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- amdinocillin
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/26 12:49:26」(JST)
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Amdinocillin
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| Systematic (IUPAC) name |
| (2S,5R,6R)-6-[(azepan-1-ylmethylene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid |
| Clinical data |
| AHFS/Drugs.com |
International Drug Names |
| Pregnancy cat. |
B (US)
Appears safe in pregnancy[1] |
| Legal status |
℞ Prescription only |
| Routes |
Intravenous, intramuscular |
| Pharmacokinetic data |
| Bioavailability |
Negligible |
| Protein binding |
5 to 10% |
| Metabolism |
Some hepatic metabolism |
| Half-life |
1 to 3 hours |
| Excretion |
Renal and biliary, mostly unchanged |
| Identifiers |
| CAS number |
32887-01-7 Y |
| ATC code |
J01CA11 |
| PubChem |
CID 36273 |
| DrugBank |
DB01163 |
| ChemSpider |
33357 N |
| UNII |
V10579P3QZ N |
| KEGG |
D02888 N |
| ChEMBL |
CHEMBL530 Y |
| Chemical data |
| Formula |
C15H23N3O3S |
| Mol. mass |
325.426 g/mol |
SMILES
- CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)N=CN3CCCCCC3)C(=O)O)C
|
N (what is this?) (verify)
|
Mecillinam (INN) or amdinocillin (USAN), trade name Coactin, is an extended-spectrum penicillin antibiotic that binds specifically to penicillin binding protein 2 (PBP2),[2] and is only considered to be active against Gram-negative bacteria. It is used primarily in the treatment of urinary tract infections, and has also been used to treat typhoid and paratyphoid fever.[3][4] Because mecillinam has very low oral bioavailability, an orally active prodrug was developed: pivmecillinam. Neither drug is available in the United States.[5]
Contents
- 1 History
- 2 Activity
- 3 Adverse effects
- 4 References
History[edit]
With the codename FL 1060, mecillinam was developed by the Danish pharmaceutical company Leo Pharmaceutical Products (now LEO Pharma). It was first described in the scientific literature in a 1972 paper.[6][7]
Activity[edit]
Mecillinam is active against most pathogenic Gram-negative bacteria, except Pseudomonas aeruginosa and some species of Proteus.[5] Several studies have also found it to be as effective as other antibiotics for treating Staphylococcus saprophyticus infection, even though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine.[1]
Worldwide resistance to mecillinam in bacteria causing urinary tract infection has remained very low since its introduction; a 2003 study conducted in 16 European countries and Canada found resistance to range from 1.2% (Escherichia coli) to 5.2% (Proteus mirabilis).[8] Another large study conducted in Europe and Brazil obtained similar results — 95.9% of E. coli strains, for instance, were sensitive to mecillinam.[9]
Adverse effects[edit]
See also: Beta-lactam antibiotic: Adverse effects
The adverse effect profile of mecillinam is similar to that of other penicillins.[2] The most common side effects of mecillinam use are rash and gastrointestinal upset, including nausea and vomiting.[1]
References[edit]
- ^ a b c Nicolle LE (August 2000). = long&pmid = 10969050 "Pivmecillinam in the treatment of urinary tract infections". J Antimicrob Chemother 46 (Suppl A): 35–39. doi:10.1093/jac/46.suppl_1.35. PMID 10969050.
- ^ a b Neu HC (1985). "Amdinocillin: a novel penicillin. Antibacterial activity, pharmacology and clinical use". Pharmacotherapy 5 (1): 1–10. PMID 3885172.
- ^ Clarke PD, Geddes AM, McGhie D, Wall JC (July 1976). "Mecillinam: a new antibiotic for enteric fever". Br Med J 2 (6026): 14–5. doi:10.1136/bmj.2.6026.14. PMC 1687648. PMID 820402.
- ^ Geddes AM, Clarke PD (July 1977). "The treatment of enteric fever with mecillinam". J Antimicrob Chemother. 3 Suppl B: 101–2. PMID 408321.
- ^ a b Pham P, Bartlett JG (August 28, 2008). "Amdinocillin (Mecillinam)". Point-of-Care Information Technology ABX Guide. Johns Hopkins University. Retrieved on August 31, 2008. Freely available with registration.
- ^ Lund F, Tybring L (April 1972). "6β-amidinopenicillanic acids—a new group of antibiotics". Nature New Biol 236 (66): 135–7. doi:10.1038/236135c0. PMID 4402006.
