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an antibacterial drug (trade names Rifadin and Rimactane) used to treat tuberculosis (同)Rifadin, Rimactane

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/18 02:18:42」(JST)

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Rifampicin (INN, BAN) /rɪˈfæmpəsɪn/ or rifampin (USAN) is a bactericidal antibiotic drug of the rifamycin group.^[4]

Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase.^[5] Rifampicin may be abbreviated R, RMP, RA, RF, or RIF (US).

In 1957, a soil sample from a pine forest on the French Riviera was brought for analysis to the Lepetit Pharmaceuticals research lab in Milan, Italy. There, a research group headed by Prof. Piero Sensi (1920-2013^[6]) and Dr. Maria Teresa Timbal (1925 - 1969) discovered a new bacterium. This new species appeared immediately of great scientific interest since it was producing a new class of molecules with antibiotic activity. Because Sensi, Timbal and the researchers were particularly fond of the French crime story Rififi (about a jewel heist and rival gangs),^[7] they decided to call these compounds "rifamycins". After two years of attempts to obtain more stable semisynthetic products, a new molecule with high efficacy and good tolerability was produced in 1959 and was named "rifampicin".

Rifampicin is also known as rifaldazine,^[8] RMP, rofact (in Canada), and rifampin in the United States. There are various types of rifamycins from which this is derived, but the rifampicin form, with a 4-methyl-1-piperazinaminyl group, is by far the most clinically effective. Rifampicin can also be derived from rifamycin S.^[1]

Rifampicin is an intensely red solid, and the small fraction which reaches body fluids is known for imparting a harmless red-orange color to the urine (and to a lesser extent, also sweat and tears) of users, for a few hours after a dose. Maximal concentrations in the blood are decreased by about a third when the antibiotic is taken with food.^[9]

Medical uses

Rifampicin was introduced in 1967,^[10] as a major addition to the cocktail-drug treatment of tuberculosis and inactive meningitis, along with pyrazinamide, isoniazid, ethambutol, and streptomycin ("PIERS"). It must be administered regularly daily for several months without break; otherwise, the risk of drug-resistant tuberculosis is greatly increased.^[10] In fact, this is the primary reason it is used in tandem with the four aforementioned drugs, particularly isoniazid.^[11] This is also the primary motivation behind directly observed therapy for tuberculosis.

Rifampicin resistance develops quickly during treatment, so monotherapy should not be used to treat these infections — it should be used in combination with other antibiotics.

Rifampicin is also used in the treatment of cholestatic pruritus.^[12]

Most doctors recommend taking rifampicin on an empty stomach with one glass (200ml/8 oz.) of water. It is generally taken either one hour before meals or two hours after meals. However, it is important to discuss how to take any medicine with your doctor.^[13]

Mycobacteria

Rifampicin is typically used to treat Mycobacterium infections, including tuberculosis and leprosy (Hansen's disease). It can be used to treat abscesses, as an uncommon complication of BCG vaccination for tuberculosis.^{[citation needed]}

No difference exists between a three- to four-month regimen of rifampicin and a six- to nine-month regimen for preventing active tuberculosis in those with HIV-negative latent tuberculosis.^[14] The quality of the evidence was, however, low.^[14]

With multidrug therapy used as the standard treatment of Hansen's disease, rifampicin is always used in combination with dapsone and clofazimine to avoid eliciting drug resistance.

Other bacteria and protozoans

Rifampicin is used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in combination with fusidic acid, including in difficult-to-treat infections such as osteomyelitis and prosthetic joint infections.^[15] It is also used in prophylactic therapy against Neisseria meningitidis (meningococcal) infection. Rifampicin is also recommended as an alternative treatment for infections with the tick-borne disease pathogens, Borrelia burgdorferi and Anaplasma phagocytophilum when treatment with doxycycline is contraindicated, such as in pregnant women or in patients with a history of allergy to tetracycline antibiotics.^[16]^[17]

It is also used to treat infections by Listeria species, Neisseria gonorrhoeae, Haemophilus influenzae, and Legionella pneumophila. For these nonstandard indications, sensitivity testing should be done (if possible) before starting rifampicin therapy.

The Enterobacteriaceae, and Acinetobacter and Pseudomonas species are intrinsically resistant to rifampicin.

Further, it has been used with amphotericin B in largely unsuccessful attempts to treat primary amoebic meningoencephalitis caused by Naegleria fowleri.

