Diclocil®

Dicloxacillin · oral capsule

Antibiotic

Approved uses

Infections caused by penicillinase-producing staphylococci that have demonstrated susceptibility

Adults 125 mg every 6 hours for mild to moderate infection, 250 mg every 6 hours for severe infection; children under 40 kg 12.5 mg/kg/day or 25 mg/kg/day for severe infection, in equally divided doses every 6 hours.

OFF-LABELNot in the FDA label for this product

Preseptal cellulitis due to methicillin-susceptible Staphylococcus aureus

IDSA skin and soft tissue infection regimen for methicillin-susceptible S. aureus: adults 500 mg orally four times daily; children 25 to 50 mg/kg/day orally in 4 divided doses.

Guideline · no ocular trials

No trial in preseptal cellulitis was found on PubMed. The IDSA skin and soft tissue infection guideline names this the oral agent of choice for methicillin-susceptible strains in adults and states it is inactive against MRSA; the dose shown is that guideline's recommendation for staphylococcal skin and soft tissue infection generally, not a preseptal cellulitis regimen, and it is higher than the label's own severe-infection dose of 250 mg every 6 hours. Coverage is the practical limit: in a 10-year retrospective review of 90 ocular MRSA isolates from 75 patients at one Hong Kong center, preseptal cellulitis was the most common community-associated MRSA presentation, and MRSA accounted for a mean 12.9% of ocular S. aureus infections per year at that center.

Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52 (practice guideline). PMID 24973422. Ocular MRSA epidemiology: Wong ES, Chow CWY, Luk WK, Fung KSC, Li KKW. A 10-Year Review of Ocular Methicillin-Resistant Staphylococcus aureus Infections: Epidemiology, Clinical Features, and Treatment. Cornea. 2017;36(1):92-97 (retrospective case review). PMID 27755189.

Contraindications

Hypersensitivity to any of the penicillins or to any component of the formulation.

Available Forms

250 mg and 500 mg capsules

Mechanism of Action

Penicillinase-resistant semisynthetic penicillin; bactericidal against susceptible organisms during active multiplication by inhibiting bacterial cell wall biosynthesis. Resistance to staphylococcal penicillinase preserves activity against beta-lactamase producing methicillin-susceptible staphylococci, but the drug is inactive against MRSA.

Warnings & Precautions

Anaphylaxis: Anaphylactic shock occurs in 0.015% to 0.04% of all penicillin-treated patients, and shock resulting in death has occurred in approximately 0.002% of patients treated; more frequent after parenteral administration but reported on oral penicillins.
Beta-lactam cross-allergenicity: Clinical and laboratory evidence of partial cross-allergenicity among penicillins, cephalosporins, cephamycins and other 1-oxa-beta-lactams; a history of penicillin hypersensitivity may also produce a reaction to a cephalosporin.
Aqueous humor penetration: At normal doses only insignificant concentrations are found in the aqueous humor and cerebrospinal fluid.
MRSA resistance: Inactive against methicillin-resistant S. aureus; preseptal cellulitis was the most common community-associated MRSA presentation in a 10-year single-center ocular MRSA series.
Clostridium difficile associated diarrhea: Ranges from mild diarrhea to fatal colitis, may be refractory and require colectomy, and has been reported more than 2 months after antibacterial administration.
Oral route limits: Not for initial therapy of serious, life-threatening infection, and not to be relied on in severe illness, nausea, vomiting, gastric dilatation, cardiospasm or intestinal hypermotility.
Prolonged therapy monitoring: Periodic assessment of renal, hepatic and hematopoietic function; blood cultures with white cell and differential counts before therapy and at least weekly during it, plus periodic urinalysis, BUN and creatinine.
Anticoagulant interaction: May reduce the anticoagulant response to dicumarol and warfarin; monitor prothrombin times and adjust the anticoagulant dose.
Tetracycline antagonism: Tetracycline may antagonize the bactericidal effect of penicillin, and concurrent use should be avoided.

Common Side Effects

Hypersensitivity: Reported incidence of allergic reactions to penicillin 0.7% to 10%; immediate reactions within 20 minutes range from urticaria and pruritus to angioedema, laryngospasm, bronchospasm, hypotension and vascular collapse, and the anaphylactic form is very rare and usually follows parenteral therapy though it has occurred on oral therapy.
Accelerated reactions: Urticaria, pruritus and fever 20 minutes to 48 hours after a dose, occasionally with laryngeal edema, laryngospasm or hypotension; fatality is uncommon.
Delayed reactions: After 48 hours and as late as 2 to 4 weeks, serum sickness-like fever, malaise, urticaria, myalgia, arthralgia and abdominal pain, plus various skin rashes.
Gastrointestinal: Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue; pseudomembranous colitis has been reported with this agent.
Esophageal injury: Postmarketing reports of esophageal burning, esophagitis and esophageal ulceration, particularly after capsules taken with too little water or before lying down.
Hematologic: Eosinophilia, hemolytic anemia, agranulocytosis, neutropenia, leukopenia, granulocytopenia, thrombocytopenia and bone marrow depression, reported across the penicillinase-resistant penicillins.
Hepatic: Asymptomatic transient rises in alkaline phosphatase, AST and ALT; the label attributes the hepatotoxicity syndrome of fever, nausea and vomiting with abnormal liver tests to oxacillin and cloxacillin, and reports cholestatic hepatitis rarely.
Renal: Renal tubular damage and interstitial nephritis are attributed on this label to methicillin and, infrequently, to nafcillin and oxacillin.
Neurotoxicity: Lethargy, confusion, twitching, multifocal myoclonus and epileptiform seizures, reported with large intravenous doses of penicillinase-resistant penicillins and especially in renal insufficiency.

Pregnancy & Lactation

Pregnancy: Reproduction studies in mouse, rat and rabbit showed no impaired fertility or fetal harm from penicillinase-resistant penicillins, and human experience with penicillins in pregnancy has shown no positive evidence of adverse fetal effects; there are no adequate or well-controlled studies in pregnant women, so use only if clearly needed.

Lactation: Penicillins are excreted in breast milk; exercise caution in a nursing woman.

Pediatric Use

No dose is recommended for the newborn; experience in the neonatal period is limited.