What is Beta-Lactamase?
Beta-lactamase is a bacterial enzyme that destroys beta-lactam antibiotics (such as penicillins and some cephalosporins) by breaking open their beta-lactam ring structure, rendering these antibiotics ineffective against the bacteria that produce it.
Mechanism and Clinical Significance
Beta-lactamase functions as a resistance mechanism that bacteria use to survive antibiotic treatment. The enzyme specifically targets the beta-lactam ring—the core structural component responsible for the antibacterial activity of penicillins, ampicillin, amoxicillin, and certain cephalosporins 1.
Beta-Lactamase in Moraxella catarrhalis
Prevalence and Types
Clinicians should assume that all isolates of M. catarrhalis are resistant to amoxicillin, ampicillin, piperacillin, and penicillin due to near-universal beta-lactamase production 1.
- 92-100% of M. catarrhalis isolates produce beta-lactamase, making it one of the most consistently resistant respiratory pathogens 1, 2, 3
- Two phenotypically identical beta-lactamase types exist: BRO-1 (most common at 73-93%) and BRO-2 (5-15%) 1, 4, 5
- BRO-1 produces significantly higher enzyme levels than BRO-2, with ampicillin MICs 6.5-fold higher for BRO-1 producers compared to BRO-2 producers 3
Treatment Implications
Both BRO-1 and BRO-2 enzymes are readily inactivated by beta-lactamase inhibitors (such as clavulanic acid), making amoxicillin-clavulanate the preferred first-line therapy 1, 2.
- Amoxicillin-clavulanate achieves 100% susceptibility against M. catarrhalis 2, 4, 3
- Alternative options include enzyme-stable beta-lactams (second/third-generation cephalosporins), macrolides, tetracyclines, and respiratory fluoroquinolones, all maintaining excellent activity 1
- Critical pitfall: Never use amoxicillin, ampicillin, or penicillin monotherapy for M. catarrhalis infections, as >95% of isolates will be resistant 2
Comparison with Other Respiratory Pathogens
- H. influenzae: 30-40% produce beta-lactamase in the United States, significantly lower than M. catarrhalis 1
- Unlike M. catarrhalis, H. influenzae has developed additional resistance mechanisms beyond beta-lactamase, including BLNAR (beta-lactamase-negative ampicillin-resistant) strains due to altered penicillin-binding proteins 1
- Despite almost universal beta-lactamase prevalence in M. catarrhalis, resistance to other antibacterial classes has not developed, unlike the multidrug resistance patterns seen with S. pneumoniae 1
Molecular Characteristics
The BRO beta-lactamase gene encodes a 314 amino acid polypeptide that functions as a lipoprotein anchored to the bacterial membrane, with approximately 10% of enzyme activity found in the membrane compartment 6. The gene's unusually low G+C content (31% versus 41% for the overall M. catarrhalis genome) indicates acquisition through horizontal gene transfer from another species 6, 7.