2011-03-01
… In GAS and GGS, erythromycin and tetracycline resistant rates were approximately 30% and 50%, respectively. …
NAID 110008151189

Related Pictures

★リンクテーブル★

リンク元	「抗菌薬」「マクロライド系抗菌薬」「エリスロマイシン」「急性尿細管間質性腎炎」「EM」
拡張検索	「erythromycin lactobionate」「erythromycin stearate」

「抗菌薬」

Erythromycin
Systematic (IUPAC) name
	(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-; {[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-; 14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-; 5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-; 3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione
Clinical data
Trade names	E-mycin, Erythrocin
AHFS/Drugs.com	monograph
MedlinePlus	a682381
Pregnancy cat.	A (AU) B (US)
Legal status	Prescription Only (S4) (AU) POM (UK) ℞-only (US)
Routes	oral, iv, im, topical, ophthalmic eye drops
Pharmacokinetic data
Bioavailability	Depends on the ester type between 30% - 65%
Protein binding	90%
Metabolism	liver (under 5% excreted unchanged)
Half-life	1.5 hours
Excretion	bile
Identifiers
CAS number	114-07-8
ATC code	D10AF02 J01FA01 S01AA17 QJ51FA01
PubChem	CID 3255
IUPHAR ligand	1456
DrugBank	DB00199
ChemSpider	12041
UNII	63937KV33D
KEGG	D00140
ChEBI	CHEBI:42355
ChEMBL	CHEMBL532
Chemical data
Formula	C37H67NO13
Mol. mass	733.93 g/mol
	SMILES CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)O)C)C)O)(C)O;
	InChI InChI=1S/C37H67NO13/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-/m1/s1 ; Key:ULGZDMOVFRHVEP-RWJQBGPGSA-N ;
(what is this?) (verify)

　　[★]

英: antibacterial drug, antibacterial
関: 抗生剤、薬理学、抗菌薬一覧、抗細菌薬

first aid step 1 2006 p.165

定義

細菌/微生物に静菌作用、殺菌作用を示す物質。結果として、人において病原性を除去する目的で使用される。
このうち、微生物によって産生される物質を抗生物質と呼ぶ

作用機序による分類

細胞壁合成阻害：βラクタム系抗菌薬(ペニシリン系抗菌薬、セフェム系抗菌薬、モノバクタム系抗菌薬、カルバペネム系抗菌薬)
核酸合成阻害　：ニューキノロン系抗菌薬、メトロニダゾール
タンパク質合成阻害

30S：アミノグリコシド系抗菌薬、テトラサイクリン系抗菌薬
50S：マクロライド系抗菌薬、クリンダマイシン、クロラムフェニコール、ストレプトグラミン系抗菌薬、オキソゾリニドン系抗菌薬(リゾネリド)

代謝拮抗：サルファ剤(サルファメソキサゾール、トリメトプリム)

first aid step 1 2006 p.165

	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

薬物動態

濃度依存性：アミノグリコシド系抗菌薬、ニューロキノロン系抗菌薬
時間依存性：βラクタム系抗菌薬

治療期間

小児

尾内一信 ; 第 39 回日本小児感染症学会教育講演 2 小児感染症の抗菌薬療法 -耐性菌時代の適正使用-

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
中耳炎	2 歳≦	5-7日
咽頭炎	A 群連鎖球菌	10日(ペニシリン系薬)
咽頭炎	A 群連鎖球菌	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
腎臓、膀胱炎、腎盂腎炎	大腸菌，プロテウス，腸球菌	14日
骨髄炎	黄色ブドウ球菌	21日
骨髄炎	連鎖球菌，インフルエンザ菌	14日

主要な感染症の抗菌薬投与期間

感染レジマニュ p.27

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

ソース不明

シャント感染：黄色ブドウ球菌：頭蓋内デバイスの感染の場合、髄液培養陰性+10日間

妊婦に避けるべき抗菌薬

Antibiotics to avoid in pregnancy
Sulfonamides––kernicterus.
Aminoglycosides––ototoxicity.
Fluoroquinolones––cartilage damage.
Erythromycin––acute cholestatic hepatitis in mom

(and clarithromycin––embryotoxic).

