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Imipenem (Primaxin) is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in 1980.^[1] It was the first member of the carbapenem class of antibiotics. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria,^[2] thus play a key role in the treatment of infections not readily treated with other antibiotics.^[3]

It was discovered via a lengthy trial-and-error search for a more stable version of the natural product thienamycin, which is produced by the bacterium Streptomyces cattleya. Thienamycin has antibacterial activity, but is unstable in aqueous solution, so impractical to administer to patients.^[4] Imipenem has a broad spectrum of activity against aerobic and anaerobic, Gram-positive and Gram-negative bacteria.^[5] It is particularly important for its activity against Pseudomonas aeruginosa and the Enterococcus species. It is very active against MRSA, however.

Mechanism of action

Imipenem acts as an antimicrobial through inhibiting cell wall synthesis of various Gram-positive and Gram-negative bacteria. It remains very stable in the presence of β-lactamase (both penicillinase and cephalosporinase) produced by some bacteria, and is a strong inhibitor of β-lactamases from some Gram-negative bacteria that are resistant to most β-lactam antibiotics.

Spectrum of bacterial susceptibility and resistance

Acinetobacter anitratus, Acinetobacter calcoaceticus, Actinomyces odontolyticus, Aeromonas hydrophila, Bacteroides distasonis, Bacteroides uniformis, and Clostridium perfringens are generally susceptible to imipenem, while Acinetobacter baumannii, some Acinetobacter spp., Bacteroides fragilis, and Enterococcus faecalis have developed resistance to imipenem to varying degrees. Not many species are resistant to imipenem except Pseudomonas aeruginosa (Oman) and Stenotrophomonas maltophilia.^[6]

Coadministration with cilastatin

Imipenem is rapidly degraded by the renal enzyme dehydropeptidase 1 when administered alone, and is always coadministered with cilastatin to prevent this inactivation.^{[citation needed]}

Adverse effects

Common adverse drug reactions are nausea and vomiting. People who are allergic to penicillin and other β-lactam antibiotics should take caution if taking imipenem, as cross-reactivity rates are low. At high doses, imipenem is seizurogenic.^{[citation needed]}

References

^ U.S. Patent 4,194,047
^ Clissold, SP; Todd, PA; Campoli-Richards, DM (Mar 1987). "Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.". Drugs. 33 (3): 183–241. doi:10.2165/00003495-198733030-00001. PMID 3552595.
^ Vardakas, KZ; Tansarli, GS; Rafailidis, PI; Falagas, ME (Dec 2012). "Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis.". The Journal of antimicrobial chemotherapy. 67 (12): 2793–803. doi:10.1093/jac/dks301. PMID 22915465.
^ Kahan, FM; Kropp, H; Sundelof, JG; Birnbaum, J (Dec 1983). "Thienamycin: development of imipenen-cilastatin.". The Journal of antimicrobial chemotherapy. 12 Suppl D: 1–35. doi:10.1093/jac/12.suppl_d.1. PMID 6365872.
^ Kesado, Tadataka; Hashizume, Terutaka; Asahi, Yoshinari (1980). "Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics". Antimicrobial Agents and Chemotherapy. 17 (6): 912–7. doi:10.1128/aac.17.6.912. PMC 283902. PMID 6931548.
^ "Imipenem spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 4 May 2012.

External links

Imipenem bound to proteins in the PDB

UpToDate Contents

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1. 嚢胞性線維腺症：呼吸器症状が急性増悪した場合の治療cystic fibrosis treatment of acute pulmonary exacerbations [show details]
… For P. aeruginosa, antibiotic combinations include piperacillin-tazobactam, ceftazidime, imipenem-cilastatin, or meropenem (or ticarcillin-clavulanate, where available) plus one of the following: tobramycin …
2. 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 [show details]
…100 studies that compared imipenem to a non-carbapenem antibiotic, imipenem use was associated with an excess of 4 seizures per 1000 patients treated . CNS toxicity with imipenem is especially evident in …
3. 成人における確定診断を得られていない低血圧やショックの評価および初期アプローチevaluation of and initial approach to the adult patient with undifferentiated hypotension and shock [show details]
…beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate) or a carbapenem (eg, imipenem or meropenem). If Pseudomonas is likely, vancomycin should be combined with two antipseudomonal…
4. 基質特異性拡張型β-ラクタマーゼextended spectrum beta lactamases [show details]
…extended-spectrum beta-lactamase (ESBL)-producing organisms are carbapenems (imipenem, meropenem, doripenem, and ertapenem). We use meropenem or imipenem for most ESBL infections. Ertapenem is an acceptable option in …
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 [show details]
…antibiotics (particularly penicillins, fourth generation cephalosporins, and imipenem) may cause seizures . CNS toxicity of imipenem correlates with high doses, renal dysfunction, or underlying CNS disease…

