What is dicloxacillin?

What is Dicloxacillin?

Dicloxacillin is a semisynthetic, penicillinase-resistant penicillin antibiotic used specifically to treat infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) and other susceptible Gram-positive bacteria. 1, 2

Drug Classification and Mechanism

• Dicloxacillin belongs to the isoxazolyl penicillin class of antibiotics, which are stable against bacterial penicillinases (beta-lactamases produced by staphylococci). 3, 4
• It exhibits bactericidal activity by inhibiting bacterial cell wall synthesis, similar to other beta-lactam antibiotics. 5
• The drug demonstrates antimicrobial activity against a wide variety of Gram-positive bacteria while maintaining stability against penicillinases. 3

Spectrum of Activity

Susceptible Organisms

• Staphylococcus aureus (methicillin-susceptible strains only, including penicillinase-producing strains). 1, 2
• Streptococcus pyogenes (Group A beta-hemolytic streptococci). 1, 4
• Coagulase-negative Staphylococcus species. 3
• Other streptococcal species including S. pneumoniae, S. epidermidis, S. viridans, and S. agalactiae. 4

Critical Limitation

• Dicloxacillin has ZERO activity against methicillin-resistant Staphylococcus aureus (MRSA) and must never be used when MRSA is suspected or confirmed. 2, 6

Clinical Indications

Skin and Soft Tissue Infections

• Impetigo: 250 mg four times daily orally in adults. 1
• Non-purulent cellulitis: 500 mg four times daily orally for empirical coverage of beta-hemolytic streptococci. 2
• Mild diabetic foot infections: 500 mg four times daily orally. 1, 2
• Uncomplicated MSSA skin infections in adults and children. 1, 2

Osteoarticular Infections

• Chronic suppression therapy for MSSA osteomyelitis after initial intravenous treatment: 500 mg four times daily orally. 2
• Indefinite chronic antimicrobial suppression for prosthetic joint infections caused by oxacillin-sensitive staphylococci: 500 mg three or four times daily orally. 2

Important Contraindication

• Do NOT use dicloxacillin for purulent cellulitis or abscesses as monotherapy, as these infections are frequently caused by community-acquired MRSA; use clindamycin, doxycycline, or trimethoprim-sulfamethoxazole instead. 2

Dosing Regimens

Adults

• Standard dosing: 250-500 mg orally four times daily (every 6 hours). 1, 2
• Severe infections: 500 mg orally four times daily. 1, 2
• Take on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. 5

Pediatrics

• 12-25 mg/kg/day divided into 4 doses for mild to moderate infections. 2
• Not commonly used in pediatric practice compared to cephalexin due to dosing frequency. 1

Pharmacokinetics

• Bioavailability: Dicloxacillin has superior oral bioavailability compared to cloxacillin within the anti-staphylococcal penicillin class. 1, 2
• Peak concentrations: Achieved 0.5-2 hours after oral administration. 4
• Half-life: Approximately 1.4-1.7 hours. 4
• Renal excretion: 38-50% excreted unchanged in urine. 4
• Dose proportionality: Linear pharmacokinetics with dose-proportional increases in maximum concentration and area under the curve. 4
• No accumulation: Multiple dosing does not lead to drug accumulation. 4

Comparative Efficacy

• Dicloxacillin vs. Cephalexin: Both are equally effective for staphylococcal skin infections, though cephalexin offers the convenience of twice-daily dosing compared to dicloxacillin's four-times-daily requirement. 7
• Dicloxacillin vs. Cloxacillin: Dicloxacillin achieves serum levels approximately 2-3 times higher than cloxacillin, potentially allowing longer dosing intervals. 8

Important Precautions and Warnings

Allergy Considerations

• Cross-allergenicity exists with other beta-lactam antibiotics including cephalosporins and carbapenems. 5
• Patients with previous anaphylactic reactions to penicillin should wear medical identification tags. 5
• Discontinue immediately if allergic reactions occur unless the condition is life-threatening and amenable only to penicillin therapy. 5

Administration Limitations

• Do not rely on oral administration in patients with severe illness, nausea, vomiting, gastric dilation, or intestinal hypermotility, as therapeutic absorption may not occur. 5

Drug Interactions

• Tetracyclines may antagonize the bactericidal effect of dicloxacillin; avoid concurrent use. 5
• Probenecid increases and prolongs serum penicillin levels when administered concomitantly. 5
• Aminoglycosides are physically/chemically incompatible with dicloxacillin and can be inactivated in vitro; administer separately. 5
• May reduce anticoagulant response to dicumarol and warfarin. 5

Monitoring Requirements

• Bacteriologic cultures should be obtained to confirm staphylococcal infection and susceptibility. 5
• Periodic assessment of renal, hepatic, and hematopoietic function during prolonged therapy. 5
• Blood cultures, white blood cell counts, and differential counts should be obtained before therapy and at least weekly during treatment. 5
• Monitor AST/ALT values periodically for possible liver function abnormalities. 5
• Adjust dosage if renal impairment is present to avoid neurotoxic reactions. 5

Antimicrobial Stewardship

• Complete the entire prescribed course even if symptoms improve, to prevent treatment failure and development of antibiotic resistance. 5
• Prescribing dicloxacillin without proven or strongly suspected bacterial infection increases the risk of drug-resistant bacteria. 5
• Monte Carlo simulation studies suggest 250 mg every 6 hours or 500 mg every 6 hours are optimal regimens for community-onset infections, achieving >90% cumulative fraction of response against MSSA, coagulase-negative Staphylococcus, and other Streptococcus isolates. 3

Safety Profile

• Generally safe and well-tolerated in clinical studies. 4
• Adverse events are typically mild. 4
• Clostridium difficile-associated diarrhea can occur even 2+ months after the last dose; contact physician immediately if watery/bloody stools develop. 5
• Common side effects may include nausea, vomiting, diarrhea, skin rash, and black tongue. 5