What is the most appropriate antibiotic for a patient with a skin infection: Augmentin (amoxicillin/clavulanate), cefuroxime, or clindamycin?

Antibiotic Selection for Skin Infections

For uncomplicated skin infections without MRSA risk factors, Augmentin (amoxicillin-clavulanate) is the preferred choice among these three options, offering superior coverage against both Staphylococcus aureus (including penicillinase-producing strains) and Streptococcus pyogenes. 1

Treatment Algorithm Based on Infection Type

For Mild, Uncomplicated Skin Infections (Impetigo, Simple Cellulitis)

• First choice: Augmentin (amoxicillin-clavulanate) provides optimal coverage for the most common pathogens in skin infections, including penicillinase-resistant staphylococci and streptococci 1, 2
• Augmentin demonstrated 94% response rates in primary skin sepsis, infected eczema, and infected trauma, particularly effective against amoxicillin-resistant Staphylococcus aureus 2
• Clindamycin is the preferred alternative if the patient has beta-lactam allergy or intolerance 1
• Cefuroxime can be used but offers no advantage over Augmentin and has narrower anaerobic coverage 1

For Moderate to Severe Skin Infections

• Augmentin remains first-line for infections requiring oral therapy with broader coverage 1
• The IDSA guidelines specifically list amoxicillin-clavulanic acid for purulent skin infections most likely due to Staphylococcus aureus 1
• Cefuroxime (second-generation cephalosporin) is acceptable for moderate-severe infections when combined with metronidazole for anaerobic coverage 1
• Clindamycin provides excellent coverage and has the added benefit of suppressing toxin production in severe infections 1, 3

For MRSA or High-Risk Infections

• Clindamycin becomes the preferred choice among these three options for suspected or confirmed MRSA 1, 4
• The IDSA specifically recommends clindamycin for MRSA skin infections 1
• A head-to-head trial showed clindamycin achieved 80.3% cure rates versus 77.7% for TMP-SMX in uncomplicated skin infections, with no significant difference 4
• Neither Augmentin nor cefuroxime provide adequate MRSA coverage 1

Comparative Strengths and Limitations

Augmentin (Amoxicillin-Clavulanate)

• Broadest spectrum against typical skin pathogens including penicillinase-producing S. aureus, S. pyogenes, and anaerobes 1, 2, 3
• Effective in 94% of mixed infections with penicillin-resistant staphylococci and streptococci 2
• Critical limitation: Requires proper storage; degrades rapidly in hot climates, leading to treatment failure 5
• Side effects limited to nausea (9%), diarrhea (9%), and rash (3%) 2

Cefuroxime

• FDA-approved for skin and skin-structure infections caused by S. aureus (penicillinase and non-penicillinase-producing), S. pyogenes, E. coli, Klebsiella, and Enterobacter 6
• Less optimal than Augmentin because it lacks the beta-lactamase inhibitor, making it less effective against resistant staphylococci 1
• No significant difference in treatment effect between penicillins and cephalosporins for cellulitis (RR 0.99; 95% CI 0.68-1.43) 1
• Reasonable option when Augmentin is unavailable or contraindicated 1

Clindamycin

• Best choice for MRSA coverage among these three options 1, 4
• Suppresses bacterial toxin production, particularly valuable in toxin-mediated syndromes and necrotizing infections 1, 3
• Equivalent efficacy to TMP-SMX for uncomplicated skin infections (89.5% vs 88.2% cure rates) 4
• Important caveat: Higher risk of Clostridioides difficile infection compared to beta-lactams 7
• Should not be used as monotherapy if anaerobic coverage beyond typical skin flora is needed 1, 3

Common Pitfalls to Avoid

• Do not use cefuroxime alone for polymicrobial infections involving anaerobes; add metronidazole or clindamycin 1
• Avoid Augmentin in hot climates without proper storage counseling; heat degradation causes treatment failure 5
• Do not prescribe clindamycin empirically without considering local resistance patterns; macrolide resistance can reach 18.3% in some regions, with cross-resistance to clindamycin 1
• Never use cefuroxime for suspected MRSA infections; it lacks activity against methicillin-resistant strains 1
• Ensure adequate duration: 7-10 days is standard, though no evidence supports 10 days over 7 days for most uncomplicated infections 8

Special Populations

Pediatric Patients

• Augmentin remains first-line with dosing of 25-50 mg/kg/day divided into 3-4 doses 7
• Clindamycin dosing: 10-20 mg/kg/day in 3 divided doses 7
• Cefuroxime is acceptable but offers no advantage over Augmentin in children 8, 3

Penicillin-Allergic Patients

• Clindamycin is the preferred alternative among these options 1, 7
• Cefuroxime can be used cautiously in non-severe penicillin allergy but avoid in immediate-type hypersensitivity 7