What is the recommended treatment approach for a patient with a severe skin infection using Augmentin (amoxicillin-clavulanate) and doxycycline together?

Augmentin and Doxycycline Combination for Skin Infections

For typical skin infections, combining Augmentin (amoxicillin-clavulanate) with doxycycline is only appropriate when MRSA coverage is specifically needed alongside polymicrobial or streptococcal coverage; otherwise, monotherapy with Augmentin alone is sufficient and preferred. 1

When Augmentin Monotherapy is Appropriate

Augmentin alone is the recommended first-line treatment for most uncomplicated skin and soft tissue infections without MRSA risk factors. 1, 2

• For mild to moderate skin infections including impetigo, infected eczema, and cellulitis, Augmentin 875/125 mg twice daily provides adequate coverage against methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus pyogenes 1
• Augmentin is specifically recommended as the oral treatment of choice for animal bites, providing single-agent polymicrobial coverage 1, 2
• For diabetic wound infections classified as mild, Augmentin is listed among first-line oral options 1
• Clinical cure rates with Augmentin monotherapy range from 84-96% in mild to severe pyodermas caused by MSSA 3

When to Add Doxycycline to Augmentin

The combination of doxycycline plus a beta-lactam (such as Augmentin) is indicated only when MRSA coverage is required alongside streptococcal coverage. 1, 2

Specific MRSA Risk Factors Requiring Combination Therapy:

• Presence of purulent drainage or exudate from the infection site 2
• Penetrating trauma or injection drug use history 1, 2
• Known MRSA colonization or previous MRSA infection 2
• Cellulitis associated with concurrent evidence of MRSA infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) present 2

Dosing for Combination Therapy:

• Doxycycline 100 mg orally twice daily PLUS Augmentin 875/125 mg twice daily 1, 2
• Duration typically 5-10 days depending on severity and clinical response 1

Critical Clinical Pitfalls

Do not use doxycycline monotherapy for typical cellulitis, as its activity against beta-hemolytic streptococci is unreliable. 1

• A double-blind study demonstrated that adding trimethoprim-sulfamethoxazole (which has similar streptococcal coverage concerns as doxycycline) to cephalexin provided no additional benefit over cephalexin alone in pure cellulitis 1
• In the absence of abscess, ulcer, or purulent drainage, beta-lactam monotherapy (including Augmentin) is recommended over combination therapy 1

MRSA is an unusual cause of typical cellulitis. 1

• A prospective study showed that beta-lactam treatment (cefazolin or oxacillin) was successful in 96% of cellulitis cases, even in centers with high MRSA prevalence for other infection types 1
• Empiric MRSA coverage should be reserved for cases with specific risk factors listed above 1, 2

Alternative Approaches

If clindamycin susceptibility is confirmed and local resistance is <10%, clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA, eliminating the need for combination therapy. 2

• Clindamycin monotherapy avoids the complexity of dual-drug regimens 1
• However, potential for inducible resistance in erythromycin-resistant MRSA strains limits its use 1

For severe infections requiring hospitalization with MRSA concerns, vancomycin 30-60 mg/kg/day IV in divided doses plus piperacillin-tazobactam provides broader coverage than oral combination therapy. 1

Practical Treatment Algorithm

1. Assess for purulent drainage, penetrating trauma, injection drug use, known MRSA colonization, or SIRS 2
2. If none present: Use Augmentin 875/125 mg twice daily alone for 5-10 days 1
3. If MRSA risk factors present: Add doxycycline 100 mg twice daily to Augmentin 1, 2
4. If clindamycin-susceptible and local resistance <10%: Consider clindamycin monotherapy as alternative 2
5. If severe systemic signs or hospitalization required: Switch to IV vancomycin plus piperacillin-tazobactam 1