methicillin

Absorption

Not absorbed following oral administration.

Description

Methicillin is a member of the penicillin family of antibiotics. Its synthesis from 6-aminopnicillanic acid was patented by F. P. Doyle and co-inventors in 1960. Methicillin is a narrow-spectrum drug that has been replaced by more stable and efficacious penicillin derivatives. Now it is best known as the M in MRSA (methicillin-resistant?Staphylococcus aureus), a term for?S. Aureus?strains that resist all penicillins. In 2005, the International Pharmacopoeia guidelines changed the name of the drug to meticillin, but the original name is still widely used in the United States.

The Uses of methicillin

Antibacterial.

Indications

Used to treat infections caused by susceptible Gram-positive bacteria, particularly beta-lactamase-producing organisms such as Staphylococcus aureus that would otherwise be resistant to most penicillins.

Background

One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection.

Definition

ChEBI: A penicillin that is 6-aminopenicillanic acid in which one of the amino hydrogens is replaced by a 2,6-dimethoxybenzoyl group.

brand name

Staphcillin (Apothecon).

Antimicrobial activity

2,6-Dimethoxyphenylpenicillin; methicillin (international non-proprietary name). The first β-lactamase-resistant semisynthetic penicillin. It was initially used widely but has been superseded by other group 3 members and is no longer commercially available.
It is less active than benzylpenicillin or other group 3 penicillins. It is very stable to staphylococcal β-lactamase and is active against β-lactamaseproducing strains of Staph. aureus that do not produce a functional PBP 2a. Resistance is common among staphylococci, with the incidence geographically diverse. Most methicillin-resistant staphylococcal isolates display multiresistance.
It is not acid resistant, and must therefore be administered parenterally. About 10% is metabolized, with 60–80% of the dose excreted in the urine. Toxicity is similar to that of other group 3 penicillins. Nephritis appears to be more common than with other penicillins.

Pharmacokinetics

Meticillin (INN, BAN) or methicillin (USAN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. 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.

Pharmacology

Like other semisynthetic penicillins, methicillin exhibits an antibacterial effect similar to that of benzylpenicillin. The main difference between methicillin and benzylpenicillin is that it is not inactivated by the enzyme penicillinase, and therefore it is effective with respect to agents producing this enzyme (staphylococci). It is used for infections caused by benzylpenicillinresistant staphylococci (septicemia, pneumonia, empyemia, osteomyelitis, abscesses, infected wounds, and others). Synonyms of this drug are cinopenil, celbenin, staphcillin, and others.

Synthesis

Methicillin, [2S-(2|á,5|á,6|?)]-3,3-dimethyl-7-oxo-6-(2,6-dimethoxybenzamido)- 4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.3), is synthesized by acylating 6- APA with 2,6-dimethoxybenzoic acid chloride in the presence of triethylamine.

Metabolism

Hepatic (20-40%).