Do Augmentin (amoxicillin/clavulanic acid) and Unasyn (ampicillin/sulbactam) have similar antimicrobial coverage?

Antimicrobial Coverage Comparison: Augmentin vs Unasyn

Augmentin (amoxicillin/clavulanate) and Unasyn (ampicillin/sulbactam) have broadly similar antimicrobial coverage as both are beta-lactam/beta-lactamase inhibitor combinations targeting gram-positive cocci, many gram-negative bacilli, and anaerobes, though Augmentin demonstrates superior activity against certain pathogens including Haemophilus influenzae and achieves approximately 70% susceptibility against key organisms in intra-abdominal infections compared to Unasyn's lower documented efficacy. 1

Mechanism and Spectrum Overview

Both agents combine a penicillin with a beta-lactamase inhibitor to restore activity against beta-lactamase-producing organisms:

• Augmentin pairs amoxicillin with clavulanic acid, a potent beta-lactamase inhibitor that provides progressive inhibition of bacterial beta-lactamases 2
• Unasyn combines ampicillin with sulbactam, which similarly inhibits beta-lactamases while possessing some intrinsic antibacterial activity 3

Gram-Positive Coverage

Both agents provide comparable coverage against gram-positive organisms:

• Penicillinase-producing Staphylococcus aureus strains are covered by both combinations 4
• Streptococcal species including Streptococcus pneumoniae are susceptible to both agents 5
• Both demonstrate efficacy against enterococci in clinical infections 1

Gram-Negative Coverage: Key Differences

Augmentin demonstrates superior activity against several clinically important gram-negative pathogens:

• Beta-lactamase-producing Haemophilus influenzae strains show excellent susceptibility to Augmentin, which has been specifically developed to target this pathogen 5, 4
• Escherichia coli (including amoxicillin-resistant strains) is reliably covered by Augmentin 4
• Klebsiella species typically show good susceptibility to Augmentin 2, 4
• Proteus mirabilis and Proteus vulgaris are usually sensitive to Augmentin 4

Both agents have limitations against certain gram-negative organisms:

• Enterobacter species remain resistant to both combinations due to chromosomal beta-lactamases less susceptible to inhibition 2, 4
• Pseudomonas aeruginosa is resistant to both Augmentin and Unasyn 2, 4
• Serratia marcescens and Proteus morganii typically resist both agents 4

Anaerobic Coverage

Both combinations provide anaerobic coverage, though with some distinctions:

• Augmentin covers Bacteroides fragilis, the predominant anaerobe in intra-abdominal infections 1, 4
• Unasyn also provides anaerobic coverage and is specifically recommended in guidelines for pelvic inflammatory disease where anaerobic organisms are common 1

Clinical Efficacy Data

In intra-abdominal infections, documented susceptibility rates favor Augmentin:

• Augmentin achieves 70% susceptibility against key pathogens in community-acquired intra-abdominal infections 1
• Unasyn is listed as an alternative regimen but lacks specific susceptibility percentages in the same comparative data 1

In urogenital infections, Unasyn demonstrated 95% clinical and bacteriological efficacy in acute pyelonephritis and excellent results in epididymitis, with particular effectiveness against gram-positive flora and E. coli 3

Guideline Recommendations

For pelvic inflammatory disease, both agents appear in treatment algorithms:

• Unasyn (ampicillin/sulbactam 3g IV every 6 hours) plus doxycycline is an established alternative parenteral regimen 1
• Augmentin (amoxicillin/clavulanate) plus doxycycline was effective for outpatient PID but caused significant gastrointestinal side effects 1

For intra-abdominal infections, Augmentin receives preferential positioning:

• Ampicillin/sulbactam is recommended for mild-to-moderate community-acquired infections as a narrow-spectrum option 1
• Both agents are considered appropriate for community-acquired infections, though more costly broad-spectrum agents should be avoided 1

For chronic wound infections, both appear as treatment options:

• Amoxicillin-clavulanate is listed for mild-to-moderate diabetic foot infections 6
• Ampicillin-sulbactam is recommended for moderate-to-severe diabetic wound infections 6

Practical Considerations

Augmentin offers advantages in:

• Respiratory tract infections where H. influenzae coverage is critical 5
• Community-acquired infections requiring oral therapy with high bioavailability 5
• Situations requiring twice-daily dosing for improved compliance 5

Unasyn may be preferred when:

• Parenteral therapy is required for severe infections 1
• Cost considerations favor generic ampicillin-based combinations 1
• Treating urogenital infections where documented efficacy exists 3

Common Pitfalls

• Neither agent provides adequate coverage for hospital-acquired infections with resistant gram-negative organisms including Pseudomonas, Enterobacter, or Serratia 4
• Do not use either agent as monotherapy when Pseudomonas aeruginosa is suspected 4
• Augmentin's gastrointestinal side effects may limit tolerability in some patients, particularly with higher doses 1
• Both agents require dose adjustment in renal impairment to prevent accumulation 5