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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/25 14:59:05」(JST)

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Amikacin (formerly Apothecon's Amikin) is an aminoglycoside antibiotic used to treat different types of bacterial infections. Amikacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[1]

Medical uses

Amikacin is most often used for treating severe, hospital-acquired infections with multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and Enterobacter. Serratia marcescens and Providencia stuartii are also included in the spectrum. Amikacin can also be used to treat non-tubercular mycobacterial infections and tuberculosis (if caused by sensitive strains) when first-line drugs fail to control the infection.

Amikacin may be combined with a beta-lactam antibiotic for empiric therapy for people with neutropenia and fever.

Liposomal amikacin for inhalation is currently in late stage clinical trials for the treatment of respiratory diseases, such as cystic fibrosis,^[2] Pseudomonas aeruginosa,^[3] non-tubercular mycobacterial infections^[4] and bronchiectasis.^[5]^[6]

Bacterial susceptibility data

Amikacin is usually used as a last-resort medication against multidrug-resistant bacteria. The following represents susceptibility data on a few medically significant microorganisms.

Pseudomonas aeruginosa - 0.5 μg/mL - 32 μg/mL
Pseudomonas aeruginosa (aminoglycoside-resistant) - 32 μg/mL - 64 μg/mL
Serratia marcescens - ≤0.25 μg/mL - 8 μg/mL
Serratia marcescens (multidrug-resistant) - 32 μg/mL

^[7]

Adverse effects

Side-effects of amikacin are similar to those of other aminoglycosides. Kidney damage and hearing loss are the most important effects. Because of this potential, blood levels of the drug and markers of kidney function (creatinine) may be monitored. Moreover, doses are adjusted specifically based upon serum Creatinine clearance in clinical settings.^{[citation needed]}

Administration

Amikacin may be administered once or twice a day but must be given by the intravenous or intramuscular route or via nebulization. There is no oral form available as amikacin is not absorbed orally. In people with kidney failure, dosage must be adjusted according to the creatinine clearance, usually by reducing the dosing frequency.

Resistance

Amikacin has high resistance against bacterial inactivation. It resists attacks by most bacterial inactivating enzymes. This is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA) moiety attached to N-3, which inhibits acetylation, phosphorylation, and adenylation in the distant amino sugar ring (C-2,C-3,C-4). To prevent the development of bacterial resistance to this antibiotic, its use is tightly regulated.

References

^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
^ "Randomized, open-label, active-controlled, multicenter study to assess the efficacy, safety and tolerability of Arikace™ in Cystic Fibrosis patients with chronic infection due to Pseudomonas aeruginosa" is a European Phase III clinical trial, being conducted across multiple sites in the EU, starting at the Royal Brompton Hospital, Department of Respiratory Medicine, in London. https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000441-20/GB
^ http://www.clinicaltrials.gov/ct2/show/NCT01315678
^ "A Randomized, Double-Blind, Placebo-Controlled Study of Liposomal Amikacin for Inhalation (Arikace™) in Patients With Recalcitrant Nontuberculous Mycobacterial Lung Disease" is a Phase II clinical trial in collaboration with the US National Institute of Allergy and Infectious Diseases. http://www.clinicaltrials.gov/ct2/show/NCT01315236
^ "A Placebo Controlled, Randomized, Parallel Cohort, Safety And Tolerability Study Of 2 Dose Levels Of Liposomal Amikacin For Inhalation (Arikace™) In Patients With Bronchiectasis Complicated By Chronic Infection Due To Pseudomonas Aeruginosa" Phase II (completed). http://www.clinicaltrials.gov/ct2/show/NCT00775138
^ "A Study to Determine the Safety and Tolerability of Arikace™ Versus Placebo in Patients Who Have Bronchiectasis" is a Phase II clinical trial (as [4]) completed in the UK. http://www.ukctg.nihr.ac.uk/trialdetails/NCT00775138
^ http://www.toku-e.com/Assets/MIC/Amikacin%20hydrate.pdf

Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. Review. PMID 10319086

UpToDate Contents

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1. アミノグリコシド aminoglycosides
2. グラム陰性桿菌性髄膜炎：治療 gram negative bacillary meningitis treatment
3. アミノグリコシド（非経口）の用量および投与 dosing and administration of parenteral aminoglycosides
4. 緑膿菌感染症に対する抗菌薬治療の原則 principles of antimicrobial therapy of pseudomonas aeruginosa infections
5. 成人におけるグラム陰性桿菌菌血症 gram negative bacillary bacteremia in adults

English Journal

Prevalence and characterization of methicillin susceptible Staphylococcus aureus ST398 isolates from retail foods.