Rifampicin can be used as monotherapy for a few days as prophylaxis against meningitis, but resistance develops quickly during long-term treatment of active infections, so the drug is always used against active infections in combination with other antibiotics. Give 30 minute before meal or 2 hours after meal and antacids should be given at least one hour after meal.^[18]

Rifampicin is relatively ineffective against spirochetes, which has led to its use as a selective agent capable of isolating them ^[19]

Viruses

Rifampicin has some effectiveness against vaccinia virus.^[20]^[21]

Mechanism of action

Binding of rifampicin in the active site of RNA polymerase. Mutation of amino acids shown in red are involved in resistance to the antibiotic.

Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase.^[22]

Crystal structure data and biochemical data indicate that rifampicin binds to RNA polymerase at a site adjacent to the RNA polymerase active center and blocks RNA synthesis by physically blocking the formation of the phosphodiester bond in the RNA backbone, preventing extension of RNA products beyond a length of 2-3 nucleotides ("steric-occlusion" mechanism).^[23]^[24]

Resistance to rifampicin arises from mutations that alter residues of the rifampicin binding site on RNA polymerase, resulting in decreased affinity for rifampicin.^[24] Resistant mutations map to the rpoB gene, encoding RNA polymerase beta subunit.

Pathogen Susceptibility

The following represents minimum inhibitory concentration (MIC) data for a few medically significant pathogens:

Mycobacterium tuberculosis - 0.002 µg/mL - 64 µg/mL
Mycobacterium bovis - 0.125 µg/mL
Stapylococcus aureus (methicillin resistant) - ≤0.006 µg/mL - 256 µg/mL^[25]
Chlamydia pneumoniae - 0.005 µg/mL^[26]

Adverse effects

The most serious adverse effect is related to rifampicin's hepatotoxicity, and patients receiving it often undergo baseline and frequent liver function tests to detect liver damage.

Rifampicin is an effective liver enzyme-inducer, promoting the upregulation of hepatic cytochrome P450 enzymes (such as CYP2C9 and CYP3A4), increasing the rate of metabolism of many other drugs that are cleared by the liver through these enzymes. As a consequence, rifampicin can cause a range of adverse reactions when taken concurrently with other drugs.^[27] For instance, patients undergoing long-term anticoagulation therapy with warfarin have to be especially cautious and increase their dosage of warfarin accordingly.^[28] Failure to do so could lead to undertreating with anticoagulation, resulting in serious consequences of thromboembolism.

Upregulation of hepatic metabolism of hormones decreases their levels, and rifampicin can also in similar fashion reduce the efficacy of hormonal contraception, to the extent the unintended pregnancies have been reported among users of oral contraceptives taking rifampicin in even short courses (for example, as prophylaxis against exposure to bacterial meningitis).

The more common unwanted effects include fever, gastrointestinal disturbances, rashes, and immunological reactions. Taking rifampicin can cause certain bodily fluids, such as urine and tears, to become orange-red in color, a benign side effect which can be frightening if it is not expected and prepared for. This effect may also be used to monitor effective absorption of the drug (if drug color is not seen in the urine, the patient may wish to move the drug dose farther in time from food or milk intake). The discolorizion of sweat and tears is not directly noticeable, but sweat may stain light clothing orange, and tears may permanently stain soft contact lenses. Since rifampicin may be excreted in breast milk, breast feeding should be avoided while it is being taken.

Adverse effects include:

Hepatotoxic - hepatitis, liver failure in severe cases
Respiratory - breathlessness
Cutaneous - flushing, pruritus, rash, redness and watering of eyes
Abdominal - nausea, vomiting, abdominal cramps with or without diarrhea
Flu-like symptoms - with chills, fever, headache, arthralgia, and malaise, rifampin has good penetration into the brain, and this may directly explain some malaise and dysphoria in a minority of users.

Allergic reactions may occur to rifampicin. Signs of these include rash, itching, swelling of the tongue or throat, severe dizziness, and trouble breathing.^[29]

Pharmacokinetics

Orally administered rifampicin results in peak plasma concentrations in about two to four hours. 4-Aminosalicylic acid (another antituberculosis drug) significantly reduces absorption of rifampicin,^[30] and peak concentrations may be lower. If these two drugs must be used concurrently (which happens often in treatment of TB), they must be given separately with an interval of eight to 12 hours between administrations.

