Dicloxacillin

Dicloxacillin

Systematic (IUPAC) name
(2S,5R,6R)-6-{[3-(2,6-dichlorophenyl)-5-methyl- oxazole-4-carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia- 1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a685017
Pregnancy cat.	B2(AU) B(US)
Legal status	Prescription Only (S4) (AU) ℞-only (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	60 to 80%
Protein binding	98%
Metabolism	Hepatic
Half-life	0.7 hours
Excretion	Renal and biliary
Identifiers
CAS number	3116-76-5 Y
ATC code	J01CF01 QJ51CF01
PubChem	CID 18381
DrugBank	APRD00916
ChemSpider	17358 Y
UNII	COF19H7WBK Y
KEGG	D02348 Y
ChEBI	CHEBI:4511 Y
ChEMBL	CHEMBL893 Y
Chemical data
Formula	C19H17Cl2N3O5S
Mol. mass	470.327 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C19H17Cl2N3O5S/c1-7-10(12(23-29-7)11-8(20)5-4-6-9(11)21)15(25)22-13-16(26)24-14(18(27)28)19(2,3)30-17(13)24/h4-6,13-14,17H,1-3H3,(H,22,25)(H,27,28)/t13-,14+,17-/m1/s1 Y Key:YFAGHNZHGGCZAX-JKIFEVAISA-N Y
N(what is this?)  (verify)

Dicloxacillin (INN) 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,^[1] which would otherwise be resistant to most penicillins. 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).

Mode of action

Main article: Beta-lactam antibiotic

Like other β-lactam antibiotics, dicloxacillin 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.

Medicinal chemistry

Dicloxacillin 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.

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

Precautions/contraindications

Dicloxacillin 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.

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 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)

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 aureus (MRSA).

See also

• Beta-lactam antibiotic
• Flucloxacillin
• Amoxicillin (formerly Beecham, now GlaxoSmithKline)

References

1. ^ Miranda-Novales G, Leaños-Miranda BE, Vilchis-Pérez M, Solórzano-Santos F (2006). "In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains". Ann. Clin. Microbiol. Antimicrob. 5: 25. doi:10.1186/1476-0711-5-25. PMC 1617116. PMID 17034644. http://www.ann-clinmicrob.com/content/5//25. 

• Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.