Li G1, Wu C2, Wang X3, Meng J4.
International journal of food microbiology.Int J Food Microbiol.2015 Mar 2;196:94-7. doi: 10.1016/j.ijfoodmicro.2014.12.002. Epub 2014 Dec 11.
In this study, we explored the prevalence of Staphylococcus aureus (S. aureus) ST398 in retail foods and then investigated for their virulence and antimicrobial resistance genetic background. Fourteen out of 5103 (0.27%) samples were positive for methicillin susceptible S. aureus (MSSA) ST398. Resis
PMID 25528727

The microbiological quality of ready-to-eat salads in Turkey: A focus on Salmonella spp. and Listeria monocytogenes.

Gurler Z1, Pamuk S1, Yildirim Y2, Ertas N3.
International journal of food microbiology.Int J Food Microbiol.2015 Mar 2;196:79-83. doi: 10.1016/j.ijfoodmicro.2014.11.021. Epub 2014 Nov 29.
The microbiological safety of ready-to-eat (RTE) foods is of special concern as they are not exposed to further processing before consumption. In the present study, Listeria monocytogenes and Salmonella spp. were isolated from 15(6%) and 21(8%) samples respectively out of 261 RTE foods commercialize
PMID 25528536

Possible transfer of plasmid mediated third generation cephalosporin resistance between Escherichia coli and Shigella sonnei in the human gut.

Rashid H1, Rahman M2.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.Infect Genet Evol.2015 Mar;30:15-8. doi: 10.1016/j.meegid.2014.11.023. Epub 2014 Nov 26.
Choice of antibiotic for treatment of serious bacterial infection is rapidly diminishing by plasmid mediated transfer of antibiotic resistance. Here, we report a possible horizontal transfer of plasmid carrying third-generation-cephalosporin (TGC) resistance between Escherichia coli and Shigella son
PMID 25461693

Japanese Journal

Pharmacokinetic Variability of Amikacin After Once-Daily and Twice-Daily Dosing Regimen in Full-Term Neonates

Vucicevic Katarina,Rakonjac Zorica,Miljkovic Branislava [他]
Journal of pharmacological sciences 124(2), 138-143, 2014-02
NAID 40019992547

Device-Associated Nosocomial Infection Rates and Distribution of Antimicrobial Resistance in a Medical-Surgical Intensive Care Unit in Turkey

Tigen E. Tukenmez,Dogru A.,Koltka E.N.,Unlu C.,Gura M.
Japanese Journal of Infectious Diseases 67(1), 5-8, 2014
… With respect to Pseudomonas aeruginosa, 30.9% of the strains were resistant to ciprofloxacin, 23.3% to amikacin, 43.1% to ceftazidime, 19.1% to piperacillin-tazobactam, and 34.7% to imipenem. …
NAID 130003399232

Pulmonary nocardiosis in patients with connective tissue disease: A report of two cases

Hagiwara Shinya,Tsuboi Hiroto,Hagiya Chihiro,Yokosawa Masahiro,Hirota Tomoya,Ebe Hiroshi,Takahashi Hiroyuki,Ogishima Hiroshi,Asashima Hiromitsu,Kondo Yuya,Umeda Naoto,Suzuki Takeshi,Hitomi Shigemi,Matsumoto Isao,Sumida Takayuki
Intractable & Rare Diseases Research 3(1), 25-28, 2014
… The patient had difficulty tolerating trimethoprim/sulfamethoxazole, so she was switched to and successfully treated with imipenem/cilastatin and amikacin. …
NAID 130003397581

