flucloxacillin

Flucloxacillin is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone.

Flucloxacillin is used for both staphylococcal and streptococcal skin infections.Stanway, Amy. {{cite web|url=http://www.dermnetnz.org/topics/streptococcal-skin-infections/|title=Streptococcal skin infection – DermNet New Zealand|website=www.dermnetnz.org|date=26 October 2023 }} These include folliculitis, carbuncles,{{Cite book| vauthors = Gould K | chapter-url=https://books.google.com/books?id=uM6SDAAAQBAJ&pg=PA177|title=Oxford Textbook of Fundamentals of Surgery |date=2016|publisher=Oxford University Press|isbn=978-0-19-966554-9| veditors = Thomas WE, Reed MW, Wyatt MG |pages=176–177|language=en|chapter=1.6 Applied surgical microbiology}} impetigo, ecthyma, cellulitis, erysipelas, necrotising fasciitis, and infections of skin conditions such as eczema, scabies, ulcers and acne.{{cite web |title=Flucloxacillin 125mg/5ml Oral solution – Summary of Product Characteristics (SmPC) – (emc) |url=https://www.medicines.org.uk/emc/product/527/smpc |website=medicines.org.uk |access-date=16 December 2020 |archive-date=2 March 2021 |archive-url=https://web.archive.org/web/20210302053327/https://www.medicines.org.uk/emc/product/527/smpc |url-status=dead }} Due to the widespread belief that dual-therapy is needed to cover both Staphylococcus and Streptococcus in cellulitis, flucloxacillin is sometimes given with the addition of benzylpenicillin for more severe cellulitis. However, support for this practice has lessened since findings in a study published in the Emergency Medicine Journal in 2005 did not show this combination to give additional clinical benefit.{{cite journal | vauthors = Leman P, Mukherjee D | title = Flucloxacillin alone or combined with benzylpenicillin to treat lower limb cellulitis: a randomised controlled trial | journal = Emergency Medicine Journal | volume = 22 | issue = 5 | pages = 342–6 | date = May 2005 | pmid = 15843702 | pmc = 1726763 | doi = 10.1136/emj.2004.019869 }}{{Cite book| vauthors = Sarkar R, Nair V, Sinha S, Garg VK, Rodriguez DA |chapter-url=https://books.google.com/books?id=ERVywKMMqAsC&pg=PA121|title=Treatments for Skin of Color E-Book|date=2011|publisher=Saunders Elsevier|isbn=978-1-4377-0859-2| veditors = Taylor S, Gathers RC, Callender VD, Rodriguez DA, Badreshia-Bansal SC |pages=121|language=en|chapter=7. Infectious diseases}}{{Cite book| vauthors = Cox NH |chapter-url=https://books.google.com/books?id=SbsQij5xkfYC&q=Flucloxacillin+alone+or+combined+with+benzylpenicillin&pg=PA409|title=Evidence-Based Dermatology|date=2009|publisher=Blackwell Publishing|isbn=978-1-4051-4518-3| veditors = Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B |edition=2nd|pages=409|language=en|chapter=41. Streptococcal Cellulitis/Erysipelas of the lower leg}} In the UK, using flucloxacillin alone is the first choice for treating cellulitis. Some other countries vary.{{cite journal | vauthors = Sullivan T, de Barra E | title = Diagnosis and management of cellulitis | journal = Clinical Medicine | volume = 18 | issue = 2 | pages = 160–163 | date = March 2018 | pmid = 29626022 | pmc = 6303460 | doi = 10.7861/clinmedicine.18-2-160 }}

File:Impetigo2020.jpg|Impetigo

File:Facial erysipelas.jpg|Erysipelas

File:Folliculitis2.jpg|Folliculitis

File:Cellulitis1.jpg|Cellulitis

File:Carbuncle.jpg|Carbuncle

Infections of leg ulcers can be treated with flucloxacillin. With diabetic foot infections the dose is adjusted according to whether the infection appears mild, moderate or severe.