- ^ Tybring L, Melchior NH (September 1975). "Mecillinam (FL 1060), a 6β-Amidinopenicillanic Acid Derivative: Bactericidal Action and Synergy In Vitro". Antimicrob Agents Chemother 8 (3): 271–6. PMC 429305. PMID 170856.
- ^ Kahlmeter G (January 2003). "An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO·SENS Project". J Antimicrob Chemother 51 (1): 69–76. doi:10.1093/jac/dkg028. PMID 12493789.
- ^ Naber KG, Schito G, Botto H, Palou J, Mazzei T (May 2008). "Surveillance Study in Europe and Brazil on Clinical Aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): Implications for Empiric Therapy". Eur Urol 54 (5): 1164–75. doi:10.1016/j.eururo.2008.05.010. PMID 18511178.
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Antibacterials: cell envelope antibiotics (J01C-J01D)
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|
| Intracellular |
- inhibit peptidoglycan subunit synthesis and transport: NAM synthesis inhibition (Fosfomycin)
- DADAL/AR inhibitors (Cycloserine)
- bactoprenol inhibitors (Bacitracin)
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| Glycopeptide |
- inhibit PG chain elongation: Vancomycin# (Oritavancin
- Telavancin)
- Teicoplanin (Dalbavancin)
- Ramoplanin
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β-lactams/
(inhibit PBP
cross-links) |
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Penicillins
(penams)
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Extended sp.
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- aminopenicillins: Amoxicillin#
- Ampicillin# (Pivampicillin
- Hetacillin
- Bacampicillin
- Metampicillin
- Talampicillin)
- Epicillin
- carboxypenicillins: Carbenicillin (Carindacillin)
- Ticarcillin
- Temocillin
- ureidopenicillins: Azlocillin
- Piperacillin
- Mezlocillin
- other: Mecillinam (Pivmecillinam)
- Sulbenicillin
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|
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Narrow sp.
|
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β-lactamase sensitive
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- Benzylpenicillin (G)#: Clometocillin
- Benzathine benzylpenicillin#
- Procaine benzylpenicillin#
- Azidocillin
- Penamecillin
- Phenoxymethylpenicillin (V)#: Propicillin
- Benzathine phenoxymethylpenicillin
- Pheneticillin
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|
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β-lactamase resistant
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- Cloxacillin# (Dicloxacillin
- Flucloxacillin)
- Oxacillin
- Meticillin
- Nafcillin
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|
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Penems
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Carbapenems
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- Biapenem
- Ertapenem
- antipseudomonal (Doripenem
- Imipenem
- Meropenem)
- Panipenem
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Cephalosporins/Cephamycins
(cephems)
|
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1st (PEcK)
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- Cefazolin#
- Cefacetrile
- Cefadroxil
- Cefalexin
- Cefaloglycin
- Cefalonium
- Cefaloridine
- Cefalotin
- Cefapirin
- Cefatrizine
- Cefazedone
- Cefazaflur
- Cefradine
- Cefroxadine
- Ceftezole
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2nd (HEN)
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- Cefaclor
- Cefamandole
- Cefminox
- Cefonicid
- Ceforanide
- Cefotiam
- Cefprozil
- Cefbuperazone
- Cefuroxime
- Cefuzonam
- cephamycin (Cefoxitin
- Cefotetan
- Cefmetazole)
- carbacephem (Loracarbef)
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3rd
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- Cefixime#
- Ceftriaxone#
- antipseudomonal (Ceftazidime#
- Cefoperazone)
- Cefcapene
- Cefdaloxime
- Cefdinir
- Cefditoren
- Cefetamet
- Cefmenoxime
- Cefodizime
- Cefotaxime
- Cefpimizole
- Cefpiramide
- Cefpodoxime
- Cefsulodin
- Cefteram
- Ceftibuten
- Ceftiolene
- Ceftizoxime
- oxacephem (Flomoxef
- Latamoxef ‡)
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4th (antips-)
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- Cefepime
- Cefozopran
- Cefpirome
- Cefquinome
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5th
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- Ceftobiprole
- Ceftaroline fosamil
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Veterinary
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- Ceftiofur
- Cefquinome
- Cefovecin
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Monobactams
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- Aztreonam
- Tigemonam
- Carumonam
- Nocardicin A
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|
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β-lactamase inh.
