Dicloxacillin
Encyclopedia
Dicloxacillin is a narrow-spectrum beta-lactam antibiotic
of the penicillin
class. It is used to treat infections caused by susceptible Gram-positive
bacteria
. It is active against beta-lactamase
-producing organisms such as Staphylococcus aureus
, which would otherwise be resistant to most penicillin
s. It is very similar to flucloxacillin
and these two agents are considered interchangeable. Dicloxacillin is available under a variety of trade names including Diclocil (BMS
).
s. It inhibits cross-linkage between the linear peptidoglycan
polymer chains that make up a major component of the cell wall of Gram-positive
bacteria.
(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.
routes. However, like methicillin
, it is less potent than benzylpenicillin
against non-β-lactamase-producing Gram-positive
bacteria.
Dicloxacillin has similar pharmacokinetics
, antibacterial activity, and indications to flucloxacillin, and the two agents are considered interchangeable. It is believed to have lower incidence of severe hepatic adverse effects
than flucloxacillin, but a higher incidence of renal adverse effects. (Rossi, 2006)
s, cephalosporin
s or carbapenem
s. 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.
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)
s (ADRs) associated with the use of dicloxacillin 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)
On rare occasions, cholestatic jaundice
(also referred to as cholestatic hepatitis) has been associated with dicloxacillin 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)
(MRSA).
Beta-lactam antibiotic
β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems...
of the penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
class. It is used to treat infections caused by susceptible Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. It is active against beta-lactamase
Beta-lactamase
Beta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
-producing organisms such as Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
, which would otherwise be resistant to most penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
s. It is very similar to flucloxacillin
Flucloxacillin
Flucloxacillin or floxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus...
and these two agents are considered interchangeable. Dicloxacillin is available under a variety of trade names including Diclocil (BMS
Bristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
).
Mode of action
Like other β-lactam antibiotics, dicloxacillin acts by inhibiting the synthesis of bacterial cell wallCell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
s. It inhibits cross-linkage between the linear peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...
polymer chains that make up a major component of the cell wall of Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria.
Medicinal chemistry
Dicloxacillin is insensitive to beta-lactamaseBeta-lactamase
Beta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
(also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the isoxazolyl
Isoxazole
Isoxazole is an azole with an oxygen atom next to the nitrogen. It is also the class of compounds containing this ring.Isoxazole rings are found in some natural products, such as ibotenic acid. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib...
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
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...
crosslinking, but is not bound by or inactivated by β-lactamases.
Clinical use
Dicloxacillin is more acid-stable than many other penicillins and can be given orally, in addition to parenteralParenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
routes. However, like methicillin
Methicillin
Meticillin or methicillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline.-History:Methicillin was developed by Beecham in 1959...
, it is less potent than benzylpenicillin
Benzylpenicillin
Benzylpenicillin, commonly known as penicillin G, is the gold standard type of penicillin. 'G' in the name 'Penicillin G' refers to 'Gold Standard'. Penicillin G is typically given by a parenteral route of administration because it is unstable in the hydrochloric acid of the stomach...
against non-β-lactamase-producing Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria.
Dicloxacillin has similar pharmacokinetics
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
, antibacterial activity, and indications to flucloxacillin, and the two agents are considered interchangeable. It is believed to have lower incidence of severe hepatic adverse effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired 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. If it results from an unsuitable or incorrect dosage or...
than flucloxacillin, but a higher incidence of renal adverse effects. (Rossi, 2006)
Available forms
Dicloxacillin is commercially available as the sodium salt dicloxacillin sodium in capsules (250 or 500 mg) and injections (powder for reconstitution, 500 and 1000 mg per vial).Indications
Dicloxacillin is indicated for the treatment of infections caused by susceptible bacteria. Specific approved indications include: (Rossi, 2006)- Staphylococcal skin infectionsStaphylococcusStaphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
and cellulitisCellulitisCellulitis is a diffuse inflammation of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken: cracks in the skin, cuts, blisters,...
– including impetigoImpetigoImpetigo is a highly contagious bacterial skin infection most common among pre-school children. People who play close contact sports such as rugby, American football and wrestling are also susceptible, regardless of age. Impetigo is not as common in adults. The name derives from the Latin impetere...
, otitis externaOtitis externaOtitis externa is an inflammation of the outer ear and ear canal. Along with otitis media, external otitis is one of the two human conditions commonly called "earache". It also occurs in many other species. Inflammation of the skin of the ear canal is the essence of this disorder...
, folliculitisFolliculitisFolliculitis is the inflammation of one or more hair follicles. The condition may occur anywhere on the skin with the exception of the palms of the hands and soles of the feet.- Causes :...
, boilBoilA boil, also called a furuncle, is a deep folliculitis, infection of the hair follicle. It is always caused by infection by the bacterium Staphylococcus aureus, resulting in a painful swollen area on the skin caused by an accumulation of pus and dead tissue...
s, carbuncles, and mastitisMastitisMastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:... - PneumoniaPneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
(adjunct) - OsteomyelitisOsteomyelitisOsteomyelitis simply means an infection of the bone or bone marrow...
, septic arthritisSeptic arthritisSeptic arthritis is the purulent invasion of a joint by an infectious agent which produces arthritis. People with artificial joints are more at risk than the general population but have slightly different symptoms, are infected with different organisms and require different treatment. Septic...
, throat infections, streptococcus - Septicaemia
- EmpiricalEmpiricalThe word empirical denotes information gained by means of observation or experimentation. Empirical data are data produced by an experiment or observation....
treatment for endocarditisEndocarditisEndocarditis 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 even on intracardiac devices... - Surgical prophylaxis
Precautions/contraindications
Dicloxacillin is contraindicated in those with a previous history of allergy to penicillinPenicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
s, cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
s or carbapenem
Carbapenem
Carbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...
s. It should also not be used in the eye, or those with a history of cholestatic hepatitis
Cholestasis
In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of...
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. (Rossi, 2006)
Adverse effects
Common adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s (ADRs) associated with the use of dicloxacillin include: diarrhoea, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, rash
Rash
A rash is a change of the 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, cracked or blistered, swell and may be painful. The causes, and...
, urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
and inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
at injection site, superinfection
Superinfection
In virology, superinfection is the process by which a cell, that has previously been infected by one virus, gets coinfected with a different strain of the virus, or another virus at a later point in time. Viral superinfections of serious conditions can lead to resistant strains of the virus, which...
(including candidiasis
Candidiasis
Thrush redirects here. For the hoof infection see Thrush .Candidiasis or thrush is a fungal infection of any of the Candida species , of which Candida albicans is the most common...
), allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
, and transient increases in liver enzymes and bilirubin. (Rossi, 2006)
On rare occasions, cholestatic jaundice
Cholestasis
In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of...
(also referred to as cholestatic hepatitis) has been associated with dicloxacillin 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)
Resistance
Despite dicloxacillin's 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 aureusMethicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA).
See also
- Beta-lactam antibioticBeta-lactam antibioticβ-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems...
- FlucloxacillinFlucloxacillinFlucloxacillin or floxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible Gram-positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus...
- AmoxicillinAmoxicillinAmoxicillin , formerly amoxycillin , and abbreviated amox, is a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral...
(formerly BeechamBeecham (pharmaceutical company)Beecham was a British pharmaceutical company. It was once a constituent of the FTSE 100 Index. Beecham, after having merged with SmithKline Beckman, merged with GlaxoWellcome to become GlaxoSmithKline .-History:...
, now GlaxoSmithKlineGlaxoSmithKlineGlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
)