Antimicrobial Coverage Comparison: Augmentin vs Unasyn
Augmentin (amoxicillin/clavulanate) and Unasyn (ampicillin/sulbactam) have overlapping but not identical coverage, with Augmentin offering broader gram-negative and anaerobic activity, while Unasyn is primarily reserved for parenteral therapy in hospitalized patients with similar but slightly narrower spectrum. 1, 2
Spectrum of Activity: Key Similarities
Both agents are beta-lactam/beta-lactamase inhibitor combinations that cover:
- Beta-lactamase-producing Staphylococcus aureus (MSSA only, not MRSA) 1, 2
- Beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis 1, 3
- Beta-lactamase-producing Escherichia coli and Klebsiella species 1, 2
- Anaerobes including Bacteroides fragilis 2, 4
Critical Differences in Coverage
Gram-Negative Coverage
- Augmentin has broader gram-negative activity, including better coverage of Enterobacteriaceae and beta-lactamase-producing strains 5, 1
- Unasyn covers additional organisms like Proteus mirabilis, Enterobacter species, and Acinetobacter calcoaceticus that are specifically listed in its FDA indication 2
Anaerobic Coverage
- Both cover Bacteroides fragilis, though approximately 30% resistance exists for both agents 5
- Augmentin provides excellent anaerobic coverage with approximately 70% susceptibility for B. fragilis 5
Route of Administration
- Augmentin is oral only 1
- Unasyn is intravenous only 2
- This fundamental difference dictates their clinical use: Augmentin for outpatient/oral therapy, Unasyn for hospitalized patients requiring parenteral treatment
Clinical Application Algorithm
When to Choose Augmentin:
- Outpatient respiratory tract infections (sinusitis, otitis media, lower respiratory tract infections) caused by beta-lactamase-producing H. influenzae or M. catarrhalis 6, 1
- Mild-to-moderate community-acquired intra-abdominal infections requiring single-agent oral therapy with anaerobic coverage 5
- Skin and soft tissue infections in outpatient settings caused by beta-lactamase-producing S. aureus, E. coli, or Klebsiella 1
- Diabetic foot infections (moderate severity) where gram-negative and anaerobic coverage is needed 5
When to Choose Unasyn:
- Hospitalized patients requiring parenteral therapy for skin/soft tissue infections, intra-abdominal infections, or gynecological infections 2
- Polymicrobial infections involving beta-lactamase-producing organisms where IV therapy is necessary 2
- Infections caused by Acinetobacter calcoaceticus, which is specifically covered by Unasyn but not emphasized in Augmentin's spectrum 2
Important Clinical Pitfalls
Resistance Considerations:
- Review local E. coli resistance patterns before using either agent, as resistance to both is increasing 5, 7
- B. fragilis resistance is approximately 30% for both agents, requiring alternative therapy if suspected 5
- Neither agent covers Pseudomonas aeruginosa, MRSA, or VRE 5, 2
Enterococcal Coverage:
- Both have limited enterococcal activity, only against ampicillin-susceptible strains 5
- Do not rely on either agent for empiric enterococcal coverage in nosocomial infections
Drug-Induced Liver Injury:
- Augmentin carries higher risk of drug-induced liver injury (DILI) compared to other beta-lactams 5
- Monitor liver function in patients on prolonged therapy
High-Dose Formulations:
- High-dose Augmentin (90 mg/kg/day in children; 4g/day in adults) is required for drug-resistant Streptococcus pneumoniae 6, 3
- Standard dosing may be inadequate for respiratory pathogens with elevated MICs 6
When Neither Agent is Appropriate
- Nosocomial postoperative infections require broader coverage against Pseudomonas, Enterobacter, MRSA, and enterococci—neither Augmentin nor Unasyn is adequate 7
- High-severity intra-abdominal infections require third/fourth-generation cephalosporins plus metronidazole, or carbapenems 7
- Infections with documented ampicillin-susceptible organisms should use amoxicillin or ampicillin alone to avoid unnecessary beta-lactamase inhibitor exposure 1, 2