Flucloxacillin
6-((S)-3-(2-chloro-6-fluorophenyl)-5-methylisoxazole- 4-carboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylic acid
CAS number 5250-39-5	ATC code J01CF05
PubChem CID 21319	DrugBank APRD00609
Chemical formula	C19H17CIFN3O5S
Molecular weight	453.87
Bioavailability	50–70%
Metabolism	hepatic
Elimination half-life	0.75–1 hour
Excretion	renal
Pregnancy category	B1 (Aust)
Legal status	Schedule 4 (Aust)
Routes of administration	oral, IM, IV, intrapleural, intraarticular

Flucloxacillin (INN) or floxacillin (USAN) is a narrow spectrum beta-lactam antibiotic. It is used to treat infections caused by susceptible Gram-positive bacteria. Notably, it is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. It is very similar to dicloxacillin and these two agents are considered interchangeable. Flucloxacillin is available under a variety of trade names including Flopen (CSL) and Floxapen (GSK). Image File history File links Flucloxacillin. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... PubChem is a database of chemical molecules . ... DrugBank is a database available at the University of Alberta that provides information about thousands of products. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos)) is the biochemical modification of chemical compounds in living organisms and cells. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... ‹ The template below has been proposed for deletion. ... The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... ‹ The template below has been proposed for deletion. ... Intramuscular injection is an injection of a substance directly into a muscle. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... The lungs are surrounded by two membranes, the pleurae. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... A United States Adopted Name (USAN) is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the United States Pharmacopeia (USP). ... A narrow-spectrum antibiotic is an antibiotic that is useful for a restricted group of microorganisms. ... β-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ... Subgroups Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular: bacterium) are a major group of living organisms. ... Beta-lactamase is a type of enzyme (EC 3. ... Binomial name Staphylococcus aureus Rosenbach, 1884 Staphylococcus aureus (which is occasionally given the nickname golden staph) is a bacterium, frequently living on the skin or in the nose of a healthy person, that can cause illnesses ranging from minor skin infections (such as pimples, boils, and cellulitis) and abscesses, to... Penicillin nucleus Penicillin refers to a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ... Dicloxacillin (INN) is a narrow spectrum beta-lactam antibiotic. ... CSL Limited is an Australian-based manufacturer of medical products. ... GlaxoSmithKline plc (LSE: GSK NYSE: GSK) is a British based pharmaceutical, biologicals, and healthcare company. ...

Mode of action

Main article: Beta-lactam antibiotic β-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure. ...

Like other β-lactam antibiotics, flucloxacillin 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. A cell wall is a more or less solid layer surrounding a cell. ... Peptidoglycan, also known as murein, is a substance that forms a homogeneous layer lying outside the plasma membrane in bacteria. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ...

Medicinal chemistry

Flucloxacillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the isoxazolyl group on the side chain of the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of side-chain steric hindrance. Thus it is able to bind to penicillin binding proteins (PBPs) and inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases. Beta-lactamase is a type of enzyme (EC 3. ... Steric effects are the interaction of molecules dictated by their shape and/or spatial relationships. ... Bacterial proteins that exhibit either transpeptidase or carboxypeptidase activity. ... Peptidoglycan, also known as murein, is a substance that forms a homogeneous layer lying outside the plasma membrane in bacteria. ...

Clinical use

Flucloxacillin is more acid-stable than many other penicillins and can be given orally, in addition to parenteral routes. However, like methicillin, it is less potent than benzylpenicillin against non-β-lactamase-producing Gram-positive bacteria. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Methicillin is an antibiotic related to penicillin and other beta-lactam containing antibiotics. ... Penicillin nucleus Penicillin refers to a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ...

Flucloxacillin has similar pharmacokinetics, antibacterial activity and indications to dicloxacillin and the two agents are considered interchangeable. It is believed to have higher incidence of severe hepatic adverse effects than dicloxacillin, but a lower incidence of renal adverse effects. (Rossi, 2006) Pharmacokinetics is a branch of pharmacology dedicated to the study of the time course of substances and their relationship with an organism or system. ... Adverse effect, in medicine, is an abnormal, harmful, undesired and/or unintended side-effect, although not necessarily unexpected, which is obtained as the result of a therapy or other medical intervention, such as drug/chemotherapy, physical therapy, surgery, medical procedure, use of a medical device, etc. ...

Available forms

Flucloxacillin is commercially available as the sodium salt flucloxacillin sodium, in capsules (250 or 500 mg), oral suspensions (125 mg/5 mL or 250 mg/5 mL), and injections (powder for reconstitution, 250, 500 and 1000 mg per vial). The word capsule (from the Latin capsula, a small box), has many similar meanings in English: In botany, a capsule is a type of dry fruit as in the poppy, iris, foxglove, etc. ... The milligram (symbol mg) is an SI unit of mass. ... Flour suspended in water In chemistry, a suspension is a colloidal dispersion (mixture) in which a finely-divided species is combined with another species, with the former being so finely divided and mixed that it doesnt rapidly settle out. ... The millilitre (spelled milliliter in American English and German) is a metric unit of volume that is equal to one thousandth of a litre. ...

