Dicloxacillin

Dicloxacillin

Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a685017
Pregnancy category	AU: B2 US: B (No risk in non-human studies)
Routes of administration	Oral
ATC code	J01CF01 (WHO) QJ51CF01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	60 to 80%
Protein binding	98%
Metabolism	Hepatic
Biological half-life	0.7 hours
Excretion	Renal and biliary
Identifiers
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
CAS Number	3116-76-5 Y
PubChem (CID)	18381
DrugBank	DB00485 Y
ChemSpider	17358 Y
UNII	COF19H7WBK Y
KEGG	D02348 Y
ChEBI	CHEBI:4511 Y
ChEMBL	CHEMBL893 Y
ECHA InfoCard	100.019.535
Chemical and physical data
Formula	C19H17Cl2N3O5S
Molar mass	470.327 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O)c2c(onc2c1c(Cl)cccc1Cl)C)[C@H]4SC3(C)C
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
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Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class.^[1] It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria.^[1] It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).^[2]

Medical uses

Dicloxacillin is used to treat mild-to-moderate staphylococcal infections.^[3] To decrease the development of resistance, dicloxacillin is recommended to treat infections that are suspected or proven to be caused by beta-lactamase-producing bacteria.^[3]

Dicloxacillin is similar in pharmacokinetics, antibacterial activity, and indications to flucloxacillin, and the two agents are considered interchangeable.^[4] It is believed to have lower incidence of severe hepatic adverse effects than flucloxacillin, but a higher incidence of renal adverse effects.^[4]

Dicloxacillin is used for the treatment of infections caused by susceptible bacteria. Specific approved indications include:^[4]

• 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

Available forms

Dicloxacillin is commercially available as the sodium salt, dicloxacillin sodium, in capsules and as a powder for reconstitution.^[1][5]

Contraindications

Dicloxacillin is contraindicated in those with a previous history of allergy (hypersensitivity/anaphylactic reaction) to any penicillins.^[1][6]

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.^[4]

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 over 55 years old, females, and those with treatment longer than 2 weeks.^[4]

It should be used with caution and monitored in the elderly, particularly with intravenous administration, due to a risk of thrombophlebitis.^[1]

Interactions

Dicloxacillin has potential interactions with following drugs:

• Warfarin^[7]
• Methotrexate^[8]
• Tetracyclines^[9]

Resistance

Despite dicloxacillin 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 (MRSA).^[10]

Mechanism of action

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-lactamase

See also

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

References

1. 1 2 3 4 5 Product Information: DICLOXACILLIN SODIUM-dicloxacillin sodium capsule. Teva Pharmaceuticals USA Inc, Revised 8/2015
2. ↑ Miranda-Novales, G; Leaños-Miranda, BE; Vilchis-Pérez, M; Solórzano-Santos, F (12 October 2006). "In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains.". Annals of Clinical Microbiology and Antimicrobials. 5: 25. doi:10.1186/1476-0711-5-25. PMC 1617116. PMID 17034644. 
3. 1 2 "Dicloxacillin". livertox.nih.gov. Retrieved 2015-11-05.
4. 1 2 3 4 5 Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006
5. ↑ "Dicloxacillin: MedlinePlus Drug Information". www.nlm.nih.gov. Retrieved 2015-11-05.
6. ↑ "DailyMed - DICLOXACILLIN SODIUM- dicloxacillin sodium capsule". dailymed.nlm.nih.gov. Retrieved 2015-11-05.
7. ↑ Lacey, CS (May 2004). "Interaction of dicloxacillin with warfarin.". The Annals of pharmacotherapy. 38 (5): 898. doi:10.1345/aph.1d484. PMID 15054148. 
8. ↑ Ronchera, CL; Hernández, T; Peris, JE; Torres, F; Granero, L; Jiménez, NV; Plá, JM (October 1993). "Pharmacokinetic interaction between high-dose methotrexate and amoxycillin.". Therapeutic drug monitoring. 15 (5): 375–9. doi:10.1097/00007691-199310000-00004. PMID 8249043. 
9. ↑ Moellering RC, Jr (29 August 1983). "Rationale for use of antimicrobial combinations.". The American Journal of Medicine. 75 (2A): 4–8. PMID 6351605. 
10. ↑ Rosdahl, VT; Frimodt-Møller, N; Bentzon, MW (August 1989). "Resistance to dicloxacillin, methicillin and oxacillin in methicillin-susceptible and methicillin-resistant Staphylococcus aureus detected by dilution and diffusion methods.". APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 97 (8): 715–22. PMID 2669854.