Rifampicin is easily absorbed from the gastrointestinal (GI) tract; its ester functional group is quickly hydrolyzed in the bile, and it is catalyzed by a high pH and substrate-specific esterases. After about six hours, almost all of the drug is deacetylated. Even in this deacetylated form, rifampin is still a potent antibiotic; however, it can no longer be reabsorbed by the intestines and it is subsequently eliminated from the body. Only about 7% of the administered drug will be excreted unchanged through the urine, though urinary elimination accounts for only about 30% of the drug excretion. About 60% to 65% is excreted through the feces.

The half-life of rifampicin ranges from 1.5 to 5.0 hours, though hepatic impairment will significantly increase it. Food consumption, though, inhibits absorption from the GI tract, and the drug is more quickly eliminated. When rifampicin is taken with a meal, peak blood concentration falls by 36%. Antacids do not affect absorption, however.^[9] The decrease in rifampin absorption with food is sometimes enough to noticeably affect urine color, which can be used as a marker for whether or not a dose of the drug has been effectively absorbed.

Distribution of the drug is high throughout the body, and reaches effective concentrations in many organs and body fluids, including the cerebrospinal fluid. Since the substance itself is red, this high distribution is the reason for the orange-red color of the saliva, tears, sweat, urine, and feces. About 60% to 90% of the drug is bound to plasma proteins.^[31]

Interactions

Rifampicin is an inducer of many enzymes of the cytochrome P450 superfamily, including CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5, and CYP3A7.^[32] Thus it will speed up the metabolism of any drug metabolized by any of these enzymes in the body. Other possible interactions which may not be listed include antiretroviral agents, everolimus, atorvastatin, rosiglitazone/pioglitazone, celecoxib, clarithromycin, caspofungin, and lorazepam.^[33]

Rifampicin is antagonistic to the effect of gentamicin and amikacin.

Preparations

Rifampicin is available in:

Bulgaria as Tubocin (by Actavis/Balkanpharma)
Romania as Sinerdol (Sicomed)
UK as Rifadin (Aventis), Rimactan (Sandoz), Rifater (a combination with isoniazid and pyrazinamide) (Aventis), Rifinah (a combination with isoniazid) (Aventis), and Rimactazid (a combination with isoniazid) (Sandoz)
U.S. as Rifadin (Aventis), Rifater (combination with isoniazid and pyrazinamide) (Aventis), Rimactane (Novartis)
France as Rifadine (Aventis)
India R-Cinex 600 (Lupin Limited)/Micox (a combination of rifampicin and isoniazid)
Australia as Rimycin (Alphapharm)
Egypt as Rimactan (Sandoz)
Germany as Eremfat (Riemser)

Use in biotechnology

Rifampicin inhibits bacterial RNA polymerase, thus it is commonly used to inhibit the synthesis of host bacterial proteins during recombinant protein expression in bacteria. Since the RNA encoding for the recombinant gene is usually transcribed from DNA by a viral T7 RNA polymerase, its expression is not affected by the antibiotic.

