Why is levofloxacin (a fluoroquinolone antibiotic) being given to a sexually active adult patient with a bacterial skin infection, such as cellulitis or abscess, on the penile shaft?

Levofloxacin for Penile Shaft Bacterial Skin Infection

Levofloxacin is being used because it is FDA-approved for both uncomplicated and complicated skin and skin structure infections, but this represents suboptimal therapy for typical cellulitis in a sexually active adult—you should strongly consider switching to beta-lactam monotherapy unless specific risk factors for MRSA or atypical pathogens are present. 1

Why Levofloxacin Was Likely Chosen

• The FDA explicitly approves levofloxacin for uncomplicated skin and skin structure infections (including cellulitis) caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes at 500 mg once daily for 7-10 days. 1
• Levofloxacin is also FDA-approved for complicated skin and skin structure infections at 750 mg once daily for 7-14 days. 1
• The once-daily dosing and broad-spectrum coverage make it an attractive empiric choice for clinicians unfamiliar with current cellulitis guidelines. 2, 3

Critical Problem: Levofloxacin Is NOT First-Line for Typical Cellulitis

The Infectious Diseases Society of America explicitly states that fluoroquinolones like levofloxacin should be reserved for patients with beta-lactam allergies or specific clinical scenarios, NOT used as routine first-line therapy for cellulitis. 4, 5

• Beta-lactam monotherapy (cephalexin, dicloxacillin, amoxicillin) is the standard of care for typical nonpurulent cellulitis, with a 96% success rate. 5
• Fluoroquinolones are approved for uncomplicated cellulitis but lack adequate MRSA coverage and should be reserved for beta-lactam-allergic patients. 4
• The 2018 World Society of Emergency Surgery guidelines state that fluoroquinolones are "not adequate for treatment of MRSA infections." 4

When Levofloxacin Might Be Appropriate in This Context

Scenario 1: Disseminated Gonococcal Infection (DGI)

• If this sexually active adult has petechial or pustular skin lesions on the penile shaft with asymmetrical arthralgia or tenosynovitis, this could represent DGI rather than simple cellulitis. 4
• The CDC STD Treatment Guidelines list levofloxacin 250 mg IV daily as an alternative regimen for DGI (though ceftriaxone 1 g IM/IV every 24 hours is the recommended first-line). 4
• Critical caveat: Quinolones should NOT be used for infections in men who have sex with men (MSM), those with recent foreign travel, or infections acquired in California, Hawaii, or other areas with increased quinolone-resistant Neisseria gonorrhoeae (QRNG) prevalence. 4
• After 24-48 hours of IV therapy with clinical improvement, levofloxacin 500 mg orally once daily can complete at least 1 week of therapy. 4

Scenario 2: Beta-Lactam Allergy

• If the patient has a documented severe penicillin/cephalosporin allergy, levofloxacin becomes a reasonable alternative for typical cellulitis. 5
• However, clindamycin 300-450 mg orally every 6 hours would still be preferred as it covers both streptococci and MRSA. 5

Scenario 3: Complicated Skin Infection with Gram-Negative Coverage Needed

• If there is penetrating trauma, injection drug use, or concern for polymicrobial infection including Gram-negatives, levofloxacin provides broader coverage than beta-lactams alone. 1, 6
• The FDA label specifically mentions levofloxacin's activity against Proteus mirabilis and Enterococcus faecalis in complicated skin infections. 1

What You Should Do Now

Step 1: Assess for DGI Risk Factors

• Does the patient have systemic symptoms (fever, arthralgia, tenosynovitis)? 4
• Are there petechial or pustular acral skin lesions elsewhere on the body? 4
• Is there minimal genital inflammation despite skin lesions (characteristic of DGI-causing strains)? 4
• If YES to any of these, continue levofloxacin but switch to ceftriaxone 1 g IM/IV every 24 hours as first-line therapy unless the patient is in a high QRNG prevalence area. 4

Step 2: Assess for Typical Cellulitis

• Is this nonpurulent cellulitis (erythema, warmth, tenderness without drainage or abscess)? 5
• Are there no MRSA risk factors (no penetrating trauma, no injection drug use, no purulent drainage, no known MRSA colonization)? 5
• If YES, switch to cephalexin 500 mg orally every 6 hours for 5 days (extending only if no improvement). 5

Step 3: Assess for Purulent Infection or MRSA Risk

• Is there purulent drainage, exudate, or an abscess? 5
• Does the patient have penetrating trauma or injection drug use history? 5
• If YES, switch to clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA). 5
• Alternatively, use trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin 500 mg every 6 hours. 5

Step 4: Verify Treatment Duration

• The Infectious Diseases Society of America recommends 5 days of treatment if clinical improvement occurs, extending only if symptoms have not improved. 5
• Traditional 7-10 day courses are no longer necessary for uncomplicated cases. 5

Common Pitfalls to Avoid

• Do not continue levofloxacin for typical nonpurulent cellulitis without specific indication—this represents overtreatment and promotes fluoroquinolone resistance. 4, 5
• Do not use levofloxacin if the patient is MSM or has recent travel history without first ruling out gonococcal infection and checking local QRNG prevalence. 4
• Do not assume MRSA coverage is needed just because the infection is on the genitals—MRSA is uncommon in typical cellulitis even in high-prevalence settings. 5
• Do not forget to examine for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics. 5

Bottom Line Algorithm

1. If systemic symptoms + skin lesions + sexually active → Consider DGI → Switch to ceftriaxone 1 g IM/IV daily (unless high QRNG area, then continue levofloxacin 250 mg IV daily). 4
2. If nonpurulent cellulitis + no MRSA risk factors → Switch to cephalexin 500 mg every 6 hours for 5 days. 5
3. If purulent drainage or MRSA risk factors → Switch to clindamycin 300-450 mg every 6 hours for 5 days. 5
4. If severe beta-lactam allergy → Continue levofloxacin 500 mg once daily for 5 days (but clindamycin still preferred). 5