Oxacillin

Last updated
Oxacillin
Oxacillin skeletal.svg
Oxacillin-based-on-xtal-3D-bs-17.png
Clinical data
Trade names Bactocill
AHFS/Drugs.com Monograph
MedlinePlus a685020
ATC code
Identifiers
  • (2S,5R,6R)-3,3-dimethyl-6-[(5-methyl-3-phenyl-
    1,2-oxazole-4-carbonyl)amino]-7-oxo-4-thia-1-
    azabicyclo[3.2.0]heptane-2-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.577 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H19N3O5S
Molar mass 401.44 g·mol−1
3D model (JSmol)
Density 1.49 g/cm3
Boiling point 686.8 °C (1,268.2 °F)
  • [H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=CC=CC=C1)C(O)=O
  • InChI=1S/C19H19N3O5S/c1-9-11(12(21-27-9)10-7-5-4-6-8-10)15(23)20-13-16(24)22-14(18(25)26)19(2,3)28-17(13)22/h4-8,13-14,17H,1-3H3,(H,20,23)(H,25,26)/t13-,14+,17-/m1/s1 X mark.svgN
  • Key:UWYHMGVUTGAWSP-JKIFEVAISA-N X mark.svgN
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Oxacillin (trade name Bactocill) is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham. [1]

Contents

It was patented in 1960 and approved for medical use in 1962. [2]

Medical uses

Oxacillin is a penicillinase-resistant β-lactam. It is similar to methicillin, and has replaced methicillin in clinical use. Other related compounds are nafcillin, cloxacillin, dicloxacillin, and flucloxacillin. Since it is resistant to penicillinase enzymes, such as that produced by Staphylococcus aureus , it is widely used clinically in the US to treat penicillin-resistant Staphylococcus aureus . However, with the introduction and widespread use of both oxacillin and methicillin, antibiotic-resistant strains called methicillin-resistant and oxacillin-resistant Staphylococcus aureus (MRSA/ORSA) have become increasingly prevalent worldwide. MRSA/ORSA can be treated with vancomycin or other new antibiotics.[ citation needed ]

Contraindications

The use of oxacillin is contraindicated in individuals that have experienced a hypersensitivity reaction to any medication in the penicillin family of antibiotics. [3] Cross-allergenicity has been documented in individuals taking oxacillin that experienced a previous hypersensitivity reaction when given cephalosporins and cephamycins. [4] [5]

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. [3]

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. [6]

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. [6]

History

Oxacillin, a derivative of methicillin, was first synthesized in the early 1960s as part of a research initiative led by Peter Doyle and John Naylor of Beecham, in consort with Bristol-Myers. Members of the isoxazolyl penicillin family, which includes cloxacillin, dicloxacillin, and oxacillin, were synthesized to counter the increasing prevalence of infections caused by penicillin-resistant Staphylococcus aureus . 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. [1]

Society and Culture

FDA Approval History [3]

Pricing

The average wholesale price (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. [3]

Related Research Articles

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins 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 deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

<i>Staphylococcus aureus</i> Species of Gram-positive bacterium

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 for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

Methicillin-resistant <i>Staphylococcus aureus</i> Bacterium responsible for difficult-to-treat infections in humans

Methicillin-resistant Staphylococcus aureus (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths attributable to antimicrobial resistance in 2019.

<span class="mw-page-title-main">Ertapenem</span> Antibiotic medication

Ertapenem, sold under the brand name Invanz, is a carbapenem antibiotic medication used for the treatment of infections of the abdomen, the lungs, the upper part of the female reproductive system, and the diabetic foot.

<span class="mw-page-title-main">Methicillin</span> Antibiotic medication

Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">Cloxacillin</span> Beta-lactam antibiotic

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 (MRSA). It can be used by mouth and by injection.

<span class="mw-page-title-main">Cefuroxime axetil</span> Chemical compound

Cefuroxime axetil, sold under the brand name Ceftin among others, is a second generation oral cephalosporin antibiotic.

<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

<span class="mw-page-title-main">Flucloxacillin</span> Penicillin

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 treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent Staphylococcus infections. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA). It is taken by mouth or given by injection into a vein or muscle.

<span class="mw-page-title-main">Dicloxacillin</span> Chemical compound

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. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

<span class="mw-page-title-main">Penicillin-binding proteins</span> Class of proteins

Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered. All β-lactam antibiotics bind to PBPs, which are essential for bacterial cell wall synthesis. PBPs are members of a subgroup of enzymes called transpeptidases. Specifically, PBPs are DD-transpeptidases.

Antistaphylococcal penicillins are a chemical compound. They are a class of Beta lactam antibiotics used to treat infections caused by bacteria.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

<span class="mw-page-title-main">Dalbavancin</span> Antibiotic used to treat MRSA

Dalbavancin, sold under the brand names Dalvance in the US and Xydalba in the EU among others, is a second-generation lipoglycopeptide antibiotic medication. It belongs to the same class as vancomycin, the most widely used and one of the treatments available to people infected with methicillin-resistant Staphylococcus aureus (MRSA).

mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.

<span class="mw-page-title-main">Delafloxacin</span> Chemical compound

Delafloxacin sold under the brand name Baxdela among others, is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections.

<span class="mw-page-title-main">Ceftaroline fosamil</span> Chemical compound

Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.

Cephalosporins are a broad class of bactericidal antibiotics that include the β-lactam ring and share a structural similarity and mechanism of action with other β-lactam antibiotics. The cephalosporins have the ability to kill bacteria by inhibiting essential steps in the bacterial cell wall synthesis which in the end results in osmotic lysis and death of the bacterial cell. Cephalosporins are widely used antibiotics because of their clinical efficiency and desirable safety profile.

References

  1. 1 2 Greenwood D (2008). Antimicrobial drugs: chronicle of a twentieth century medical triumph. Oxford University Press US. pp. 124–. ISBN   978-0-19-953484-5 . Retrieved 18 November 2010.
  2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 490. ISBN   9783527607495.
  3. 1 2 3 4 Drugs.com: Bactocill
  4. ↑ Apothecon. Oxacillin sodium for injection for intramuscular or intravenous injection prescribing information. Princeton, NJ; 2001 Jan.
  5. ↑ Erffmeyer JE (October 1981). "Adverse reactions to penicillin. Part I". Annals of Allergy. 47 (4): 288–93. PMID   6171185.
  6. 1 2 Katzung B, Trevor A (2014). Basic and Clinical Pharmacology (13TH ed.). New York: Mcgraw-Hill. ISBN   978-0071825054 . Retrieved 3 November 2017.
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