English Journal

First National Survey of Antibiotic Susceptibility of the Bacteroides fragilis Group: Emerging Resistance to Carbapenems in Argentina.

Fernández-Canigia L, Litterio M, Legaria MC, Castello L, Predari SC, Di Martino A, Rossetti A, Rollet R, Carloni G, Bianchini H, Cejas D, Radice M, Gutkind G; the Anaerobe Surveillance Team.SourceAddress correspondence to Liliana Fernández-Canigia, lfcanigia@labdl.com.ar.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2012 Mar;56(3):1309-1314. Epub 2012 Jan 9.
The antibiotic susceptibility rates of 363 clinical Bacteroides fragilis group isolates collected from 17 centers in Argentina during the period from 2006 to 2009 were as follows: piperacillin-tazobactam, 99%; ampicillin-sulbactam, 92%; cefoxitin, 72%; tigecycline, 100%; moxifloxacin, 91%; and clind
PMID 22232282

Hydrolysis Spectrum Extension of CMY-2-Like β-Lactamases Resulting from Structural Alteration in the Y-X-N Loop.

Dahyot S, Mammeri H.SourceAddress correspondence to Hedi Mammeri, mammeri.hedi@chu-amiens.fr.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2012 Mar;56(3):1151-6. Epub 2012 Jan 9.
The Citrobacter freundii isolate CHA, which was responsible for postoperative peritonitis after 10 days of cefepime therapy, displayed a phenotype of resistance consistent with extended-spectrum AmpC (ESAC) β-lactamase. The chromosome-borne bla(AmpC-CHA) gene was amplified and sequenced, revealing
PMID 22232281

In Vitro Antibacterial Activity of the Ceftazidime-Avibactam (NXL104) Combination against Pseudomonas aeruginosa Clinical Isolates.

Levasseur P, Girard AM, Claudon M, Goossens H, Black MT, Coleman K, Miossec C.SourceAddress correspondence to C. Miossec, miossec.christine@gmail.com.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2012 Mar;56(3):1606-8. Epub 2012 Jan 3.
The β-lactamase inhibitor avibactam (NXL104) displays potent inhibition of both class A and C enzymes. The in vitro antibacterial activity of the combination ceftazidime-avibactam was evaluated against a clinical panel of Pseudomonas aeruginosa isolates. Avibactam offered efficient protection from
PMID 22214778

Japanese Journal

Prediction of the Stability of Imipenem in Intravenous Mixtures

Yoshida Miyako,Takasu Yuko,Shimizu Kaori 他
Chemical and pharmaceutical bulletin 61(1), 1-7, 2013-01-00
NAID 40019536345

脾動脈瘤切迫破裂に対する塞栓術後に肝脾膿瘍を合併した感染性心内膜炎急性心不全症例

菊地信介,赤坂伸之,光部啓次郎,福山貴久,内田大貴,小久保拓,古屋敦宏,内田恒,東信良,稲葉雅史,笹嶋唯博
心臓 44(4), 479-483, 2012-04-00
… 抗生物質は経験的にimipenem/cilastatin+gentamicinを投与したが、炎症反応が改善傾向になくvancomycin+gentamicinに変更した。 …
NAID 120004724327

Antibiotic Resistance and Extended-Spectrum β-Lactamases in Isolated Bacteria from Seawater of Algiers Beaches (Algeria)

