Oxacillin (trade name Bactocill) is a narrow-spectrum

beta-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and ...

of the

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

class developed by

Beecham Beecham is a surname. Notable people with the surname include: * Audrey Beecham (1915–1989), poet and niece of the conductor * Betty Humby Beecham (1908–1958), British pianist and wife of the conductor * Earl Beecham (born 1965), American foo ...

. It was patented in 1960 and approved for medical use in 1962.

Medical uses

Oxacillin is a penicillinase-resistant

β-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the Β carbon, β-carbon atom relative to the carbonyl. The simplest β-lactam p ...

. It is similar to

methicillin Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class. Methicillin was discovered in 1960. Medical uses Compared to other penicillins that face antimicrobial resistance due ...

, and has replaced methicillin in clinical use. Other related compounds are

nafcillin Nafcillin sodium is a narrow-spectrum beta-lactam antibiotic of the penicillin class. As a beta-lactamase-resistant penicillin, it is used to treat infections caused by Gram-positive bacteria, in particular, species of staphylococci that are res ...

cloxacillin Cloxacillin is an antibiotic useful for the treatment of a number of bacterial infections. This includes impetigo, cellulitis, pneumonia, septic arthritis, and otitis externa. It is not effective for methicillin-resistant ''Staphylococcus aureus ...

dicloxacillin Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria.Product Information: DICLOXACILLIN SODIUM-dicloxacillin sodium capsule. T ...

, and

flucloxacillin Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to t ...

. Since it is resistant to penicillinase enzymes, such as that produced by ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...

'', it is widely used clinically in the US to treat penicillin-resistant ''

''. However, with the introduction and widespread use of both oxacillin and methicillin,

antibiotic-resistant Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...

strains called methicillin-resistant and oxacillin-resistant ''Staphylococcus aureus'' (MRSA/ORSA) have become increasingly prevalent worldwide. MRSA/ORSA can be treated with

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...

or other new antibiotics.

Contraindications

The use of oxacillin is contraindicated in individuals that have experienced a hypersensitivity reaction to any medication in the penicillin family of antibiotics.Drugs.com
Bactocill
/ref> Cross-allergenicity has been documented in individuals taking oxacillin that experienced a previous hypersensitivity reaction when given

cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...

and

cephamycins Cephamycins are a group of β-lactam antibiotics. They are very similar to cephalosporins, and the cephamycins are sometimes classified as cephalosporins. Like cephalosporins, cephamycins are based upon the cephem nucleus. Unlike most cephalospor ...

Adverse effects

Commonly reported adverse effects associated with the use of oxacillin include skin rash, diarrhea, nausea, vomiting, hematuria, agranulocytosis, eosinophilia, leukopenia, neutropenia, thrombocytopenia, hepatotoxicity, acute interstitial nephritis, and fever. High doses of oxacillin have been reported to cause renal, hepatic, and nervous system toxicity. Common to all members of the penicillin class of drugs, oxacillin may cause acute or delayed hypersensitivity reactions. As an injection, oxacillin may cause injection site reactions, which may be characterized by redness, swelling, and itching.

Pharmacology

Mechanism of Action

Oxacillin, through its β-lactam ring, covalently binds to penicillin-binding proteins, which are enzymes involved in the synthesis of the bacterial cell wall. This binding interaction interferes with the transpeptidation reaction and inhibits the synthesis of peptidoglycan, a prominent component of the cell wall. By decreasing the integrity of the bacterial cell wall, it is thought that oxacillin and other penicillins kill actively growing bacteria through cell autolysis.

Chemistry

As with other members of the penicillin family, the chemical structure of oxacillin features a 6-aminopenicillanic acid nucleus with a substituent attached to the amino group. The 6-aminopenicillanic acid nucleus consists of a thiazolidine ring attached to a β-lactam ring, which is the active moiety responsible for the antibacterial activity of the penicillin family. The substituent present on oxacillin is thought to impart resistance to degradation via bacterial β-lactamases.

History

Oxacillin, a derivative of

, was first synthesized in the early 1960s as part of a research initiative led by Peter Doyle and John Naylor of

, in consort with

Bristol-Myers The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...

. Members of the

isoxazolyl Isoxazole is an electron-rich azole with an oxygen atom next to the nitrogen. It is also the class of compounds containing this ring. Isoxazolyl is the univalent radical derived from isoxazole. Occurrence Isoxazole rings are found in some natural ...

penicillin family, which includes

, and oxacillin, were synthesized to counter the increasing prevalence of infections caused by penicillin-resistant ''

''. While methicillin could only be administered via injection, the isoxazolyl penicillins, including oxacillin, could be given orally or by injection. Following the synthesis of cloxacillin and oxacillin, Beecham retained the right to commercially develop cloxacillin in the United Kingdom while Bristol-Myers was given the marketing rights for oxacillin in the United States.

Society and Culture

FDA Approval History

*April 8, 1971: Oxacillin Sodium Injectable **Applicant: Sandoz *July 27, 1973: Bactocill Capsule **Applicant: GlaxoSmithKline *March 10, 1980: Oxacillin Sodium Capsule **Applicant: Ani Pharms Inc *May 15, 1980: Oxacillin Sodium for Solution **Applicant: TEVA *June 2, 1981: Bactocill for Solution **Applicant: GlaxoSmithKline *December 23, 1986: Oxacillin Sodium Powder **Applicant: Sandoz *September 29, 1988: Oxacillin Sodium Injectable **Applicant: Watson Labs Inc *October 26, 1988: Oxacillin Sodium Injectable **Applicant: Watson Labs Inc *October 26, 1989: Bactocill in Plastic Container Injectable **Applicant: Baxter Healthcare *March 30, 2012: Oxacillin Sodium Injectable **Applicant: Sagent Pharms *January 18, 2013: Oxacillin Sodium Injectable **Applicant: Aurobindo Pharma LTD *August 25, 2014: Oxacillin Sodium Injectable **Applicant: Mylan Labs LTD *December 11, 2015: Oxacillin Sodium Injectable **Applicant: Hospira Inc *July 31, 2017: Oxacillin Sodium Injectable **Applicant: Wockhardt Bio/Ag

Pricing

The

average wholesale price In the United States, the average wholesale price (AWP) is a prescription drug term referring to the average price for medications offered at the wholesale level. The metric was originally intended to convey real pricing information to third-party ...

(AWP) for oxacillin products are provided as follows. The prices listed below are intended to serve as reference values and do not represent the pricing determined by any single manufacturer or entity. *Bactocill in Dextrose Intravenous **1 g/50 mL: $20.37 **2 g/50 mL: $32.48 *Oxacillin Sodium Injection **1 g: $17.52 **2 g: $33.99 **10 g: $138.77

References

ChemBank
{{Cell wall disruptive antibiotics Penicillins Enantiopure drugs Isoxazoles