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antibiotic drug of the penicillin family used in the treatment of certain staphylococcal infections

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/13 17:44:35」(JST)

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Meticillin (INN, BAN) or methicillin (USAN, AAN) is a narrow-spectrum β-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline. In 2005, the name of the drug was changed from methicillin to meticillin in accordance with the International Pharmacopoeia guidelines.^[1]

Medical uses

Meticillin is no longer used to treat patients. Compared to other β-lactamase-resistant penicillins, it is less active, can be administered only parenterally, and has a higher frequency of interstitial nephritis, an otherwise-rare side effect of penicillins. However, selection of Meticillin depended on the outcome of susceptibility test of the microorganism, since it is no longer produced, it is also not routinely tested any more. It also served a purpose in the laboratory to determine the antibiotic sensitivity of Staphylococcus aureus to other β-lactamase-resistant penicillins; this role has now been passed on to other penicillines, namely Cloxacillin as well as genetic testing for the presence of mecA gene by PCR.

Spectrum of activity

At one time, meticillin was used to treat infections caused by certain Gram-positive bacteria including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, and Streptococcus pneumoniae. Today, meticillin is not as effective against these organisms due to resistance.

Resistance to meticillin is conferred by activation of a new bacterial PBP gene (mecA). This encodes protein PBP2a. PBP2a works in a similar manner to other PBPs, but it binds β-lactams with very low affinity, meaning they do not compete efficiently with the natural substrate of the enzyme and will not inhibit cell wall biosynthesis. Expression of PBPA2 confers resistance to all β-lactams.

These susceptibility data are given on a few medically significant bacteria:

Staphylococcus aureus - 0.125 - >100 μg/ml
Meticillin resistant Staphylococcus aureus (MRSA) - 15.6 - >1000 μg/ml
Streptococcus pneumoniae 0.39 μg/ml

^[2]

Mechanism of action

Like other beta-lactam antibiotics, meticillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. It does this by binding to and competitively inhibiting the transpeptidase enzyme (also known as penicillin-binding proteins (PBPs)). These PBPs crosslink glycopeptides (D-alanyl-alanine), forming the peptidoglycan cell wall. Meticillin and other β-lactam antibiotics are structural analogs of D-alanyl-alanine, and the transpeptidase enzymes that bind to them are sometimes called penicillin-binding proteins (PBPs).^[3]

Meticillin is actually a penicillinase-resistant B-lactam antibiotic. Penicillinase is a bacterial enzyme produced by bacteria resistant to other B-lactam antibiotics which hydrolyses the antibiotic, rendering it nonfunctional. Meticillin is not bound and hydrolysed by penicillinase, meaning it can kill the bacteria, even if this enzyme is present.

Medicinal chemistry

Meticillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the ortho-dimethoxyphenyl group directly attached to the side-chain carbonyl group of the penicillin nucleus facilitates the β-lactamase resistance, since those enzymes are relatively intolerant of side-chain steric hindrance. Thus, it is able to bind to PBPs and inhibit peptidoglycan crosslinking, but it is not bound by or inactivated by β-lactamases.

History

Meticillin was developed by Beecham in 1959.^[4] It was previously used to treat infections caused by susceptible Gram-positive bacteria, in particular, penicillinase-producing organisms such as Staphylococcus aureus that would otherwise be resistant to most penicillins.

Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, but the term meticillin-resistant Staphylococcus aureus (MRSA) continues to be used to describe S. aureus strains resistant to all penicillins.^[5]

Meticillin is no longer manufactured because the more stable and similar penicillins such as oxacillin (used for clinical antimicrobial susceptibility testing), flucloxacillin, and dicloxacillin are used medically.