Metronidazole––mutagenesis.
Tetracyclines––discolored teeth, inhibition of bone growth.
Ribavirin (antiviral)––teratogenic.
Griseofulvin (antifungal)––teratogenic.
Chloramphenicol––“gray baby.”
SAFE Moms Take Really Good Care.

使っても良い

YN.H-24

βラクタム系
エリスロマイシン、アジスロマイシン

参考

抗菌薬インターネットブック

まとまっていてよい

http://www.antibiotic-books.jp

抗菌薬一覧

「マクロライド系抗菌薬」

　　[★]

英: macrolide antibiotic macrolide antibiotics, macrolides, MLs
同: マクロライド系抗生物質　←厳密には違うが、多くの人が間違って使っている
関: 抗菌薬

特徴

抗菌スペクトルが広い
静菌的に作用
大きな環状構造を有する。14員環-16員環
タンパク質合成阻害薬
抗生物質としての作用の他に、抗炎症作用を有するらしい

炎症の抑制 ex.びまん性汎細気管支炎

構造

http://www.sigmaaldrich.com/life-science/life-science-catalog/product-catalog.html?TablePage=14572877
Macrolide antibiotics contain a many-membered lactone ring (14-membered rings for erythromycin and clarithromycin and a 15-membered ring for azithromycin) to which are attached one or more deoxy sugars. Clarithromycin differs from erythromycin only by methylation of the hydroxyl group at the 6 position, and azithromycin differs by the addition of a methyl-substituted nitrogen atom into the lactone ring. These structural modifications improve acid stability and tissue penetration and broaden the spectrum of activity.(GOO. chapter 46)

作用機序

50Sリボソームに結合してタンパク質合成を阻害

inhibit bacterial protein synthesis by reacting with the 50s ribosomal subunit and preventing the release of the uncharged tRNA.

薬理作用

動態

経口で吸収される

抗菌スペクトル

ペニシリンより広い抗菌スペクトル
グラム陽性球菌、グラム陰性球菌、グラム陰性桿菌、スピロヘータ、一部のリケッチア、ウイルス

適応

マイコプラズマ肺炎、クラミジア感染症、カンピロバクター腸炎、レジオネラ症
びまん性汎細気管支炎：14員環マクロライドのみ
URIs, pneumonias, STD

グラム陽性球菌(ペニシリンアレルギー), Mycoplasma, Legionella, Chlamydia, Neisseria

注意

禁忌

副作用

肝障害
消化器障害
QT延長、心室性不整脈

悪心、嘔吐、消化器の蠕動を促進

薬物相互作用

テオフィリン

喘息の治療薬。CYP3A4で代謝される。中毒域と治療域がちかいので注意する

マクロライド系抗菌薬

14員環

15員環

アジスロマイシン azithromycin

16員環

14員環 (ケトライド系抗菌薬)

テリスロマイシン telithromycin　→　厳密にはケトライド系

有効性 (SMB.147)

○：殺菌的、△静菌的

「エリスロマイシン」

　　[★]

英: erythromycin, EM
商: アイロタイシン、エリスロシン、エコリシン、エリコリ、E-Mycin, Ery-Tab, Ery-C, Ilosone, Eryc, Ilotycin
関: 抗菌薬

first aid step1 2006 p.141,143,144,144-145,165,166,169,170,173,178,208

分類

抗菌薬

マクロライド系抗菌薬

14員環マクロライド

特徴

ペニシリン過敏症の患者に対する第一選択となる
P450の阻害作用を持つので他の薬剤との相互作用に注意が必要。
耐性菌が多い。MRSAは100%、肺炎球菌は50%が耐性を持つ (SMB.157)

構造

作用機序

50Sに結合し、リボソームの動きを妨げることで、A siteのpeptidyl-tRNAをP siteに移動するのを妨げる？
inhibit protein synthesis by blocking translocation