ALOUACHE SOUHILA,KADA MOHAMED,MESSAI YAMINA,ESTEPA VANESA,TORRES CARMEN,BAKOUR RABAH
Microbes and environments 27(1), 80-86, 2012-03-01
… The most significant resistance rates were observed for amoxicillin and ticarcillin, whereas they were relatively low for ceftazidime, cefotaxime and imipenem. … Thirty-four bacteria resistant to imipenem (n=14) or cefotaxime (n=20) were identified as Pseudomonas aeruginosa (n=15), Pseudomonas fluorescens (7), Stenotrophomonas maltophilia (4), Burkholderia cepacia (2), Bordetella sp. …
NAID 10030122942

Related Pictures

Zienam: Zienam Injection | Buy Imipenem 500Mg & Cilastatin 500Mg Injection Reasonable Cardinal Glass Imipenem+Cilastatina amp caja x 10 | Bioncomedica Imipenem Glomed I.V Imipenem-Cilastatin Intravenous : Uses, Side Effects, Interactions, Pictures, Warnings lmipenem IMIPENEM ION | Laboratorio Ion

★リンクテーブル★

リンク元	「抗菌薬」「イミペネム」
拡張検索	「imipenem hydrate」

「抗菌薬」

Imipenem
Systematic (IUPAC) name
	(5R,6S)-6-[(1R)-1-hydroxyethyl]-3-({2-[(iminomethyl)amino]ethyl}thio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Clinical data
Trade names	Primaxin
AHFS/Drugs.com	International Drug Names
MedlinePlus	a686013
Pregnancy; category	AU: B3; US: C (Risk not ruled out); ;
Routes of; administration	IM, IV
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Protein binding	20%
Metabolism	Renal
Biological half-life	38 minutes (children), 60 minutes (adults)
Excretion	Urine (70%)
Identifiers
CAS Number	74431-23-5
ATC code	J01DH51 (WHO)
PubChem	CID 5282372
DrugBank	DB01598
ChemSpider	4445535
UNII	71OTZ9ZE0A
KEGG	D00206
ChEBI	CHEBI:51799
ChEMBL	CHEMBL43708
Chemical data
Formula	C12H17N3O4S
Molar mass	299.347 g/mol
	SMILES O=C(O)/C1=C(\SCC/N=C/N)C[C@H]2N1C(=O)[C@@H]2[C@H](O)C.O ;
	InChI InChI=1S/C12H17N3O4S.H2O/c1-6(16)9-7-4-8(20-3-2-14-5-13)10(12(18)19)15(7)11(9)17;/h5-7,9,16H,2-4H2,1H3,(H2,13,14)(H,18,19);1H2/t6-,7-,9-;/m1./s1 ; Key:GSOSVVULSKVSLQ-JJVRHELESA-N ;
(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

「イミペネム」

　　[★]

英: imipenem
商: イミスタン、イミペナーム、イミペネム・シラスタチン、インダスト、チエクール、チエナム、チエペネム
化: イミペネム水和物 imipenem hydrate

「imipenem hydrate」

　　[★]

イミペネム水和物

関: imipenem

[1] U.S. Patent 4,194,047

[2] Clissold, SP; Todd, PA; Campoli-Richards, DM (Mar 1987). "Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.". Drugs. 33 (3): 183–241. doi:10.2165/00003495-198733030-00001. PMID 3552595.

[3] Vardakas, KZ; Tansarli, GS; Rafailidis, PI; Falagas, ME (Dec 2012). "Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis.". The Journal of antimicrobial chemotherapy. 67 (12): 2793–803. doi:10.1093/jac/dks301. PMID 22915465.

[4] Kahan, FM; Kropp, H; Sundelof, JG; Birnbaum, J (Dec 1983). "Thienamycin: development of imipenen-cilastatin.". The Journal of antimicrobial chemotherapy. 12 Suppl D: 1–35. doi:10.1093/jac/12.suppl_d.1. PMID 6365872.

[5] Kesado, Tadataka; Hashizume, Terutaka; Asahi, Yoshinari (1980). "Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics". Antimicrobial Agents and Chemotherapy. 17 (6): 912–7. doi:10.1128/aac.17.6.912. PMC 283902. PMID 6931548.

[6] "Imipenem spectrum of bacterial susceptibility and Resistance" (PDF). Retrieved 4 May 2012.

匿名

検索

案内

案内

imipenem