OXACILLIN

Indications

In terms of the spectrum of antimicrobial action, oxacillin is analogous to benzylpenicillin. However, it combines the resistance to penicillinase with durability in an acidic medium, which allows it to be used not only intramuscularly, but also orally. It is used for infections caused by penicillinase-producing staphylococci that are resistant to benzyl- and phenoxymethylpenicillins (septicemia, pneumonia, abscesses, empyemia, osteomyelitis, infected burns, infected wounds, and others). Synonyms of this drug are cryptocillin, liucipen, optocillin, totocillin, and others.

Therapeutic Function

Antibacterial

Antimicrobial activity

There is complete cross-resistance and tolerance with other group 3 penicillins. Oxacillin is frequently used to replace methicillin for standardized susceptibility testing to detect resistant staphylococci.

Acquired resistance

In addition to methicillin-resistant strains producing the low affinity PBP 2a, rare methicillin-susceptible isolates of Staph. aureus display reduced susceptibility to oxacillin, due to incompletely defined chromosomal resistance mechanisms.

Contact allergens

Oxacillin is a semisynthetic penicillin of the group M. It is closely related to cloxacillin.

Side effects

There is cross-allergy with other penicillins and reactions are generally typical of the group. Abnormalities of liver function, especially elevation of transaminase levels, may occur, sometimes accompanied by fever, nausea, vomiting and eosinophilia. As with benzylpenicillin, neurotoxicity may develop on high dosage in patients with renal failure. Pseudomembranous colitis has been reported.

Synthesis

Oxacillin, [2S-(2α,5α,6β)]-3,3-dimethyl-7-oxo-6-(5-methyl-3-phenyl-4-isoxazolcarboxamido)-4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.10), is synthesized by reacting 5-methyl-3-phenyl-4-isoxazolcarboxylic acid chloride (32.1.1.9) with 6-APA in the presence of sodium bicarbonate. The 5-methyl-3-phenyl-4-isoxazolcarboxylic acid chloride (32.1.1.9) is synthesized by the following scheme. Reacting benzaldehyde with hydroxylamine gives benzaldoxime (32.1.1.5), which when oxidized by chlorine gives benzhydroxamic acid chloride (32.1.1.6). This is reacted with acetoacetic ester in the presence of sodium ethoxide, giving the ethyl ester of 5-methyl-3-phenyl-4-isoxazolcarboxylic acid (32.1.1.7). Alkaline hydrolysis of the resulting ester gives the corresponding acid (32.1.1.8), which is reacted with thionyl chloride to give the acid chloride necessary for acylation.

Definition

ChEBI: A penicillin antibiotic carrying a 5-methyl-3-phenylisoxazole-4-carboxamide group at position 6.