Flucloxacillin, also known as floxacillin, is an

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

used to treat

skin infections Skin and skin structure infections (SSSIs), also referred to as skin and soft tissue infections (SSTIs), or acute bacterial skin and skin structure infections (ABSSSIs), are infections of skin and associated soft tissues (such as loose connective ti ...

, 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 Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

, and

endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...

. 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. Common side effects include an upset stomach. Other side effects may include muscle or joint pains, shortness of breath, and liver problems. It appears to be safe during pregnancy and breastfeeding. It should not be used in those who are allergic to

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 ...

. It 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

class. It is similar in effect to

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 ...

and

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 ...

, being active against

penicillinase Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems ...

forming bacteria. Flucloxacillin was patented in 1961. It is not commonly used in the United States or Canada as of 2011.

Medical uses

Flucloxacillin is an

used to treat

, external ear infections, infections of leg ulcers,

diabetic foot infection Diabetic foot infection is any infection of the foot in a diabetic person. The most frequent cause of hospitalization for diabetic patients is due to foot infections. Symptoms may include pus from a wound, redness, swelling, pain, warmth, tachyca ...

s, and infection of bone.

Skin

Flucloxacillin is used for both ''

staphylococcal ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultati ...

'' and ''

streptococcal ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occur ...

'' skin infections.Stanway, Amy. These include

folliculitis Folliculitis is the infection and inflammation of one or more hair follicles. The condition may occur anywhere on hair-covered skin. The rash may appear as pimples that come to white tips on the face, chest, back, arms, legs, buttocks, or head. A ...

, carbuncles,

impetigo Impetigo is a bacterial infection that involves the superficial skin. The most common presentation is yellowish crusts on the face, arms, or legs. Less commonly there may be large blisters which affect the groin or armpits. The lesions may be pa ...

ecthyma Ecthyma( ec·thy·ma , \ ek-ˈthī-mə )is a variation of impetigo, presenting at a deeper level of tissue. It is usually associated with Group A (beta-hemolytic) Streptococcus (abbreviated GAS). See also * Ecthyma gangrenosum Ecthyma ...

cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of t ...

erysipelas Erysipelas () is a relatively common bacterial infection of the superficial layer of the skin ( upper dermis), extending to the superficial lymphatic vessels within the skin, characterized by a raised, well-defined, tender, bright red rash, t ...

necrotising fasciitis Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or p ...

, and infections of skin conditions such as

eczema Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thick ...

scabies Scabies (; also sometimes known as the seven-year itch) is a contagious skin infestation by the mite ''Sarcoptes scabiei''. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin ...

, ulcers and

acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

. 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 Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis ...

for more severe cellulitis. However, support for this practice has lessened since findings in a study published in the ''

Emergency Medicine Journal The ''Emergency Medicine Journal'' is a monthly peer-reviewed medical journal that is published by the BMJ Group on behalf of the Royal College of Emergency Medicine of which it is an official journal It is also an official journal of the Briti ...

'' in 2005 did not show this combination to give additional clinical benefit. In the UK, using flucloxacillin alone is the first choice for treating cellulitis. Some other countries vary. File:Impetigo2020.jpg, Impetigo File:Facial erysipelas.jpg, Erysipelas File:Folliculitis2.jpg, Folliculitis File:Cellulitis1.jpg, Cellulitis File:Carbuncle.jpg, Carbuncle

Wounds

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.

Bone

Despite having a lower than optimum drug penetration into bone ratio of 10–20%, flucloxacillin appears effective in treating

osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...

. Depending on local guidance it may be used in the treatment of infection of joints while waiting for culture results.

Other

It may be used in combination with other antibiotics to treat

and can be used to prevent infection before surgery, particularly heart, lung, or bone surgery. When used to treat

, in combination with other antibiotics or alone, the dose of flucloxacillin may need to exceed the usual dose.

Resistance

Despite flucloxacillin being insensitive to beta-lactamases, some organisms have developed resistance to it and other narrow-spectrum β-lactam antibiotics including

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 ...

