Oral Alternatives to Unasyn (Ampicillin-Sulbactam)
The best oral alternative to Unasyn is amoxicillin-clavulanate 875 mg PO every 12 hours, which provides equivalent antimicrobial coverage against the same spectrum of organisms including beta-lactamase producing bacteria. 1
Primary Oral Alternative
Amoxicillin-clavulanate (Augmentin) 875 mg PO every 12 hours is the direct oral equivalent to ampicillin-sulbactam, combining a penicillin with a beta-lactamase inhibitor to provide coverage against Gram-positive, Gram-negative, and anaerobic bacteria 1
This combination maintains activity against beta-lactamase producing organisms that would otherwise be resistant to ampicillin or amoxicillin alone 2, 3
For patients requiring anaerobic coverage (aspiration risk, nursing home residents, intra-abdominal infections), amoxicillin-clavulanate is specifically recommended over other beta-lactams 1
Alternative Dosing Option
Ampicillin-sulbactam oral formulation (sultamicillin) exists as a mutual prodrug that can be given orally, though availability varies by region 2
Sultamicillin has proven effective in clinical trials for respiratory tract infections, urinary tract infections, diabetic foot infections, and skin/soft tissue infections 2
Second-Line Oral Alternatives
For Respiratory Infections
Respiratory fluoroquinolones (levofloxacin 750 mg PO daily or moxifloxacin 400 mg PO daily) provide broader coverage but should be reserved for patients with recent beta-lactam exposure or penicillin allergy 1
Fluoroquinolones should be used cautiously when tuberculosis cannot be excluded, as monotherapy may delay TB diagnosis and promote resistance 1
For Urogenital Infections
Fluoroquinolones (ciprofloxacin 500 mg PO every 12 hours, levofloxacin 500 mg PO daily, or ofloxacin 400 mg PO every 12 hours) are appropriate alternatives for urological procedures and infections 1
Trimethoprim-sulfamethoxazole (1 double-strength tablet PO every 12 hours) can be used for urinary tract infections 1
For Specific Infection Types
First-generation cephalosporins (cephalexin 500 mg PO every 6 hours, cefadroxil 500 mg PO every 12 hours) provide coverage for Gram-positive organisms but lack anaerobic coverage 1
Second-generation cephalosporins (cefuroxime 500 mg PO every 12 hours, cefaclor 500 mg PO every 8 hours) offer broader coverage but still inferior anaerobic activity compared to amoxicillin-clavulanate 1
Critical Considerations
Never use ampicillin alone as an oral alternative when H. influenzae coverage is needed, as it lacks adequate activity against this organism 1
For patients with penicillin allergy, consider respiratory fluoroquinolones or the combination of a cephalosporin plus a macrolide (azithromycin 500 mg PO daily or clarithromycin 500 mg PO every 12 hours) 1
Macrolide monotherapy should never be used in HIV-infected patients or those receiving macrolides for MAC prophylaxis due to resistance concerns 1
Dosing Duration
Most community-acquired infections require 5-7 days of oral therapy 1
Streptococcal pharyngitis/tonsillitis requires at least 10 days of treatment 4
Azithromycin can be given for 3-5 days due to its prolonged tissue half-life 1
Common Pitfall
The most common error is substituting oral cephalosporins without considering the need for anaerobic coverage—amoxicillin-clavulanate remains superior when anaerobic bacteria are suspected (aspiration, intra-abdominal infections, diabetic foot infections) 1, 2, 3.