References

^ ^a ^b "US Patent 3963705" (PATENT). Google. US Patent Office. Retrieved 14 November 2014.
^ "Rifampicin". Chemical Safety Information from Intergovernmental Organizations. International Programme on Chemical Safety. Retrieved 14 November 2014.
^ "Rifampicin (CAS 13292-46-1)". Santa Cruz Biotechnology Product Block. Santa Cruz Biotechnology. Retrieved 14 November 2014.
^ Masters, Susan B.; Trevor, Anthony J.; Katzung, Bertram G. (2005). Katzung & Trevor's pharmacology. New York: Lange Medical Books/McGraw Hill, Medical Pub. Division. ISBN 0-07-142290-0.
^ Sensi P, Margalith P, Timbal MT (1959). "Rifomycin, a new antibiotic—preliminary report". Farmaco Ed Sci 14: 146–147.
^ http://archiviostorico.corriere.it/2013/agosto/10/chimico_che_salvo_molte_vite_co_0_20130810_63918b4e-017d-11e3-ae0c-005a4b618eb7.shtml
^ "When I Use a Word . . .I Mean It". British Medical Journal 1999;319(7215):972 (9 October). Retrieved 2009-07-10.
^ Moncalvo F, Moreo G (1966). "Ricerche cliniche preliminari sull'impiego di una nuova rifamicina orale (rifaldazina) nella terapia della tubercolosi polmonare (nota preventiva).". G Ital Mal Torace 20 (3): 120–31. PMID 5974175.
^ ^a ^b "Kinetics of Rifampin taken with food and with antacids" (PDF). Retrieved 2011-11-07.
^ ^a ^b Long, James W. (1991). Essential Guide to Prescription Drugs 1992. New York: HarperCollins Publishers. pp. 925–929. ISBN 0-06-273090-8.
^ Erlich, Henry, W Ford Doolittle, Volker Neuhoff, and et al. . Molecular Biology of Rifomycin. New York, NY: MSS Information Corporation, 1973. pp. 44-45, 66-75, 124-130.
^ Hofmann, AF (2002). "Rifampicin and treatment of cholestatic pruritus". Gut 2002;50:436–9 51 (5): 756–757. doi:10.1136/gut.51.5.756. PMC 1773428. PMID 12377823.
^ "rifampin oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD". WebMD. WebMD. Retrieved 13 November 2014.
^ ^a ^b Sharma, SK; Sharma, A; Kadhiravan, T; Tharyan, P (July 5, 2013). "Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB". The Cochrane database of systematic reviews 7: CD007545. doi:10.1002/14651858.CD007545.pub2. PMID 23828580.
^ Aboltins CA, Page MA, Buising KL et al. (June 2007). "Treatment of staphylococcal prosthetic joint infections with debridement, prosthesis retention and oral rifampicin and fusidic acid". Clinical Microbiology and Infection 13 (6): 586–591. doi:10.1111/j.1469-0691.2007.01691.x. PMID 17331125.
^ Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.; Halperin, John J.; Steere, Allen C.; Klempner, Mark S.; Krause, Peter J.; Bakken, Johan S.; Strle, Franc; Stanek, Gerold; Bockenstedt, Linda; Fish, Durland; Stephen Dumler, J.; Nadelman, Robert B. (1 November 2006). "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases 43 (9): 1089–1134. doi:10.1086/508667. PMID 17029130.
^ Thomas RG, Dumler SJ, Carlyon JA (August 2009). "Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis". Expert Reviews in Anti-Infection Therapies 7 (6): 709–722. doi:10.1586/eri.09.44. PMC 2739015. PMID 19681699.
^ "Rifampicin". Retrieved August 22, 2014.
^ Leschine, S. B., and E. Canale-Parola. "Rifampin as a selective agent for isolation of oral spirochetes." Journal of clinical microbiology 12.6 (1980): 792.
^ Charity JC, Katz E, Moss B (March 2007). "Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin". Virology 359 (1): 227–32. doi:10.1016/j.virol.2006.09.031. PMC 1817899. PMID 17055024.
^ Sodeik B, Griffiths G, Ericsson M, Moss B, Doms RW (February 1994). "Assembly of vaccinia virus: effects of rifampin on the intracellular distribution of viral protein p65". J. Virol. 68 (2): 1103–14. PMC 236549. PMID 8289340.
^ Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. (1965). "Effect of rifamycin on protein synthesis". Nature 207 (995): 417–8. doi:10.1038/207417a0. PMID 4957347.
^ Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A. (2001). "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase". Cell 104 (6): 901–12. doi:10.1016/S0092-8674(01)00286-0. PMID 11290327.
^ ^a ^b Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., Ebright, R.H. (2008). "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center". Proc Natl Acad Sci USA 105 (39): 14820–5. doi:10.1073/pnas.0802822105. PMC 2567451. PMID 18787125.
^ http://antibiotics.toku-e.com/antimicrobial_1018.html
^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC105936/
^ Collins, R Douglas. Atlas of Drug Reactions. New York, NY: ChurchillLivingstone, 1985. pp. 123.
^ Stockley, Ivan H. "Anticoagulant Drug Interactions." Drug Interactions. 3rd ed. Boston: Blackwell Scientific Publications, 1994. pp. 274-275.
^ "rifampin oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD". WebMD. WebMD. Retrieved 13 November 2014.
^ G Curci, A Ninni, A.D'Aleccio (1969) Atti Tavola Rotonda Rifampicina, Taormina, page 19. Edizioni Rassegna Medica, Lepetit, Milano
^ Hardman, Joel G., Lee E. Limbird, and Alfred G. Gilman, eds. "Rifampin." The Pharmacological Basis of Therapeutics. 10th ed. United States of America: The McGraw-Hill Companies, 2001. pp. 1277-1279.
^ "Division of Clinical Pharmacology | Indiana University Department of Medicine". Medicine.iupui.edu. 2011-09-27. Retrieved 2011-11-07.
^ Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (Aug 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurol Scand 118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004.x. PMID 18384456.

