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an antibiotic (trade name Azactam) used against severe infections; has minimal side effects (同)Azactam

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/27 12:28:49」(JST)

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Aztreonam (trade names Azactam injection, Cayston inhalation) is a synthetic monocyclic beta-lactam antibiotic (a monobactam), with the nucleus based on a simpler monobactam isolated from Chromobacterium violaceum. It was approved by the U.S. Food and Drug Administration (FDA) in 1986. It is resistant to some beta-lactamases, but is inactivated by extended-spectrum beta-lactamases.

Mechanism of action

Aztreonam is similar in action to penicillin. It inhibits mucopeptide synthesis in the bacterial cell wall, thereby blocking peptidoglycan crosslinking. It has a very high affinity for penicillin-binding protein 3 (PBP-3) and mild affinity for PBP-1a. Aztreonam binds the penicillin-binding proteins of gram-positive and anaerobic bacteria very poorly and is largely ineffective against them.^[1] Aztreonam is bactericidal but less so than some of the cephalosporins.

Spectrum of Bacterial Susceptibility and Resistance

Acinetobacter anitratus, Escherichia coli and Proteus mirabilis species are generally susceptible to Aztreonam, while some Pseudomonas aeruginosa, Staphylococci, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus hemolyticus and Xanthomonas maltophilia are resistant to Aztreonam. Furthermore, Aeromonas hydrophila, Citrobacter diversus, Enterobacter agglomerans, Haemophilus spp. and Streptococcus pyogenes have developed resistance to Aztreonam to varying degrees.^[2]

Indications and spectrum of activity

Aztreonam has strong activity against susceptible gram-negative bacteria, including Pseudomonas aeruginosa. It has no useful activity against gram-positive bacteria or anaerobes. It is known to be effective against a wide range of bacteria including Citrobacter, Enterobacter, E. coli, Haemophilus, Klebsiella, Proteus, and Serratia species.^[3]

Synergism between aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa has been suggested.^[4]

Aztreonam is often used in patients who are penicillin allergic or who can not tolerate aminoglycosides.

Administration

Aztreonam is poorly absorbed when given via the oral route, so it must be administered as an intravenous or intramuscular injection (trade name Azactam ), or inhaled (trade name Cayston) using an ultrasonic nebulizer. In the United States the FDA approved the inhalative form on February 22, 2010 for the suppression of Pseudomonas aeruginosa infections in patients with cystic fibrosis.^[5] It received conditional approval for administration in Canada and the European Union September 2009,^[5] and has been fully approved in Australia.^[6]

Common adverse effects

Reported side-effects include injection site reactions, rash, and rarely toxic epidermal necrolysis. Gastrointestinal side effects generally include diarrhea and nausea and vomiting. There may be drug-induced eosinophilia. Because of the un-fused beta-lactam ring unique to aztreonam, there is limited cross-reactivity between aztreonam and other beta-lactam antibiotics, and it is generally considered safe to admininister aztreonam to patients with hypersensitivity (allergies) to penicillins.^[1]

Aztreonam is considered Pregnancy category B.

References

^ ^a ^b AHFS DRUG INFORMATION 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006.
^ "Aztreonam spectrum of bacterial susceptibility and Resistance". http://www.toku-e.com/Upload/Products/PDS/20120618004526.pdf. Retrieved 15 May 2012.
^ Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc.. 2006.
^ Kobayashi, Y., Uchida, H., Kawakami Y. (1992). "Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood". J Antimicrob Chemother 30 (6): 871–872. doi:10.1093/jac/30.6.871. PMID 1289363.
^ ^a ^b Larkin, Catherine (February 22, 2010). "Gilead’s Inhaled Antibiotic for Lungs Wins Approval". BusinessWeek. http://www.businessweek.com/news/2010-02-22/gilead-s-inhaled-antibiotic-for-lungs-wins-approval-update1-.html. Retrieved 2010-03-05.
^ "FDA approves Gilead cystic fibrosis drug Cayston". BusinessWeek. February 23, 2010. http://www.businessweek.com/ap/financialnews/D9E237QG1.htm. Retrieved 2010-03-05.

