What is the best oral antibiotic for a patient with a wound infection?

Best Oral Antibiotic for Wound Infection

For most wound infections requiring oral antibiotics, amoxicillin-clavulanate 875/125 mg twice daily is the first-line choice, providing broad coverage against the most common pathogens including staphylococci, streptococci, and anaerobes. 1, 2, 3

Selection Algorithm Based on Wound Type

Mild Uncomplicated Wound Infections

• First-line: Amoxicillin-clavulanate 875/125 mg PO twice daily for 5-10 days 1, 2, 3
• Alternative if penicillin allergy: Clindamycin 300 mg PO three times daily (covers staphylococci, streptococci, and anaerobes) 1
• For suspected MRSA: TMP-SMX 160-800 mg twice daily OR doxycycline 100 mg twice daily 1, 3

The IDSA guidelines emphasize that for mild to moderate infections in patients without recent antibiotic exposure, therapy targeting aerobic gram-positive cocci is typically sufficient 1. However, amoxicillin-clavulanate provides broader coverage that addresses the polymicrobial nature of most wound infections 1.

Purulent Cellulitis (with drainage but no drainable abscess)

• Empiric coverage for CA-MRSA is mandatory pending culture results 1
• Options include:
  • TMP-SMX 160-800 mg twice daily 1
  • Doxycycline 100 mg twice daily 1
  • Clindamycin 300 mg three times daily (if local resistance <10%) 1
  • Linezolid 600 mg twice daily 1

Nonpurulent Cellulitis (no drainage or abscess)

• Target β-hemolytic streptococci first: Cephalexin 500 mg three times daily 1
• Add MRSA coverage only if: Patient fails β-lactam therapy or has systemic toxicity 1

Bite Wounds (Animal or Human)

Animal bites:

• First-line: Amoxicillin-clavulanate 875/125 mg twice daily 1, 2, 3
• If penicillin allergy: Doxycycline 100 mg twice daily (excellent against Pasteurella multocida) 1
• Alternative: Moxifloxacin 400 mg daily (monotherapy with anaerobic coverage) 1

Human bites:

• First-line: Amoxicillin-clavulanate 875/125 mg twice daily 1, 2, 3
• If penicillin allergy: Doxycycline 100 mg twice daily OR moxifloxacin 400 mg daily 1
• Critical pitfall: Never use first-generation cephalosporins (cephalexin, cefazolin) for human bites—they miss Eikenella corrodens, a key pathogen 1, 3

Diabetic Foot Infections

Mild to moderate (no recent antibiotics):

• Amoxicillin-clavulanate 875/125 mg twice daily 1, 3
• Duration: 1-2 weeks for mild, 2-3 weeks for moderate infections 1

Moderate to severe or recent antibiotic exposure:

• Levofloxacin 750 mg daily OR moxifloxacin 400 mg daily 1, 3
• Consider MRSA coverage if: prior MRSA history, high local prevalence, or severe infection 1

Essential principle: Antibiotics are insufficient without proper wound debridement and care 1. Clinically uninfected wounds should never receive antibiotics 1.

Critical Timing and Duration Principles

• Prophylactic antibiotics: Administer within 60 minutes of presentation for bite injuries 2
• Treatment duration: 5-10 days for most infections, individualized by clinical response 1
• Stop antibiotics when: Infection signs resolve, NOT when wound fully heals 1
• Avoid prolonged courses: Increases resistance risk without additional benefit 2, 3

Essential Non-Antibiotic Measures

These are MORE important than antibiotics:

• Wound irrigation and surgical debridement substantially decrease infection incidence more than antibiotics alone 2
• Deep irrigation removes foreign bodies and pathogens 2
• Avoid high-pressure irrigation—it spreads bacteria into deeper tissues 2

Tetanus prophylaxis:

• Give if >10 years since last dose (clean wounds) or >5 years (dirty wounds) 1, 2
• Tdap preferred over Td if not previously given 1, 2

Critical Pitfalls to Avoid

Antibiotic Selection Errors

• Never close bite wounds primarily (except facial wounds with copious irrigation, debridement, and preemptive antibiotics) 1, 2, 3
• Avoid fluoroquinolones in elderly patients due to tendinopathy, CNS effects, and QT prolongation risks 3
• First-generation cephalosporins miss key pathogens in bite wounds (Pasteurella, Eikenella, anaerobes) 1

Culture and Monitoring

• Obtain cultures before starting antibiotics for established infections 1, 2
• Cultures are mandatory for: severe infections, systemic illness, inadequate response to initial therapy, or concern for outbreak 1
• Deep tissue specimens (biopsy/curettage after debridement) are superior to swabs 1

Special Populations

• Tetracyclines contraindicated in children <8 years old 1
• Fluoroquinolones generally avoided in children <18 years old 1
• Aminoglycosides carry increased nephrotoxicity/ototoxicity risk in elderly patients 3

When to Escalate to IV Therapy

Switch to parenteral antibiotics for:

• Severe infections with systemic toxicity 1
• Failed oral therapy 1
• Inability to tolerate oral medications 1
• Deep tissue involvement requiring broader coverage 1