Examples of Aminopenicillin Plus Beta-Lactamase Inhibitor Combinations
Besides amoxicillin-clavulanic acid (Augmentin), other examples of aminopenicillin plus beta-lactamase inhibitor combinations include ampicillin-sulbactam and ticarcillin-clavulanate.
Common Aminopenicillin-Beta-Lactamase Inhibitor Combinations
Established Combinations
- Amoxicillin-clavulanic acid (Augmentin): The most widely recognized combination, available in various formulations including standard and high-dose options 1, 2
- Ampicillin-sulbactam: An injectable combination used primarily for moderate to severe infections 1
- Ticarcillin-clavulanate: A broader spectrum combination with activity against Pseudomonas aeruginosa 1, 3
Mechanism of Action
- Beta-lactamase inhibitors (clavulanate, sulbactam, tazobactam) bind to bacterial beta-lactamases, preventing them from inactivating the aminopenicillin component 4, 5
- This preserves the activity of the aminopenicillin against beta-lactamase-producing organisms that would otherwise be resistant 3, 6
Clinical Applications
Respiratory Infections
- Aminopenicillin-beta-lactamase inhibitor combinations are recommended for acute bacterial rhinosinusitis, particularly when beta-lactamase-producing organisms are suspected 1
- High-dose amoxicillin-clavulanate (90 mg/6.4 mg per kg per day) is recommended for children with moderate disease or those who have received antibiotics in the previous 4-6 weeks 1
Skin and Soft Tissue Infections
- For diabetic foot infections, guidelines recommend beta-lactam-beta-lactamase inhibitor combinations such as amoxicillin-clavulanate and ampicillin-sulbactam for mild infections with recent antibiotic exposure 1
- For moderate to severe infections, ticarcillin-clavulanate and piperacillin-tazobactam are recommended options 1
Urinary Tract Infections
- Aminopenicillin-beta-lactamase inhibitor combinations have shown approximately 70% success rates in treating urinary tract infections caused by amoxicillin-resistant organisms 7
- These combinations are particularly valuable for treating complicated UTIs where beta-lactamase-producing organisms are common 5, 6
Pharmacological Considerations
Spectrum of Activity
- Amoxicillin-clavulanate and ampicillin-sulbactam have similar coverage against gram-positive organisms and many Enterobacteriaceae 1, 2
- Ticarcillin-clavulanate has broader gram-negative coverage including Pseudomonas aeruginosa 3
- All combinations are effective against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis 2
Resistance Concerns
- Beta-lactamase inhibitors may induce expression of chromosomal cephalosporinases in some gram-negative bacteria, potentially limiting efficacy 3
- Piperacillin-tazobactam generally has less potential for this antagonistic effect compared to ticarcillin-clavulanate 3
Important Clinical Considerations
Dosing Strategies
- Standard-dose amoxicillin-clavulanate (40/10 mg/kg/day) is typically administered in three divided doses 2
- High-dose formulations (90/6.4 mg/kg/day) are administered in two divided doses and are particularly useful for infections with penicillin-intermediate or resistant S. pneumoniae 2
Adverse Effects
- Gastrointestinal disturbances (diarrhea, nausea, vomiting) are the most common side effects of aminopenicillin-beta-lactamase inhibitor combinations 5, 6
- Twice-daily dosing regimens generally have lower rates of diarrhea compared to three-times-daily regimens 2
Special Considerations
- For anthrax exposure, amoxicillin-clavulanate may not be clinically effective where large numbers of organisms are present, despite its in vitro activity against beta-lactamase-producing strains 1
- For tuberculosis treatment, amoxicillin-clavulanate is not recommended except when providing clavulanate for co-administration with carbapenems 1