References

^ UK parliament MRSA
^ http://www.toku-e.com/Assets/MIC/Methicillin%20sodium.pdf
^ Gladwin M., Trattler B. Clinical Microbiology made ridiculously simple. 3rd edition. Miami: MedMaster, Inc.; 2004.
^ Graham Dutfield (30 July 2009). Intellectual property rights and the life science industries: past, present and future. World Scientific. pp. 140–. ISBN 978-981-283-227-6. Retrieved 18 November 2010.
^ MRSA—past, present, future

UpToDate Contents

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1. メチシリン耐性黄色ブドウ球菌の微生物学 microbiology of methicillin resistant staphylococcus aureus
2. 成人におけるメチシリン耐性黄色ブドウ球菌感染症：疫学 methicillin resistant staphylococcus aureus infection in adults epidemiology
3. 成人における侵襲性メチシリン耐性黄色ブドウ球菌感染症の治療 treatment of invasive methicillin resistant staphylococcus aureus infections in adults
4. 成人におけるメチシリン耐性黄色ブドウ球菌：予防および管理 methicillin resistant staphylococcus aureus in adults prevention and control
5. 成人におけるメチシリン耐性黄色ブドウ球菌による皮膚および軟部組織感染症の治療 treatment of skin and soft tissue infections due to methicillin resistant staphylococcus aureus in adults

English Journal

Detection of methicillin-resistant staphylococci by biosensor assay consisting of nanoscale films on optical fiber long-period gratings.

Bandara AB1, Zuo Z2, Ramachandran S3, Ritter A4, Heflin JR5, Inzana TJ6.
Biosensors & bioelectronics.Biosens Bioelectron.2015 Aug 15;70:433-40. doi: 10.1016/j.bios.2015.03.041. Epub 2015 Mar 30.
Methicillin-resistance among Staphylococcus species is a major health problem in hospitals, communities, and animals. There is a need for culture-free diagnostic assays that can be carried out rapidly, and maintain a high degree of sensitivity and specificity. To address this need an ionic self-asse
PMID 25845336

An off-the-shelf plasma-based material to prevent pacemaker pocket infection.

Schwartzman D1, Pasculle AW2, Ceceris KD3, Smith JD3, Weiss LE4, Campbell PG5.
Biomaterials.Biomaterials.2015 Aug;60:1-8. doi: 10.1016/j.biomaterials.2015.04.042. Epub 2015 May 14.
Bacterial infection of subcutaneous "pockets" housing cardiovascular implantable electronic devices is a significant clinical complication. In this study, pacemakers encapsulated in a blood plasma-based material (PBM) composited with antibiotics were investigated for use as prophylactics against suc
PMID 25965281

Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors.

Pardeshi KA1, Malwal SR1, Banerjee A2, Lahiri S2, Rangarajan R2, Chakrapani H3.
Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2015 Jul 1;25(13):2694-7. doi: 10.1016/j.bmcl.2015.04.046. Epub 2015 Apr 23.
Drug resistant infections are becoming common worldwide and new strategies for drug development are necessary. Here, we report the synthesis and evaluation of 2,4-dinitrophenylsulfonamides, which are donors of sulfur dioxide (SO2), a reactive sulfur species, as methicillin-resistant Staphylococcus a
PMID 25981687

Japanese Journal

Distribution of Major Staphylococcal Cassette Chromosome mec Types and Exfoliative Toxin Genes in Staphylococcus pseudintermedius Strains from Dogs with Superficial Pyoderma in Japan

麻布大学雑誌 = Journal of Azabu University 27, 27-31, 2016-03-31
NAID 120005732080

臨床経験 MRSA/MRCNS骨関節炎に対するリネゾリドとダプトマイシンの治療経験

臨床整形外科 51(1), 81-85, 2016-01
NAID 40020712322

メシチリン耐性黄色ブドウ球菌 (今月の特集グローバル化時代の耐性菌感染症)