. Such organisms include methicillin-resistant ''Staphylococcus aureus'', which has developed resistance to flucloxacillin and other penicillins by having an altered penicillin-binding protein.

Side effects

Common side effects associated with the use of flucloxacillin include:

diarrhoea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

and

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

at injection site,

superinfection A superinfection is a second infection superimposed on an earlier one, especially by a different microbial agent of exogenous or endogenous origin, that is resistant to the treatment being used against the first infection. Examples of this in bact ...

(including

candidiasis Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...

allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

, 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,

cephalosporin 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 ...

s, or

carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. ...

s. 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, though some studies suggest that this does not compromise flucloxacillin plasma concentrations in most circumstances. The UK's

National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...

recommends taking at least 30 minutes before food or at least 2 hours after.

Drug interactions

Flucloxacillin can reduce the excretion of

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

, 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 Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia. Probenecid was developed as an alternative to caronamide to competitive ...

Mechanism of action

Flucloxacillin is a narrow-spectrum

belonging to the

group of

s. It works by breaking down the bacterial cell wall. Like other β-lactam antibiotics, flucloxacillin

acts The Acts of the Apostles ( grc-koi, Πράξεις Ἀποστόλων, ''Práxeis Apostólōn''; la, Actūs Apostolōrum) is the fifth book of the New Testament; it tells of the founding of the Christian Church and the spread of its message ...

by inhibiting the synthesis of bacterial

cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...

s. It inhibits cross-linkage between the linear

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ...

polymer chains that make up a major component of the cell wall of

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...

bacteria. Flucloxacillin is more acid-stable than many other penicillins and can be given orally, in addition to

parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

routes. However, like

, it is less potent than

against non-β-lactamase-producing Gram-positive bacteria. Flucloxacillin has similar

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

, 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 An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...

than dicloxacillin, but a lower incidence of renal adverse effects.Rossi S, editor.

Australian Medicines Handbook Australian Medicines Handbook (AMH) is a peer-reviewed medicines prescribing guide for Australian health professionals. The handbook is available in paper and digital formats and is supplemented by the ''AMH Aged Care Companion'' and the ''AMH C ...

2006. Adelaide: Australian Medicines Handbook; 2006.

Chemistry

Flucloxacillin is insensitive to

beta-lactamase Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems ...

(also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence 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 ...

group on the

side chain In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a l ...

of the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of side chain

steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

. Thus, it is able to bind to

penicillin-binding protein 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 discov ...

s and inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.

History

Flucloxacillin was developed in the 1960s following an increase in penicillin-resistant (

producing) staphylococcal infections due to the widespread use of

by 1960. All the natural penicillins and first semi-synthetic penicillins were destroyed by staphylococcal beta-lactamase, leading Beecham (later

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...

) to search for more stable antibiotics. By 1962, a series of similarly structured acid-stable penicillins (

oxacillin Oxacillin (trade name Bactocill) is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham. It was patented in 1960 and approved for medical use in 1962. Medical uses Oxacillin is a penicillinase-resistant β ...

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. Flucloxacillin was first marketed in Europe in the 1970s.

Available forms

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

suspension Suspension or suspended may refer to: Science and engineering * Suspension (topology), in mathematics * Suspension (dynamical systems), in mathematics * Suspension of a ring, in mathematics * Suspension (chemistry), small solid particles suspend ...

s (125 mg/5 ml or 250 mg/5 ml), and injections (powder for reconstitution, 250, 500, 1000 and 2000 mg per vial). Flucloxacillin is not commonly used in the United States or Canada as of 2011. In several other countries however, it is supplied under a variety of trade names including Floxapen, Flopen, Flubex, Flupen, Phylopen, and Staphylex.

Combination

Flucloxacillin is combined with

ampicillin Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B strepto ...

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)

References

External links

* {{Portal bar , Medicine Penicillins Enantiopure drugs Hepatotoxins Isoxazoles Chloroarenes Fluoroarenes