Dicloxacillin vs Cloxacillin for Treating Staphylococcus aureus Infections
Dicloxacillin is the preferred choice over cloxacillin for treating Staphylococcus aureus infections due to its superior oral bioavailability and pharmacokinetic profile. 1, 2
Comparison of Key Properties
- Both dicloxacillin and cloxacillin are penicillinase-resistant penicillins (isoxazolyl penicillins) that are effective against methicillin-susceptible Staphylococcus aureus (MSSA) 3
- Dicloxacillin has better oral bioavailability compared to cloxacillin, resulting in higher serum levels when administered orally 2
- Both antibiotics have similar spectrum of activity against Gram-positive bacteria, particularly Staphylococcus aureus 3, 4
- Both require QID (four times daily) dosing, which may affect patient compliance 5
- Both are considered narrow-spectrum antibiotics, which is advantageous for antimicrobial stewardship 5, 6
Clinical Applications
Mild Infections
- Dicloxacillin is specifically recommended by IDSA guidelines for mild diabetic foot infections caused by Staphylococcus aureus 5
- Both dicloxacillin and cloxacillin are listed as first-choice antibiotics for mild skin and soft tissue infections by WHO's Essential Medicines list 5
- For impetigo and ecthyma, dicloxacillin is recommended when S. aureus is suspected or confirmed 5
Moderate to Severe Infections
- For more severe infections, parenteral therapy is typically preferred, with options including vancomycin, linezolid, or daptomycin for MRSA 5
- For MSSA bacteremia and endocarditis, nafcillin or oxacillin are often preferred in the inpatient setting, though dicloxacillin and cloxacillin remain options for step-down therapy 4, 7
Pharmacokinetic Differences
- Dicloxacillin produces higher free serum levels compared to cloxacillin when administered orally 2
- The protein binding of dicloxacillin and cloxacillin is similar, but dicloxacillin generally achieves higher total serum concentrations 2
- Both drugs have similar half-lives and require dosing every 6 hours 1, 6
Special Considerations
- For patients with penicillin allergies (non-anaphylactic), first-generation cephalosporins like cephalexin are alternatives 3
- For patients with immediate hypersensitivity to penicillins, clindamycin is often recommended as an alternative 3
- Neither dicloxacillin nor cloxacillin is effective against MRSA; alternative agents should be used when MRSA is suspected 5
- For community-acquired MRSA infections, recommended alternatives include trimethoprim-sulfamethoxazole, doxycycline, clindamycin, or linezolid 5
Clinical Decision Making
- Choose dicloxacillin for outpatient treatment of MSSA infections due to better oral bioavailability 1, 2
- Consider local resistance patterns when selecting either agent 5
- For severe infections requiring hospitalization, parenteral therapy with nafcillin, oxacillin, or cefazolin may be preferred initially 4, 7
- Duration of therapy typically ranges from 7-14 days for uncomplicated skin and soft tissue infections but should be extended for more serious infections like endocarditis or osteomyelitis 5
Common Pitfalls and Caveats
- Neither dicloxacillin nor cloxacillin should be used empirically when MRSA prevalence is high in the community 5
- Poor compliance with QID dosing can lead to treatment failure; emphasize the importance of adherence 5
- Monitoring for hepatotoxicity is recommended with prolonged use of either agent 4
- Both drugs may have reduced absorption when taken with food; advise patients to take on an empty stomach when possible 1