External links

MedlinePlus DrugInfo uspdi-202078

UpToDate Contents

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1. ペニシリン-アレルギー患者：セフェム系、カルバペネム系、およびモノバクタム系の使用 penicillin allergic patients use of cephalosporins carbapenems and monobactams
2. グラム陰性桿菌性髄膜炎：治療 gram negative bacillary meningitis treatment
3. β-ラクタマーゼ阻害剤、カルバペネム系、およびモノバクタム系抗菌薬の併用 combination beta lactamase inhibitors carbapenems and monobactams
4. セファロスポリン-アレルギー患者：セファロスポリンおよび関連抗菌薬のその後の使用 cephalosporin allergic patients subsequent use of cephalosporins and related antibiotics
5. β-ラクタム系抗生物質：作用機序、耐性および有害作用 beta lactam antibiotics mechanisms of action and resistance and adverse effects

English Journal

The antimicrobial activity of mecillinam, nitrofurantoin, temocillin and fosfomycin and comparative analysis of resistance patterns in a nationwide collection of ESBL-producing Escherichia coli in Norway 2010-2011.

Zykov IN1,2, Sundsfjord A1,2, Småbrekke L3, Samuelsen Ø1,3.
Infectious diseases (London, England).Infect Dis (Lond).2016 Feb;48(2):99-107. doi: 10.3109/23744235.2015.1087648. Epub 2015 Sep 28.
BACKGROUND: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Norway has been steadily increasing during the last 10-15 years as part of a global pandemic. ESBL producers frequently express co-resistance to other important antimicrobial drug classes, limiting ther
PMID 26414659

Microbiology of healthcare-associated infections and the definition accuracy to predict infection by potentially drug resistant pathogens: a systematic review.

Cardoso T1, Almeida M2, Carratalà J3, Aragão I4, Costa-Pereira A5, Sarmento AE6, Azevedo L7.
BMC infectious diseases.BMC Infect Dis.2015 Dec 11;15(1):565.
BACKGROUND: Healthcare-associated infections (HCAI) represent up to 50 % of all infections among patients admitted from the community. The current review intends to provide a systematic review on the microbiological profile involved in HCAI, to compare it with community-acquired (CAI) and hospital-
PMID 26653533

Multi-year, multi-national survey of the incidence and global distribution of metallo-β-lactamase-producing Enterobacteriaceae and P. aeruginosa.

Kazmierczak KM1, Rabine S2, Hackel M2, McLaughlin RE3, Biedenbach DJ2, Bouchillon SK2, Sahm DF2, Bradford PA3.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2015 Dec 7. pii: AAC.02379-15. [Epub ahead of print]
Metallo-β-lactamases (MBLs) hydrolyze all classes of β-lactams except monobactams and are not inhibited by classic serine β-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study
PMID 26643349

Japanese Journal

In Vitro Antibiotic Susceptibility of Francisella tularensis Isolates from Japan

Hotta Akitoyo,Fujita Osamu,Uda Akihiko,Sharma Neekun,Tanabayashi Kiyoshi,Yamamoto Yoshie,Yamada Akio,Morikawa Shigeru
Japanese Journal of Infectious Diseases 66(6), 534-536, 2013
… The susceptibility to seven other β-lactams (aztreonam, cefotaxime, cefoxitin, ceftriaxone, cefuroxime, imipenem, and meropenem) varied among the isolates. …
NAID 130003390336

A Novel Selective Medium for the Isolation of Rothia aeria in Oral Cavities

Nebuka Kenichi,Tsuzukibashi Osamu
International Journal of Oral-Medical Sciences 12(2), 79-84, 2013
… RASM consists of sodium gluconate, tryptone,lablemco powder and aztreonam. …
NAID 130003386569

