Oral Alternatives to Oxacillin
For methicillin-susceptible staphylococcal infections requiring oral therapy, dicloxacillin 500 mg four times daily is the oral agent of choice in adults, while cephalexin 500 mg four times daily is the preferred alternative for penicillin-allergic patients (except those with immediate hypersensitivity reactions). 1
Primary Oral Alternatives
First-Line Options for MSSA
- Dicloxacillin is explicitly designated as the "oral agent of choice for methicillin-susceptible strains in adults" at 500 mg four times daily 1, 2
- Cephalexin 500 mg four times daily serves as the preferred alternative for penicillin-allergic patients without immediate hypersensitivity reactions 1
- Both agents should be taken on an empty stomach (at least 1 hour before or 2 hours after meals) with at least 4 fluid ounces of water 2
Pediatric Dosing
- Dicloxacillin: 25-50 mg/kg/day divided into 4 doses for mild-to-moderate infections; 25 mg/kg/day for severe infections (in children <40 kg) 1, 2
- Cephalexin: 25-50 mg/kg/day divided into 4 doses, with the advantage of suspension availability and less frequent dosing requirements compared to dicloxacillin 1
Secondary Oral Alternatives
When first-line agents cannot be used due to allergy, intolerance, or resistance patterns:
Clindamycin 300-450 mg four times daily (adults) or 20-30 mg/kg/day in 3 divided doses (children) 1
Doxycycline or minocycline 100 mg twice daily (adults only; not recommended for children <8 years) 1
- Bacteriostatic with limited recent clinical experience 1
Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily (adults) or 8-12 mg/kg/day based on trimethoprim component (children) 1
- Bactericidal but with limited published efficacy data for staphylococcal infections 1
Clinical Context and Equivalency
The IDSA guidelines from 2014 note that "there are no important differences in therapeutic effect among oxacillin, cloxacillin, dicloxacillin or flucloxacillin by the oral route" 3, establishing therapeutic equivalence among these penicillinase-resistant penicillins when given orally.
Critical Limitations
- Oral penicillinase-resistant penicillins should not be used as initial therapy in serious, life-threatening infections 2
- Oral therapy may be used to follow up previous parenteral therapy once clinical condition warrants 2
- For cellulitis specifically, a penicillinase-resistant semisynthetic penicillin or first-generation cephalosporin is recommended (Class A-I evidence) 1
Important Caveats
- All oral alternatives are completely ineffective against MRSA and should never be used if methicillin resistance is suspected or confirmed 1
- Dicloxacillin should not be taken in the supine position or immediately before bed due to risk of esophageal irritation 2
- Duration of therapy varies but should continue for at least 48 hours after the patient becomes afebrile and asymptomatic with negative cultures 2
- For severe infections like endocarditis and osteomyelitis, therapy should continue for at least 14 days and may require longer duration 2