Indications

Flucloxacillin is indicated for the treatment of infections caused by susceptible bacteria. Specific approved indications include: (Joint Formulary Committee, 2005; Rossi, 2006)

• Staphylococcal skin infections and cellulitis – including impetigo, otitis externa, folliculitis, boils, carbuncles, and mastitis
• Pneumonia (adjunct)
• Osteomyelitis, septic arthritis
• Septicaemia
• Empirical treatment for endocarditis
• Surgical prophylaxis

Flucloxacillin has relatively poor activity, as noted above, against non-β-lactamase-producing bacteria including Streptococcus pyogenes. Therefore empirical therapy for significant cellulitis often involves dual-therapy to cover both staphylococci and streptococci, using either penicillin or ampicillin in addition to flucloxacillin. The latter is available as a standardardised combination preparation co-fluampicil (flucloxacillin+ampicillin). Species S. aureus S. caprae S. epidermidis S. haemolyticus S. hominis S. lugdunensis S. saprophyticus S. warneri S. xylosus Staphylococcus (in Greek staphyle means bunch of grapes and coccos means granule) is a genus of gram-positive bacteria. ... Folliculitis is inflammation of one or more hair follicles. ... Boil or furuncle is a skin disease caused by the inflammation of hair follicles, thus resulting in the localized accumulation of pus and dead tissues. ... A carbuncle is an abscess larger than a boil, usually with one or more openings draining pus onto the skin. ... Mastitis is the inflammation of the mammalian breast caused by the blocking of the milk ducts while the mother is lactating (see breastfeeding). ... Pneumonia is an illness of the lungs and respiratory system in which the microscopic, air-filled sacs (alveoli) responsible for absorbing oxygen from the atmosphere become inflamed and flooded with fluid. ... Osteomyelitis is an infection of bone, usually caused by pyogenic bacteria or mycobacteria. ... Septic arthritis is the proliferation of bacteria in joints and resultant inflammation. ... Sepsis (in Greek Σήψις) is a serious medical condition caused by a severe systemic infection leading to a systemic inflammatory response. ... Empirical is an adjective often used in conjunction with science, both the natural and social sciences, which means an observation or experiment based upon experience that is capable of being verified or disproved. ... Endocarditis is an inflammation of the inner layer of the heart, the endocardium. ... Prophylaxis refers to any medical or public health procedure whose purpose is to prevent, rather than treat or cure, disease. ... The group A streptococcus bacterium (Streptococcus pyogenes) is responsible for most cases of streptococcal illness. ... Species S. aureus S. caprae S. epidermidis S. haemolyticus S. hominis S. lugdunensis S. saprophyticus S. warneri S. xylosus Staphylococcus (in Greek staphyle means bunch of grapes and coccos means granule) is a genus of gram-positive bacteria. ... Species S. agalactiae S. bovis S. pneumoniae S. pyogenes S. salivarius S. suis S. viridans Streptococcus is a genus of spherical, Gram-positive bacteria of the phylum Firmicutes. ... Penicillin nucleus Penicillin refers to a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ... Ampicillin (C16H18N3O4S) Ampicillin (C16H18N3O4S ; CAS No. ... Co-fluampicil is the British Approved Name, for the combination of ampicillin and flucloxacillin β-lactam antibiotics (trade name Magnapen®). // Indication Ampicillin is a moderate spectrum penicillin antibiotic with good cover against Group A streptococcal infection whilst Flucloxacillin is a narrow spectrum antibiotic with cover against Staphylococcus aureus. ...

Precautions/contraindications

Flucloxacillin is contraindicated in those with a previous history of allergy to penicillins, cephalosporins or carbapenems. It should also not be used in the eye, or those with a history of cholestatic hepatitis associated with the use of dicloxacillin or flucloxacillin. (Rossi, 2006) Penicillin nucleus Penicillin refers to a group of β-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ... The cephalosporins, are a class of β-lactam antibiotics. ... Carbapenems are a class of beta-lactam antibiotics. ... In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. ...

It should be used with caution in the elderly, patients with renal impairment, where a reduced dose is required; and those with hepatic impairment, due to the risk of cholestatic hepatitis. (Rossi, 2006)

Adverse effects

Common adverse drug reactions (ADRs) associated with the use of flucloxacillin include: diarrhoea, nausea, rash, urticaria, pain and inflammation at injection site, superinfection (including candidiasis), allergy, and transient increases in liver enzymes and bilirubin. (Rossi, 2006) An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... Diarrhoea is the correct way to spell the word Diarrhoea. ... For other uses, see Nausea (disambiguation). ... Red and Anarchist Skinheads is often referred to as RASH. A typical rash A rash is a change in the skin which affects its appearance or texture. ... Pain is an unpleasant sensation which may be associated with actual or potential tissue damage and which may have physical and emotional components. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... In virology, superinfection describes the process by which a cell that has previously been infected by one virus gets coinfected with another virus at a later point in time. ... An allergy or Type I hypersensitivity is an immune system malfunction whereby a persons body is hypersensitised to react immunologically to typically nonimmunogenic substances. ...

Rarely, cholestatic jaundice (also referred to as cholestatic hepatitis) has been associated with flucloxacillin therapy. The reaction may occur up to several weeks after treatment has stopped, and takes weeks to resolve. The estimated incidence is 1 in 15,000 exposures, and is more frequent in people >55 years, females, and those with treatment longer than 2 weeks. (Joint Formulary Committee, 2005; Rossi, 2006) In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. ...

Resistance

Despite flucloxacillin being insensitive to beta-lactamses, some organisms have developed resistance to it and other narrow-spectrum β-lactam antibiotics including methicillin. Such organisms include methicillin-resistant Staphylococcus aureus (MRSA). Electron micrograph of MRSA Methicillin-resistant Staphylococcus aureus, (MRSA) is a specific strain of the Staphylococcus aureus bacterium that has developed antibiotic resistance, first to penicillin since 1947, and later to methicillin and related anti-staphylococcal drugs. ...

See also

• Beta-lactam antibiotic
• Dicloxacillin

β-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure. ... Dicloxacillin (INN) is a narrow spectrum beta-lactam antibiotic. ...

References

• Joint Formulary Committee. British National Formulary, 50th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2005.
• Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.