Break-point Checkerboard Plate 法が有用であった多剤耐性菌緑膿菌感染症合併血液透析患者の1症例

田蒔昌憲,脇野修,菅野義彦 [他],坂東和香,細谷幸司,井上秀二,徳山博文,吉田理,長谷川直樹,岩田敏,林松彦,林晃一,伊藤裕
日本透析医学会雑誌 = Journal of Japanese Society for Dialysis Therapy 45(9), 881-887, 2012-09-28
感染症は維持透析患者における頻度の高い死亡原因のひとつである．多剤耐性緑膿菌（multi-drug resistant <I>Pseudomonas aeruginosa</I>：MDRP）は有効な治療手段に乏しく，治療法の確立が急務とされている．今回われわれはBreak-point Checkerboard Plate（BCプレート）法を用いて抗菌薬の選択を行い良好な結果 …
NAID 10031123035

Related Pictures

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★リンクテーブル★

リンク元	「抗菌薬」「AZT」「アズトレオナム」

「抗菌薬」

Aztreonam
Systematic (IUPAC) name
	2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl) -2- {[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino} -2- oxoethylidene]amino}oxy)-2-methylpropanoic acid
Clinical data
Trade names	Azactam
AHFS/Drugs.com	monograph
Pregnancy cat.	B1 (Au), B (U.S.)
Legal status	℞-only (U.S.)
Routes	Intravenous, intramuscular, inhalation
Pharmacokinetic data
Bioavailability	100% (IM)
Protein binding	56%
Metabolism	hepatic (minor %)
Half-life	1.7 hours
Excretion	Renal
Identifiers
CAS number	78110-38-0
ATC code	J01DF01
PubChem	CID 54116
DrugBank	DB00355
ChemSpider	4674940
UNII	G2B4VE5GH8
KEGG	D00240
ChEBI	CHEBI:161680
ChEMBL	CHEMBL158
Chemical data
Formula	C13H17N5O8S2
Mol. mass	435.433 g/mol
	SMILES O=S(=O)(O)N2C(=O)[C@@H](NC(=O)C(=N\OC(C(=O)O)(C)C)/c1nc(sc1)N)[C@@H]2C;
	InChI InChI=1S/C13H17N5O8S2/c1-5-7(10(20)18(5)28(23,24)25)16-9(19)8(6-4-27-12(14)15-6)17-26-13(2,3)11(21)22/h4-5,7H,1-3H3,(H2,14,15)(H,16,19)(H,21,22)(H,23,24,25)/b17-8-/t5-,7-/m0/s1 ; Key:WZPBZJONDBGPKJ-VEHQQRBSSA-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

「AZT」

　　[★]

「アズトレオナム」

　　[★]

英: aztreonam、AZT
商: アザクタム, Azactam
関: 抗菌薬

[AHFS-0] AHFS DRUG INFORMATION 2006 (2006 ed.). American Society of Health-System Pharmacists. 2006.

[1] "Aztreonam spectrum of bacterial susceptibility and Resistance". http://www.toku-e.com/Upload/Products/PDS/20120618004526.pdf. Retrieved 15 May 2012.

[Mosby-2] Mosby's Drug Consult 2006 (16 ed.). Mosby, Inc.. 2006.

[3] Kobayashi, Y., Uchida, H., Kawakami Y. (1992). "Synergy with aztreonam and arbekacin or tobramycin against Pseudomonas aeruginosa isolated from blood". J Antimicrob Chemother 30 (6): 871–872. doi:10.1093/jac/30.6.871. PMID 1289363.

[BW1-4] Larkin, Catherine (February 22, 2010). "Gilead’s Inhaled Antibiotic for Lungs Wins Approval". BusinessWeek. http://www.businessweek.com/news/2010-02-22/gilead-s-inhaled-antibiotic-for-lungs-wins-approval-update1-.html. Retrieved 2010-03-05.

[5] "FDA approves Gilead cystic fibrosis drug Cayston". BusinessWeek. February 23, 2010. http://www.businessweek.com/ap/financialnews/D9E237QG1.htm. Retrieved 2010-03-05.

匿名

検索

案内

案内

aztreonam