What antibiotics are used to treat soft tissue infections?

Antibiotic Selection for Soft Tissue Infections

For uncomplicated cellulitis without systemic signs, use an oral agent targeting streptococci such as cephalexin 500 mg every 6 hours or penicillin VK 250-500 mg every 6 hours; for severe infections with systemic toxicity or suspected MRSA, initiate vancomycin 15 mg/kg IV every 12 hours plus piperacillin-tazobactam 3.375-4.5 g IV every 6-8 hours. 1

Mild, Uncomplicated Infections (Outpatient)

For simple cellulitis without purulence or systemic signs:

• First-line oral options: Cephalexin 500 mg every 6 hours, penicillin VK 250-500 mg every 6 hours, or dicloxacillin (targeting streptococci and methicillin-sensitive S. aureus) 1
• Duration: 5 days minimum, extending if no improvement 1
• Penicillin-allergic patients: Clindamycin 300-450 mg four times daily 1

For purulent infections (abscesses, furuncles):

• Incision and drainage is primary treatment 1
• Add antibiotics if: Systemic signs present, multiple lesions, immunocompromised, or failed drainage alone 1
• Oral options covering MRSA: Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily, doxycycline 100 mg twice daily, or clindamycin 300-450 mg four times daily 1

Moderate Infections (May Require Hospitalization)

For cellulitis with systemic signs (fever, tachycardia) but no MRSA risk factors:

• IV options: Cefazolin 1 g every 8 hours IV or nafcillin/oxacillin 2 g every 6 hours IV 1
• Transition to oral: Once clinically improved, switch to cephalexin 500 mg every 6 hours 1

For cellulitis with MRSA risk factors (penetrating trauma, known MRSA colonization, injection drug use, or SIRS):

• Vancomycin 15 mg/kg IV every 12 hours is the empiric choice 1
• Alternatives: Linezolid 600 mg IV/PO every 12 hours or daptomycin 4 mg/kg IV every 24 hours 1, 2

Severe/Life-Threatening Infections

For necrotizing fasciitis or suspected polymicrobial infection:

• Empiric broad-spectrum regimen: Vancomycin 15 mg/kg IV every 12 hours PLUS piperacillin-tazobactam 3.375 g every 6 hours or 4.5 g every 8 hours IV 1
• Alternative combinations: Vancomycin plus a carbapenem (imipenem 500 mg every 6 hours, meropenem 1 g every 8 hours, or ertapenem 1 g every 24 hours) 1
• Another option: Vancomycin plus ceftriaxone 1 g every 24 hours plus metronidazole 500 mg every 8 hours IV 1
• Urgent surgical debridement is mandatory and takes priority over antibiotics 1

For documented Group A streptococcal necrotizing fasciitis:

• Penicillin 2-4 million units IV every 4-6 hours PLUS clindamycin 600-900 mg IV every 6-8 hours 1
• Clindamycin suppresses toxin production and is superior to penicillin alone in animal models 1
• Continue until no further debridement needed and afebrile for 48-72 hours 1

Special Situations

Pyomyositis:

• Empiric: Vancomycin 15 mg/kg IV every 12 hours 1
• Add gram-negative coverage (fluoroquinolone or third-generation cephalosporin) if immunocompromised or open trauma 1
• For MSSA: Switch to cefazolin 1 g every 8 hours or nafcillin 1-2 g every 4-6 hours 1
• Duration: 2-3 weeks total, IV initially then oral once improved 1

Surgical site infections (trunk/extremity):

• Clean sites: Oxacillin/nafcillin 2 g every 6 hours, cefazolin 0.5-1 g every 8 hours, or vancomycin 15 mg/kg every 12 hours if MRSA suspected 1

Surgical site infections (intestinal/GU tract):

• Single-agent: Piperacillin-tazobactam 3.375 g every 6 hours or 4.5 g every 8 hours, or a carbapenem 1
• Combination: Ceftriaxone 1 g every 24 hours plus metronidazole 500 mg every 8 hours 1

Diabetic foot infections:

• Mild: Same as uncomplicated cellulitis—cephalexin or amoxicillin-clavulanate 1
• Moderate-severe: Broad-spectrum coverage with piperacillin-tazobactam or carbapenem, considering MRSA coverage with vancomycin if risk factors present 1

Animal/human bites:

• Amoxicillin-clavulanate 875/125 mg twice daily orally for outpatient treatment 1, 3
• IV: Ampicillin-sulbactam 3 g every 6 hours or piperacillin-tazobactam 1
• Provides coverage for Pasteurella, anaerobes, and oral flora 3

Key Clinical Pitfalls

Common errors to avoid:

• Do not delay antibiotics in necrotizing infections—mortality increases significantly with each hour of delay; start empiric broad-spectrum therapy immediately while arranging surgery 1, 4
• Do not use macrolides (erythromycin, azithromycin) empirically—resistance rates in S. aureus and streptococci are too high in most regions 1, 5
• Do not forget drainage—antibiotics alone are insufficient for abscesses; incision and drainage is the primary treatment 1
• Monitor for linezolid toxicity—thrombocytopenia occurs in 2.4% of patients, particularly with therapy >2 weeks 2
• Adjust for renal function—vancomycin, daptomycin, and beta-lactams require dose adjustment in renal impairment 1

Monitoring and Duration

Treatment duration:

• Uncomplicated cellulitis: 5 days minimum, extend if not improving 1
• Purulent infections: Until resolution, typically 7-10 days 1
• Necrotizing infections: Until no further debridement needed and afebrile 48-72 hours 1
• Pyomyositis: 2-3 weeks total 1

Transition to oral therapy:

• Switch when clinically improved, afebrile, able to tolerate oral intake, and no ongoing bacteremia 1
• Ensure adequate oral bioavailability (linezolid, clindamycin, fluoroquinolones have excellent oral absorption) 1