Cloxacillin Oral Dosing for Skin and Soft Tissue Infections
For adults with bacterial skin or soft tissue infections, cloxacillin should be dosed at 500 mg orally four times daily (every 6 hours), though it is important to note that cloxacillin has been largely replaced by its isomer dicloxacillin in modern practice, which uses the same dosing regimen. 1
Standard Adult Dosing
- 500 mg orally four times daily (every 6 hours) is the established dose for methicillin-susceptible staphylococcal and streptococcal skin infections 1
- Treatment duration is typically 7 days, depending on clinical response 1
- This dosing applies to infections such as cellulitis, impetigo, folliculitis, furuncles, and infected wounds 1
Pediatric Dosing
- 25 mg/kg/day divided into 4 doses (every 6 hours) for children 1
- Doses listed are not appropriate for neonates; refer to specialized pediatric infectious disease references for neonatal dosing 1
Clinical Context and Coverage
- Cloxacillin (and its isomer dicloxacillin) is the oral agent of choice for methicillin-susceptible Staphylococcus aureus (MSSA) skin infections 1
- It provides excellent coverage against both staphylococci and streptococci, the most common pathogens in primary skin infections 2
- Cloxacillin is completely inactive against methicillin-resistant S. aureus (MRSA) and should not be used if MRSA is suspected 1
Important Considerations for Dosing Adjustments
Renal Function
- While the guidelines do not specify dose adjustments for renal impairment with cloxacillin, caution is warranted in severe renal dysfunction
- Consider alternative agents or consult nephrology for patients with creatinine clearance <10 mL/min
Age-Related Factors
- Standard adult dosing applies to patients ≥18 years 3
- For elderly patients, no specific dose reduction is typically required unless renal function is significantly impaired
Weight Considerations
- Standard dosing (500 mg four times daily) is appropriate for most adult weights
- Pediatric dosing is weight-based at 25 mg/kg/day 1
When to Choose Cloxacillin vs. Alternatives
Use cloxacillin when:
- MSSA is confirmed or strongly suspected 1
- Patient has no penicillin allergy 1
- Local MRSA prevalence is low and infection characteristics suggest MSSA 2
Avoid cloxacillin and use alternatives when:
- MRSA is suspected (use clindamycin, trimethoprim-sulfamethoxazole, or doxycycline instead) 1
- Patient has immediate hypersensitivity to penicillins 1
- Infection involves animal or human bites (use amoxicillin-clavulanate for broader anaerobic and Pasteurella coverage) 1
- Patient has severe immunocompromise requiring broader coverage 1
Comparative Efficacy
- Clinical studies show cloxacillin achieves cure rates of approximately 60-78% for skin and soft tissue infections 3, 4
- Cloxacillin demonstrates high sensitivity (93%) against S. aureus in primary pyodermas 2
- However, S. aureus shows 89.5% resistance to penicillin/ampicillin, making cloxacillin's beta-lactamase stability crucial 2
Common Pitfalls to Avoid
- Do not underdose: The full 500 mg four times daily is necessary for adequate tissue penetration; lower doses risk treatment failure 1
- Do not use for MRSA: Cloxacillin has zero activity against MRSA; empiric use in areas with high MRSA prevalence (>10-15%) is inappropriate 1, 2
- Do not combine with ampicillin routinely: The combination of ampicillin and cloxacillin has limited utility except for specific situations like cellulitis with mixed flora 2
- Do not extend beyond 7 days without reassessment: If no improvement by day 5-7, consider inadequate source control, resistant organisms, or alternative diagnosis 1