External links

PubPK - Rifampicin pharmacokinetics
Prescribing Information for RIFADIN by Sanofi-Aventis
U.S. National Library of Medicine: Drug Information Portal - Rifampicin
PDR.net Concise Monograph - Rifadin
[www.stridesarco.com/.../Strides_Corporate_Presentation_May_2011.pdf Agila - Rifampicin]

UpToDate Contents

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Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea.

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A 63-year old man had dysphagia for 4 months and was admitted to our hospital with sudden haematemesis. Computed tomography revealed an aberrant right subclavian artery (ARSA) aneurysm and free air inside the aneurysm. Arterio-oesophageal fistula was diagnosed, and an emergency operation was perform
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Japanese Journal

Occurrence of Multidrug-Resistant and Toxic-Metal Tolerant Enterococci in Fresh Feces from Urban Pigeons in Brazil

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Microbes and environments 27(2), 179-185, 2012-06-01
… Out of 120 isolates, no resistance was observed against penicillin and vancomycin, but was observed against gentamicin (55.8%), chloramphenicol (21.7%), tetracycline (13.3%), ciprofloxacin (8.4%) and rifampin (2.5%). …
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鶴田紀子,井上卓也,三砂範幸 [他]
西日本皮膚科 74(1), 10-14, 2012-02
NAID 40019205460

Related Pictures

★リンクテーブル★

リンク元	「抗菌薬」「急性尿細管間質性腎炎」「リファンピン」「リファマイシン」

「抗菌薬」

Rifampicin
Systematic (IUPAC) name
	(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-{(E)-[(4-methylpiperazin-1-yl)imino]methyl}-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(28),2,4,9,19,21,25(29),26-octaen-13-yl acetate
Clinical data
Trade names	Rifadin
AHFS/Drugs.com	International Drug Names
MedlinePlus	a682403
Licence data	US FDA:link
Pregnancy; category	AU: C; US: C (Risk not ruled out);
Legal status	AU: Prescription Only (S4); CA: ℞-only; UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral, IV
Pharmacokinetic data
Bioavailability	90 to 95% oral
Protein binding	80%
Metabolism	Hepatic and intestinal wall
Half-life	3-4 hours
Excretion	Urine (~30%), faeces (60-65%)
Identifiers
CAS Registry Number	13292-46-1
ATC code	J04AB02 QJ54AB02
PubChem	CID: 5360416
IUPHAR ligand	2765
DrugBank	DB01045
ChemSpider	10468813
UNII	VJT6J7R4TR
KEGG	D00211
ChEBI	CHEBI:28077
ChEMBL	CHEMBL374478
NIAID ChemDB	007228
Synonyms	5,6,9,17,19,21-Hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-[N-(4-methyl-1-piperazinyl)formimidoyl]-2,7-(epoxypentadeca[1,11,13]trienimino)-naphtho[2,1-b]furan-1,11(2H)-dione 21-acetate Rifamycin SV Rifaldazine
PDB ligand ID	RFP (PDBe, RCSB PDB)
Chemical data
Formula	C43H58N4O12
Molecular mass	822.94 g/mol
	SMILES CN1CCN(CC1)/N=C/c2c(O)c3c5C(=O)[C@@]4(C)O/C=C/[C@H](OC)[C@@H](C)[C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(\C)C(=O)Nc2c(O)c3c(O)c(C)c5O4;
	InChI InChI=1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20+/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1 ; Key:JQXXHWHPUNPDRT-WLSIYKJHSA-N ;
Physical data
Melting point	183 to 188 °C (361 to 370 °F)
Boiling point	1,004.42 °C (1,839.96 °F)
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　　[★]

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

「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

「リファンピン」

　　[★]

英: rifampin
関: リファンピシン; 抗菌薬

作用機序 PPC. 599t

バクテリアのDNA依存性RNAポリメラーゼと安定な複合体を形成しRNA合成を阻害

「リファマイシン」

　　[★]

英: rifamycin
ラ: rifamycinum
関: rifabutin rifampin rifapentine; リファマイシン系抗菌薬

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案内

rifampin