Can a skin infection of the ear be treated with cefazolin 2 g intravenous combined with probenecid and trimethoprim‑sulfamethoxazole double‑strength orally twice daily for full coverage?

Treatment of Ear Skin Infection with Cefazolin and Trimethoprim-Sulfamethoxazole

Your proposed regimen of cefazolin 2 grams IV with probenecid plus trimethoprim-sulfamethoxazole (Sulfatrim DS) twice daily orally provides appropriate coverage for most skin infections of the ear, but the specific combination and route should be tailored to whether the infection is purulent versus non-purulent cellulitis.

Determining the Type of Infection

The first critical step is identifying whether you are treating:

• Purulent infection (abscess, furuncle with drainage/exudate): MRSA is the primary concern 1, 2
• Non-purulent cellulitis (erythema, warmth, swelling without purulent drainage): β-hemolytic streptococci are the primary pathogens 1

For Purulent Infections (Abscess, Furuncle)

Trimethoprim-sulfamethoxazole (TMP-SMX) DS 1-2 tablets twice daily orally alone is the appropriate first-line therapy after incision and drainage if needed 1, 2. The addition of IV cefazolin is unnecessary for outpatient-manageable purulent infections 1.

• TMP-SMX provides excellent MRSA coverage with an A-II recommendation level 1, 2
• Standard duration is 7-10 days, individualized to clinical response 1, 2
• Incision and drainage is the primary intervention; antibiotics are adjunctive 2

The cefazolin component adds no benefit because purulent infections are predominantly staphylococcal, and TMP-SMX already covers both MSSA and MRSA 1, 2.

For Non-Purulent Cellulitis

Cefazolin 2 grams IV with probenecid 1 gram orally once daily is appropriate monotherapy for outpatient management of moderate cellulitis 3, 4.

• This regimen achieves sustained serum concentrations above MIC for S. aureus and β-hemolytic streptococci throughout the 24-hour dosing interval 3, 5
• Clinical success rates of 86-92% have been demonstrated 3, 4
• Adding TMP-SMX provides no additional benefit and is inappropriate because TMP-SMX has poor activity against β-hemolytic streptococci, the primary pathogens in non-purulent cellulitis 1, 2, 6

Critical Pitfall: Do Not Use TMP-SMX Alone for Non-Purulent Cellulitis

TMP-SMX should never be used as monotherapy for non-purulent cellulitis because Group A Streptococcus has intrinsic resistance to sulfonamides 2, 6. If you suspect both streptococcal cellulitis and MRSA (rare scenario), the appropriate combination is TMP-SMX plus a β-lactam such as cephalexin orally, not IV cefazolin 1.

When Your Proposed Combination Makes Sense

Your exact regimen (IV cefazolin + probenecid + oral TMP-SMX) would only be rational in these specific scenarios:

• Complicated infection requiring hospitalization with both purulent and non-purulent components, where IV therapy is mandated but you want dual oral/IV coverage 1
• Transition from inpatient to outpatient care where you are bridging from IV to oral therapy 3

However, for standard outpatient ear skin infections, this combination represents overtreatment and unnecessary polypharmacy.

Practical Algorithm

1. Purulent (abscess, furuncle with drainage): Incision/drainage + TMP-SMX DS 1-2 tablets PO BID × 7-10 days 1, 2
2. Non-purulent cellulitis, outpatient-appropriate: Cefazolin 2g IV + probenecid 1g PO once daily × 7-10 days 3, 4
3. Non-purulent cellulitis, mild: Cephalexin 500mg PO QID × 5-10 days 1
4. Severe/complicated requiring admission: Cefazolin 1g IV Q8H or vancomycin 15-20 mg/kg IV Q8-12H 1

Dosing Specifics for Your Regimen Components

If you proceed with combination therapy despite the above caveats:

• Cefazolin: 2 grams IV once daily 3, 4
• Probenecid: 1 gram orally with each cefazolin dose 3, 5
• TMP-SMX DS: 1-2 tablets (160mg/800mg) orally twice daily 1, 2, 6

Monitoring and Safety

• Probenecid prolongs cefazolin half-life and increases peak concentrations by blocking renal tubular secretion 3, 5
• Monitor for TMP-SMX hypersensitivity reactions, including Stevens-Johnson syndrome (rare but serious) 2, 7
• Ensure adequate hydration to prevent crystalluria with TMP-SMX 1
• Adjust dosing if creatinine clearance <30 mL/min 8