抗菌スペクトル

IRE.166

グラム陽性球菌、細胞内寄生菌(マイコプラズマ・ニューモニエ、クラミジア・トラコマティス、クラミドフィラ・ニューモニエ)、スピロヘータ(Borrelia burddorferi)、グラム陰性菌(Bordetella pertussis、Bartonella henselae、Bartonella quintana、Haemophilus ducreyi)

動態

IRE.166

分布：組織移行性がよく、ほとんどの組織に移行する。中耳、前立腺にも移行する。中枢神経系、関節腔には移行しづらい。
排泄：肝排泄。胆汁中に排泄。血液透析、腹膜透析では除去されない。

適応

びまん性細気管支炎
USMLE：Legionella pneumonia

注意

禁忌

副作用

USMLE

Q book p.356 6

「急性尿細管間質性腎炎」

　　[★]

英: acute tubulointerstitial nephritis
同: 急性間質性腎炎 acute interstitial nephritis, AIN
関: 尿細管間質性腎炎

原因

薬剤性

antibiotics (lactams, sulfonamides, quinolones, vancomycin, erythromycin, minocycline, rifampin, ethambutol, acyclovir)
NSAIDs,COX-2阻害薬
利尿薬(thiazides, furosemide, triamterene)
抗てんかん薬(フェニトイン、フェノバルビタール、カルバマゼピン、バルプロ酸)
その他(カプトプリル、H2受容体阻害薬、プロトンポンプ阻害薬、mesalazine、indinavir、アロプリノール)

感染症

細菌(Streptococcus、Staphylococcus、Legionella、Salmonella、Brucella、Yersinia、Corynebacterium diphtheriae)
ウイルス(Epstein-Barr virus、cytomegalovirus、Hantavirus、polyomavirus、HIV)
その他(レプトスピラ、リケッチア、マイコプラズマ)

特発性

「EM」

　　[★]

「erythromycin lactobionate」

　　[★]

ラクトビオン酸エリスロマイシン、エリスロマイシンラクトビオン酸塩

関: erythromycin、erythromycin estolate、erythromycin ethylsuccinate、erythromycin stearate、Erythrosin

「erythromycin stearate」

　　[★] ステアリン酸エリスロマイシン

関: erythromycin、erythromycin estolate、erythromycin ethylsuccinate、erythromycin lactobionate、Erythrosin

[1] Pal S (2006). "A journey across the sequential development of macrolides and ketolides related to erythromycin". Tetrahedron 62 (14): 3171–3200. doi:10.1016/j.tet.2005.11.064.

[2] Evans D. A., Kim A. S. (1997). "Synthesis of 6-Deoxyerythronolide B. Implementation of a General Strategy for the Synthesis of Macrolide Antibiotics". Tetrahedron Lett. 38: 53–56. doi:10.1016/S0040-4039(96)02258-7.

[3] Woodward R. B., Logusch E., Nambiar K. P., Sakan K., Ward D. E., Au-Yeung , Balaram P., Browne L. J., Card P. J. et al. (1981). "Asymmetric Total Synthesis of Erythromycin. 1. Synthesis of an Erythronolide A Seco Acid Derivative via Asymmetric Induction". J. Am. Chem. Soc. 103 (11): 3210–3213. doi:10.1021/ja00401a049.

[4] Woodward R. B., Logusch E., Nambiar K. P., Sakan K., Ward D. E., Au-Yeung , Balaram P., Browne L. J., Card P. J. et al. (1981). "Asymmetric Total Synthesis of Erythromycin. 2. Synthesis of an Erythronolide A Lactone System". J. Am. Chem. Soc. 103 (11): 3213–3215. doi:10.1021/ja00401a050.

[5] Woodward R. B., Logusch E., Nambiar K. P., Sakan K., Ward D. E., Au-Yeung , Balaram P., Browne L. J., Card P. J. et al. (1981). "Asymmetric Total Synthesis of Erythromycin. 3. Total Synthesis of Erythromycin". J. Am. Chem. Soc. 103 (11): 3215–3217. doi:10.1021/ja00401a051.

