Dicloxacillin
3850556
207412660
2008-04-22T18:17:38Z
WLU
2118749
redirect
{{drugbox
| IUPAC_name = (2''S'',5''R'',6''R'')-6-{[3-(2,6-dichlorophenyl)-5-methyl-<br>oxazole-4-carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-<br>1-azabicyclo[3.2.0]heptane-2-carboxylic acid
| image = Dicloxacillin.png
| CAS_number = 3116-76-5
| ATC_prefix = J01
| ATC_suffix = CF01
| PubChem = 18381
| DrugBank = APRD00916
| C = 19 |H = 17 |Cl = 2 |N = 3 |O = 5 |S = 1
| molecular_weight = 470.327 [[Gram|g]]/[[Mole (unit)|mol]]
| bioavailability = 60 to 80%
| protein_bound = 98%
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 0.7 hours
| excretion = [[Kidney|Renal]] and biliary
| pregnancy_AU = B2
| pregnancy_US = B
| legal_AU = S4
| legal_US = Rx-only
| routes_of_administration = Oral
}}
'''Dicloxacillin''' ([[International Nonproprietary Name|INN]]) is a [[narrow-spectrum antibiotic|narrow spectrum]] [[beta-lactam antibiotic]] of the [[penicillin]] class. 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 [[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''' ([[Bristol-Myers Squibb|BMS]]).
==Mode of action==
{{main|Beta-lactam antibiotic}}
Like other β-lactam antibiotics, dicloxacillin acts by inhibiting the synthesis of bacterial [[cell wall]]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.
==Medicinal chemistry==
Dicloxacillin is insensitive to [[beta-lactamase]] (also known as penicillinase) enzymes secreted by many penicillin-resistant bacteria. The presence of the [[isoxazole|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 protein]]s (PBPs) and inhibit [[peptidoglycan]] 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 [[parenteral]] 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 effect (medicine)|adverse effects]] 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 [[capsule]]s (250 or 500 [[milligrams|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)
*[[Staphylococcus|Staphylococcal skin infections]] and [[cellulitis]] – including [[impetigo]], [[otitis externa]], [[folliculitis]], [[boil]]s, [[carbuncles]], and [[mastitis]]
*[[Pneumonia]] (adjunct)
*[[Osteomyelitis]], [[septic arthritis]]
*[[Septicaemia]]
*[[Empirical]] treatment for [[endocarditis]]
*Surgical [[prophylaxis]]
===Precautions/contraindications===
Dicloxacillin is contraindicated in those with a previous history of allergy to [[penicillin]]s, [[cephalosporin]]s or [[carbapenem]]s. It should also not be used in the eye, or those with a history of [[cholestasis|cholestatic hepatitis]] associated with the use of dicloxacillin or dicloxacillin. (Rossi, 2006)
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 reaction]]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)
Rarely, [[cholestasis|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)
==Resistance==
Despite dicloxacillin 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|methicillin-resistant ''Staphylococcus aureus'']] (MRSA).
==See also==
*[[Beta-lactam antibiotic]]
*[[Flucloxacillin]]
==References==
*Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.
{{PenicillinAntiBiotics}}
[[Category:Beta-lactam antibiotics]]
[[Category:Isoxazoles]]
[[es:Dicloxacilina]]
[[pt:Dicloxacilina]]
[[th:ไดคลอกซาซิลลิน]]