臨床検査 60(1), 52-60, 2016-01
NAID 40020692811

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★リンクテーブル★

リンク元	「薬理学」「メチシリン」「meticillin sodium」「meticillin」
拡張検索	「methicillin-sensitive Staphylococcus aureus」「methicillin resistant Staphylococcus aureus」「methicillin-susceptible Staphylococcus aureus」「methicillin resistant S. aureus」「methicillin-resistant Staphylococcms aureus」

「薬理学」

Meticillin
Systematic (IUPAC) name
	(2S,5R,6R)-6-(2,6-dimethoxybenzamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Clinical data
Routes of; administration	IV
Pharmacokinetic data
Bioavailability	Not orally absorbed
Metabolism	hepatic, 20–40%
Biological half-life	25–60 minutes
Excretion	renal
Identifiers
CAS Number	61-32-5
ATC code	J01CF03 (WHO) QJ51CF03 (WHO)
PubChem	CID 6087
DrugBank	DB01603
ChemSpider	5862
UNII	Q91FH1328A
ChEMBL	CHEMBL575
Chemical data
Formula	C17H20N2O6S
Molar mass	380.42 g/mol
	SMILES OC(=O)[C@@H]2N3C(=O)[C@@H](NC(=O)c1c(OC)cccc1OC)[C@H]3SC2(C)C ;
(what is this?) (verify)

　　[★]

英: pharmacology
関: drug entries

定義

生物系と化学物質の選択的な相互作用を研究する学問 (SPC.2)

生物系と薬の相互作用

薬の生物系に対する相互作用：薬理作用 <-化学の視点
生物系の薬に対する相互作用：薬物動態 <-生物の視点

薬品の命名

Ending of the drug name	Category	Example
～afil	Erectile dysfunction	sildenafil
～ane	Inhalatinal general anesthetic	halothane
～azepam	Benzodiaizepine	diazepam
～azine	Phenothiazine (neuroleptic, antiemetic)	chlorpromazine
～azole	Ailtifungal	ketoconazole
～barbital	Barbiturate	phenobarbital
～caine	Local anesthetic	lidocaine
～cillin	Penicillin	methicillin
～cycline	Antibiotic, protein syntlesis inhibitor	tetracycline
～ipramine	TCA	iimipramine
～navir	Protease inhibitor	saquinavir
～olol	β-antagonist	propranolol
～operidol	Butyrophenone ( neuroleptic )	haloperidol
～oxin	Cardiac glycoside ( inotropic agent )	digoxin
～phylline	Methylxanthine	theophylline
～pril	ACE inhibitor	captopril
～terol	β₂ agonist	albuterol
～tidine	H₂ antagonist	cimtidine
～triptyline	TCA	amitriptyline
～tropine	Pituitary hormone	somatotropine
～zosin	a₁ antagonist	prazosin

薬一覧

薬物代謝

薬理動態

神経伝達物質

貧血治療薬

甲状腺関連物質

甲状腺ホルモン製剤

レボチロキシン levothyroxine
リオチニシン liothyronine

抗甲状腺薬

痛風治療薬

痛風発作予防薬

コルヒチン colchicine

尿酸排泄促進薬

尿酸生成抑制薬

アロプリノール allopurinol

「メチシリン」

　　[★]

英: methicillin
同: ジメトキシフェニルペニシリン dimethoxyphenylpenicillin DMPPC
関

「meticillin sodium」

　　[★]

メチシリンナトリウム

関: methicillin、meticillin

「meticillin」

　　[★]

メチシリン

関: methicillin、meticillin sodium

「methicillin-sensitive Staphylococcus aureus」

　　[★] メチシリン感受性黄色ブドウ球菌 MSSA

「methicillin resistant Staphylococcus aureus」

　　[★] メチシリン耐性黄色ブドウ球菌 MRSA

「methicillin-susceptible Staphylococcus aureus」

　　[★] メチシリン感受性黄色ブドウ球菌

「methicillin resistant S. aureus」

　　[★] メチシリン耐性黄色ブドウ球菌

「methicillin-resistant Staphylococcms aureus」