[drugs.com-6] rugs.com > erythromycin (Oral route, Parenteral route) Retrieved on Jan 11, 2010

[7] Sexually Transmitted Diseases Treatment Guidelines 2006 Centers for Disease Control and Prevention. MMWR 2006;55

[pmid8470625-8] Weber FH Jr, et. al (April 1993). "Erythromycin: a motilin agonist and gastrointestinal prokinetic agent". American Journal of Gastroenterology 88 (4): 485–90. PMID 8470625.

[pmid17337692-9] Maheshwai N (March 2007). "Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis?". Arch. Dis. Child. 92 (3): 271–3. doi:10.1136/adc.2006.110007. PMC 2083424. PMID 17337692.

[10] McCormack WM, George H, Donner A, Kodgis LF, Albert S, Lowe EW, Kass EH (1997). "Hepatotoxicity of erythromycin estoate during pregnancy". Antimicrob Agents Chemother 12 (5): 630–5. doi:10.1128/AAC.12.5.630. PMC 429989. PMID 21610.

[BCFI-11] Erythromycin. Belgian Center for Pharmacotherapeutical Information. Retrieved July 20, 2008.

[ReferenceA-12] Katzung PHARMACOLOGY, 9e Section VIII. Chemotherapeutic Drugs Chapter 44. Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins

[13] Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes. N Engl J Med 2004;351:1089-96.



Systematic (IUPAC) name
(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6- {[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}- 14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)- 5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}- 3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione
Clinical data
Trade names	E-mycin, Erythrocin
AHFS/Drugs.com	monograph
MedlinePlus	a682381
Pregnancy cat.	A (AU) B (US)
Legal status	Prescription Only (S4) (AU) POM (UK) ℞-only (US)
Routes	oral, iv, im, topical, ophthalmic eye drops
Pharmacokinetic data
Bioavailability	Depends on the ester type between 30% - 65%
Protein binding	90%
Metabolism	liver (under 5% excreted unchanged)
Half-life	1.5 hours
Excretion	bile
Identifiers
CAS number	114-07-8^Y
ATC code	D10AF02 J01FA01 S01AA17 QJ51FA01
PubChem	CID 3255
IUPHAR ligand	1456
DrugBank	DB00199
ChemSpider	12041^Y
UNII	63937KV33D^Y
KEGG	D00140^Y
ChEBI	CHEBI:42355^Y
ChEMBL	CHEMBL532^Y
Chemical data
Formula	C₃₇H₆₇NO₁₃
Mol. mass	733.93 g/mol
SMILES CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)O)C)C)O)(C)O
InChI InChI=1S/C37H67NO13/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-/m1/s1^Y Key:ULGZDMOVFRHVEP-RWJQBGPGSA-N^Y
Y (what is this?) (verify)

匿名

検索

案内

erythromycin

WordNet

PrepTutorEJDIC

Wikipedia preview

wiki en

Contents

History[edit]

Synthesis[edit]

Available forms[edit]

Adverse effects[edit]

Mechanism of action[edit]

Pharmacokinetics[edit]

Metabolism[edit]

Interactions[edit]

Erythromycin-derived compounds[edit]

Notes[edit]

References[edit]

External links[edit]

UpToDate Contents

English Journal

Japanese Journal

Related Links

Related Pictures

★リンクテーブル★

「抗菌薬」

定義

作用機序による分類

薬物動態

治療期間

小児

主要な感染症の抗菌薬投与期間

ソース不明

妊婦に避けるべき抗菌薬

使っても良い

参考

抗菌薬一覧

「マクロライド系抗菌薬」

特徴

構造

作用機序

薬理作用

動態

抗菌スペクトル

適応

注意

禁忌

副作用

マクロライド系抗菌薬

14員環

15員環

16員環

14員環 (ケトライド系抗菌薬)

有効性 (SMB.147)

「エリスロマイシン」

分類

特徴

構造

作用機序

抗菌スペクトル

動態

適応

注意

禁忌

副作用

USMLE

「急性尿細管間質性腎炎」

原因

「EM」

「erythromycin lactobionate」

「erythromycin stearate」