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- penam (Sulbactam
- Tazobactam)
- clavam (Clavulanic acid)
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Combinations
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- Amoxicillin/clavulanic acid#
- Imipenem/cilastatin#
- Ampicillin/flucloxacillin
- Ampicillin/sulbactam (Sultamicillin)
- Piperacillin/tazobactam
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|
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| Other |
- polymyxins/detergent (Colistin
- Polymyxin B)
- depolarizing (Daptomycin)
- hydrolyze NAM-NAG (Lysozyme)
- Gramicidin
- Isoniazid
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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gr+f/gr+a (t)/gr-p (c)/gr-o
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drug (J1p, w, n, m, vacc)
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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
- Indirect resistance to several classes of antibiotics in cocultures with resistant bacteria expressing antibiotic-modifying or -degrading enzymes.
- Nicoloff H1, Andersson DI2.
- The Journal of antimicrobial chemotherapy.J Antimicrob Chemother.2016 Jan;71(1):100-10. doi: 10.1093/jac/dkv312. Epub 2015 Oct 14.
- OBJECTIVES: Indirect resistance (IR), the ability of an antibiotic-resistant population of bacteria to protect a susceptible population, has been previously observed for β-lactamase-producing bacteria and associated with antimicrobial treatment failures. Here, we determined whether other resistance
- PMID 26467993
- Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase production.
- Mutters NT1, Zimmermann S1, Kaase M2, Mischnik A3,4.
- European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology.Eur J Clin Microbiol Infect Dis.2015 Dec;34(12):2429-37. doi: 10.1007/s10096-015-2498-3. Epub 2015 Oct 3.
- Treatment options for multidrug-resistant Gram-negative infections are scarce and therefore alternatives with a narrow spectrum or new agents are sought. Antimicrobial susceptibility to temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam was determined using Etest and disk diffusion accor
- PMID 26433746
Japanese Journal
- Novel S-Benzylisothiourea Compound That Induces Spherical Cells in Escherichia coli Probably by Acting on a Rod-shape-determining Protein(s) Other Than Penicillin-binding Protein 2(Microbiology & Fermentation Technology)
- Iwai Noritaka,Nagai Kazuo,Wachi Masaaki
- Bioscience, biotechnology, and biochemistry 66(12), 2658-2662, 2002-12-23
- … Mecillinam, a specific inhibitor of penicillin-binding protein 2, which induces spherical cells in E. … Spherical cells induced by treatment with either A22 or mecillinam varied in size, and anucleate cells seemed to be more frequent among the smaller cells. … No competition was observed even in the presence of a 10-fold excess A22 in an in vitro assay of ^<14>C-penicillin G binding, but mecillinam specifically inhibited binding of ^<14>C-penicillin G to penicillin-binding protein 2. …
- NAID 110002693615
- Studies on Prodrugs. VI. Preparation and Characterization of (5-Substituted 2-Oxo-1,3-dioxol-4-yl)methyl Esters of Mecillinam(Medicinal Chemistry,Chemical)
- 坂本 文夫,池田 昇司,平山 良一,森山 勝,外村 幹雄,塚本 悟郎
- Chemical & pharmaceutical bulletin 35(2), 642-646, 1987-02-25
- … As a new type of mecillinam prodrug, raecillinam (5-substituted 2-oxo-1,3-dioxol-4-yl)methyl esters were prepared. … These esters were found to produce at least 4-fold higher mecillinam levels in blood than mecillinam itself after oral administration to mice. … Mecillinam (5-methyl-2-oxo-1,3-dioxol-4-yl )methyl ester hydrochloride was hygroscopic, but its L-tartrate was not. …
- NAID 110006280947
- 金城 俊夫 [他],武藤 照美,木原 正子,源 宜之
- 岐阜大学農学部研究報告 51, 219-225, 1987-01-10
- エルシニアはY. pseudotuberculosisを除きβ-ラクタマーゼを産生する。このβ-ラクタマーゼ産生能に,エルシニアの菌種,生物型あるいは血清型によって,これらの分類の一助となりうるような差があるか否かを検討するため,各菌種のβ-ラクタム系抗生物質に対する感受性試験を行った。ヒト及び各種動物由来のY. enterocolitica B:1 81株,B:2 10株,B:3 30株,B:4 …
- NAID 110000976529
Related Links
- Mecillinam (INN) or amdinocillin (USAN), trade name Coactin, is an extended- spectrum penicillin antibiotic that binds specifically to penicillin binding protein 2 ( PBP2), and is only considered to be active against Gram-negative bacteria.
- Mecillinam: Rationale for the EUCAST clinical breakpoints, version 1.0. Page 1 of 10. Mecillinam. Rationale for the EUCAST clinical breakpoints, version 1.0. 22nd November 2010. Foreword. EUCAST. The European Committee on ...
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アムジノシリン
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- mecillinam
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- amdinocillin pivoxil、pivmecillinam