Despite having a lower than optimum drug penetration into bone ratio of 10–20%, flucloxacillin appears effective in treating osteomyelitis.{{cite journal | vauthors = Preiss H, Kriechling P, Montrasio G, Huber T, Janssen İ, Moldovan A, Lipsky BA, Uçkay İ | title = Oral Flucloxacillin for Treating Osteomyelitis: A Narrative Review of Clinical Practice | journal = Journal of Bone and Joint Infection | volume = 5 | issue = 1 | pages = 16–24 | date = 1 January 2020 | pmid = 32117685 | pmc = 7045523 | doi = 10.7150/jbji.40667 }}{{cite journal | vauthors = Thabit AK, Fatani DF, Bamakhrama MS, Barnawi OA, Basudan LO, Alhejaili SF | title = Antibiotic penetration into bone and joints: An updated review | language = en | journal = International Journal of Infectious Diseases | volume = 81 | pages = 128–136 | date = April 2019 | pmid = 30772469 | doi = 10.1016/j.ijid.2019.02.005 | doi-access = free }}

Depending on local guidance it may be used in the treatment of infection of joints while waiting for culture results.{{cite book| vauthors = Kumar P, Clark ML |title=Kumar & Clark's Medical Management and Therapeutics – E-Book|chapter-url=https://books.google.com/books?id=RUHFAAAAQBAJ&pg=PA322|year=2011|publisher=Elsevier|isbn=978-0-7020-2765-9|page=322|chapter=9. Drugs in Rheumatology}}

It may be used in combination with other antibiotics to treat pneumonia and can be used to prevent infection before surgery, particularly heart, lung, or bone surgery. When used to treat endocarditis, in combination with other antibiotics or alone, the dose of flucloxacillin may need to exceed the usual dose.

Despite flucloxacillin being insensitive to beta-lactamases, some organisms have developed resistance to it and other narrow-spectrum β-lactam antibiotics including methicillin. Such organisms include methicillin-resistant Staphylococcus aureus, which has developed resistance to flucloxacillin and other penicillins by having an altered penicillin-binding protein.{{cite journal | vauthors = Harvey K, Pavillard R | title = Methicillin resistance in Staphylococcus aureus with particular reference to Victorian strains | journal = The Medical Journal of Australia | volume = 1 | issue = 11 | pages = 465–467 | date = May 1982 | pmid = 7048040 | doi = 10.5694/j.1326-5377.1982.tb132417.x | s2cid = 204066905 }}

Common side effects 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.

Rarely, in fewer than 1 in 1,000 people, cholestatic jaundice (also referred to as cholestatic hepatitis) has been associated with flucloxacillin therapy. It may appear as pale stool with dark urine, and yellowish eyes and skin. The reaction may occur up to several weeks after treatment has stopped, and takes weeks to resolve. The estimated incidence is one in 15,000 exposures, and is more frequent in people over the age of 55, females, and those with a treatment duration of longer than two weeks.

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 administered to those with a history of cholestatic hepatitis associated with the use of dicloxacillin or flucloxacillin.

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.

It should be taken on an empty stomach, one half to one hour before food, as absorption is reduced when taken with food,{{cite web |title=New Zealand Consumer Medicine Information |url=http://www.medsafe.govt.nz/Consumers/CMI/f/flucloxacillin-aft.pdf |work=medsafe.govt.nz}} though some studies suggest that this does not compromise flucloxacillin plasma concentrations in most circumstances.{{cite journal | vauthors = Gardiner SJ, Drennan PG, Begg R, Zhang M, Green JK, Isenman HL, Everts RJ, Chambers ST, Begg EJ | title = In healthy volunteers, taking flucloxacillin with food does not compromise effective plasma concentrations in most circumstances | journal = PLOS ONE | volume = 13 | issue = 7 | pages = e0199370 | year = 2018 | pmid = 30001392 | pmc = 6042703 | doi = 10.1371/journal.pone.0199370 | bibcode = 2018PLoSO..1399370G | doi-access = free }}

The UK's National Health Service recommends taking at least 30 minutes before food and at least 2 hours after.{{Cite web|url=https://www.nhs.uk/medicines/flucloxacillin/|title=Flucloxacillin: antibiotic to treat infections|date=27 November 2018|website=nhs.uk}}

Flucloxacillin can reduce the excretion of methotrexate, potentially resulting in a risk of methotrexate toxicity. The level of flucloxacillin in the blood may rise in kidney failure and with the use of probenecid.

