Meticillin

Meticillin

Systematic (IUPAC) name
(2S,5R,6R)-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Clinical data
Pregnancy cat.	?
Legal status	?
Routes	IV
Pharmacokinetic data
Bioavailability	Not orally absorbed
Metabolism	hepatic, 20–40%
Half-life	25–60 minutes
Excretion	renal
Identifiers
CAS number	61-32-5 Y
ATC code	J01CF03 QJ51CF03
PubChem	CID 6087
DrugBank	DB01603
ChemSpider	5862 N
UNII	Q91FH1328A N
ChEMBL	CHEMBL575 N
Chemical data
Formula	C17H20N2O6S
Mol. mass	380.42 g/mol
SMILES	eMolecules & PubChem
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Meticillin (INN, BAN) or methicillin (USAN) is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline.

History

Methicillin was developed by Beecham in 1959.^[1] It was previously used to treat infections caused by susceptible Gram-positive bacteria, in particular, beta-lactamase-producing organisms such as Staphylococcus aureus that would otherwise be resistant to most penicillins, but it is no longer clinically used.

Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the term methicillin-resistant Staphylococcus aureus (MRSA) continues to be used to describe Staphylococcus aureus strains resistant to all penicillins.

Methicillin 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.

Mode of action

Main article: Beta-lactam antibiotic

Like other beta-lactam antibiotics, methicillin 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 used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidoglycan synthesis. Methicillin and other beta-lactam antibiotics are structural analogs of D-alanyl-alanine, and the transpeptidase enzymes that bind to them are sometimes called penicillin-binding proteins (PBPs). ^[2]

Medicinal chemistry

Methicillin 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 penicillin-binding proteins (PBPs) and inhibit peptidoglycan crosslinking, but it is not bound by or inactivated by β-lactamases.

Clinical use

Methicillin is no longer used to treat patients. Compared to other beta-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. But it serves a purpose in the laboratory to determine the antibiotic sensitivity of Staphylococcus aureus to other beta-lactamase-resistant penicillins.

References

1. ^ Graham Dutfield (30 July 2009). Intellectual property rights and the life science industries: past, present and future. World Scientific. pp. 140–. ISBN 9789812832276. http://books.google.com/books?id=hnleY38aUxYC&pg=PA140. Retrieved 18 November 2010. 
2. ^ Gladwin M., Trattler B. Clinical Microbiology made ridiculously simple. 3rd edition. Miami: MedMaster, Inc.; 2004.