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★リンクテーブル★

リンク元	「アミノグリコシド系抗菌薬」「アミカシン」「AMK」
拡張検索	「amikacin sulfate」

「アミノグリコシド系抗菌薬」

Amikacin
Systematic (IUPAC) name
	(2S)-4-Amino-N-[(2S,3S,4R,5S)-5-amino-2-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,4S,5R,6R)-6-(aminomethyl)-3,4,5-trihydroxy-oxan-2-yl]oxy-3-hydroxy-cyclohexyl]-2-hydroxy-butanamide
Clinical data
Trade names	Generic (formerly Amikin)
AHFS/Drugs.com	monograph
MedlinePlus	a682661
Pregnancy cat.	D (AU) C (US)
Legal status	POM (UK) ℞-only (US)
Routes	Intramuscular, intravenous
Pharmacokinetic data
Protein binding	0-11%
Half-life	2-3 hours
Excretion	Renal
Identifiers
CAS number	37517-28-5
ATC code	D06AX12 J01GB06, S01AA21
PubChem	CID 37768
DrugBank	DB00479
ChemSpider	34635
UNII	84319SGC3C
KEGG	D02543
ChEBI	CHEBI:2637
ChEMBL	CHEMBL177
Chemical data
Formula	C22H43N5O13
Mol. mass	585.603 g/mol
	SMILES O=C(N[C@H]3[C@H](O[C@H]1O[C@@H]([C@@H](O)[C@H](N)[C@H]1O)CO)[C@@H](O)[C@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](N)C3)[C@@H](O)CCN;
	InChI InChI=1S/C22H43N5O13/c23-2-1-8(29)20(36)27-7-3-6(25)18(39-22-16(34)15(33)13(31)9(4-24)37-22)17(35)19(7)40-21-14(32)11(26)12(30)10(5-28)38-21/h6-19,21-22,28-35H,1-5,23-26H2,(H,27,36)/t6-,7+,8-,9+,10+,11-,12+,13+,14+,15-,16+,17-,18+,19-,21+,22+/m0/s1 ; Key:LKCWBDHBTVXHDL-RMDFUYIESA-N ;
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　　[★]

英: aminoglycoside antibiotic
関: 抗菌薬、アミノグリコシド系薬、アミノグリコシド

GOO. chapter.45

タンパク質合成阻害による抗菌薬は静菌的なのもが多いが、アミノグリコシド系抗菌薬は「殺菌的」に作用

構造

amino sugars linked to an aminocyclitol ring by glycosidic bonds (GOO.1155)
名前の通りアミノ基-NH₂を多数有しているため正電荷を帯びる

→経口吸収不良

→脳脊髄液に移行しにくい。

→腎排泄されやすい

動態

内服不可能→外来患者に使いにくい
細胞膜(内膜)の通過は膜電位ポテンシャルに依存している。ここが律速段階となる。　→　細胞内移行性悪

阻害、拮抗要素：二価陽イオン、高浸透圧、pHの低下、嫌気的条件

膿瘍など嫌気的条件、酸性の高浸透圧尿など細菌の膜電位ポテンシャルが低下する場合に薬効低下

作用機序

30Sリボソームに作用してタンパク質合成を阻害

1. 翻訳開始を阻害
2. 翻訳を停止させる
3. 誤ったアミノ酸を取り込ませる

異常蛋白が細胞膜に挿入され、膜の透過性を変えてさらにアミノグリコシド系抗菌薬の取り込みを促す

薬理作用

薬効は迅速。濃度依存的。
post-antibiotic effectがある。

抗菌薬の血漿濃度がminnimum inhibitory concentration以下になっても殺菌活性が残存。殺菌活性の残存時間は濃度依存的

抗菌スペクトル

広い

副作用

腎障害：近位尿細管の壊死変性。用量依存的
耳毒性：CN VIII障害。内耳の有毛細胞を破壊。用量依存的
神経・筋遮断作用：(稀であるが)神経筋遮断作用(およびこれによる無呼吸)を呈する。遮断作用はネオマイシンが一番強く、カナマイシン、アミカシン、ゲンタマイシン、トブラマイシンがこれに続く。通常、胸腔内、腹腔に大量投与した時に生じるが、静脈内、筋肉内、あるいは経口投与でも起こりうる。大抵の発作(神経筋接合部が遮断される発作)は麻酔薬やその他の神経筋接合部遮断薬の投与で生じる(←どういう意味？)。重症筋無力症の患者はアミノグリコシド系抗菌薬による神経筋接合部遮断作用を受けやすい。(GOO.1164)