{{main article|Beta-lactam antibiotic}}

Flucloxacillin is a narrow-spectrum antibiotic belonging to the penicillin group of antibiotics.{{cite web |title=Flucloxacillin sodium salt|url=https://pubchem.ncbi.nlm.nih.gov/compound/Flucloxacillin-sodium-salt|access-date=13 December 2020|website=pubchem.ncbi.nlm.nih.gov|publisher=PubChem at the National Institutes of Health|language=en}} It works by breaking down the bacterial cell wall.

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.{{fact|date=November 2021}}

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.{{fact|date=November 2021}}

Flucloxacillin has similar pharmacokinetics, antibacterial activity, and indications to dicloxacillin, and the two agents are considered interchangeable. It is reported to have higher, though rare, incidence of severe hepatic adverse effects than dicloxacillin,{{cite book |title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |date=2012 |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK548106/ |chapter=Dicloxacillin |pmid=31643436 }} but a lower incidence of renal adverse effects.Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.

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 and inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.{{fact|date=November 2021}}

Flucloxacillin was developed in the 1960s following an increase in penicillin-resistant (beta-lactamase producing) staphylococcal infections due to the widespread use of benzylpenicillin by 1960.{{cite book | vauthors = White RJ | veditors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery II |date=2010 |publisher=Wiley-VCH |isbn=978-1-4614-1399-8 |page=11 |url=https://books.google.com/books?id=h2Kd8ci4Ln8C |language=en}}{{cite book |doi=10.1007/978-1-4614-1400-1_3 |chapter=Beta-Lactam Antibiotics |title=Antibiotic Discovery and Development |year=2012 | vauthors = Page MG |pages=79–117 |isbn=978-1-4614-1399-8 }} All the natural penicillins and first semi-synthetic penicillins were destroyed by staphylococcal beta-lactamase, leading Beecham (later GlaxoSmithKline) to search for more stable antibiotics. By 1962, a series of similarly structured acid-stable penicillins (oxacillin, cloxacillin, dicloxacillin and flucloxacillin), with the potential for being taken by mouth, were developed. Flucloxacillin and dicloxacillin showed particular stability against the beta-lactamase enzyme of Staph. aureus and could withstand acid. Beecham further developed cloxacillin and popularised flucloxacillin in the UK, while Bristol Laboratories concentrated on marketing oxacillin and dicloxacillin in the United States, leading to the difference in use in both countries.{{cite book| vauthors = Greenwood D |title=Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph|chapter-url=https://books.google.com/books?id=i4_FZHmzjzwC&pg=PA124|year=2008|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-953484-5|page=124|chapter=4. Wonder Drugs}}{{cite journal | vauthors = Sutherland R, Croydon EA, Rolinson GN | title = Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin | journal = British Medical Journal | volume = 4 | issue = 5733 | pages = 455–60 | date = November 1970 | pmid = 5481218 | pmc = 1820086 | doi = 10.1136/bmj.4.5733.455 }} Flucloxacillin was first marketed in Europe in the 1970s.

Both the oral and intravenous preparations of flucloxacillin are inexpensive and are 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, 1000 and 2000 mg per vial).{{cite web |title=Search Results – Flucloxacillin |url=https://www.medicines.org.uk/emc/search?q=flucloxacillin |website=medicines.org.uk |access-date=16 December 2020}}

Flucloxacillin is not commonly used in the United States or Canada as of 2011, but is the most commonly prescribed narrow-spectrum penicillinase-resistant penicillin in the UK.{{cite journal | vauthors = Francis NA, Hood K, Lyons R, Butler CC | title = Understanding flucloxacillin prescribing trends and treatment non-response in UK primary care: a Clinical Practice Research Datalink (CPRD) study | journal = The Journal of Antimicrobial Chemotherapy | volume = 71 | issue = 7 | pages = 2037–2046 | date = July 2016 | pmid = 27090629 | pmc = 4896409 | doi = 10.1093/jac/dkw084 }} It is supplied under a variety of trade names including Floxapen, Flopen, Flubex, Flupen, Phylopen, and Staphylex.

{{main article|Co-fluampicil}}

Flucloxacillin is combined with ampicillin in co-fluampicil.

File:Flucloxacillin powder for oral solution.jpg|Flucloxacillin powder for oral solution 125 mg/5ml, with measuring spoon

File:Flucloxacillin preparations.jpg|Selection of Flucloxacillin preparations found in the UK

File:Co-fluampicil capsules and container.jpg|Co-fluampicil: Flucloxacillin combined with ampicillin (UK)

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