What are KPC, OXA-48, and MBL?
KPC (Klebsiella pneumoniae carbapenemase), OXA-48 (Oxacillinase-48), and MBL (Metallo-beta-lactamase) are three major classes of carbapenemase enzymes that allow bacteria to destroy carbapenem antibiotics, representing the most critical mechanisms of antibiotic resistance in Enterobacterales worldwide. 1
Classification and Mechanism
These carbapenemases belong to different Ambler molecular classes, each with distinct biochemical properties:
KPC (Class A): Serine-based carbapenemase that remains the most common type globally, accounting for 47.4% of meropenem-resistant Enterobacterales 1
MBL (Class B): Metallo-beta-lactamases including NDM, VIM, and IMP enzymes that require zinc ions for activity, representing 20.6% of carbapenem-resistant isolates 1
OXA-48 (Class D): Oxacillinase-type carbapenemases accounting for approximately 19% of carbapenem resistance 1
Critical Clinical Differences
The most important distinction is that MBLs hydrolyze ALL beta-lactam antibiotics except aztreonam, while KPC and OXA-48 have different hydrolytic profiles that directly impact treatment selection. 1
MBL Unique Characteristics:
- Hydrolyze all beta-lactam classes except monobactams (aztreonam) 1
- Cannot be inhibited by classic serine beta-lactamase inhibitors (avibactam, vaborbactam) 1
- Often co-produced with ESBLs, further complicating treatment 1
KPC Characteristics:
- Inhibited by newer beta-lactamase inhibitors like avibactam and vaborbactam 2, 3
- Stable to hydrolysis by most other beta-lactamases 2
OXA-48 Characteristics:
- Certain OXA-48-like enzymes (non-carbapenemase OXAs) may not confer full carbapenem resistance 3
- Variable activity against different beta-lactams 1
Why Rapid Identification Matters
Knowing the specific carbapenemase type is crucial because each requires completely different treatment strategies, and time to appropriate therapy directly impacts mortality in critically ill patients. 1
- Rapid testing strategies should be implemented to identify specific carbapenemases and guide antibiotic therapy 1
- Blood culture collection to active antibiotic therapy time influences outcomes in KPC-producing bloodstream infections 1
Treatment Implications by Carbapenemase Type
For KPC Producers:
- First-line: Ceftazidime/avibactam or meropenem/vaborbactam (STRONG recommendation, MODERATE evidence) 1
- Vaborbactam specifically protects meropenem from KPC degradation 2
- Avibactam inactivates KPC carbapenemases 3
For OXA-48 Producers:
- First-line: Ceftazidime/avibactam (CONDITIONAL recommendation, VERY LOW evidence) 4
- Avibactam demonstrates activity against certain OXA-48-like enzymes 3
- Local resistance patterns must guide therapy as resistance to ceftazidime/avibactam has been reported 4
For MBL Producers:
- First-line: Ceftazidime/avibactam PLUS aztreonam (STRONG recommendation) 4
- Alternative: Cefiderocol 4
- Neither vaborbactam nor avibactam inhibit MBLs 2, 3
- Aztreonam remains stable against MBLs since they cannot hydrolyze monobactams 1
Geographic Distribution and Epidemiology
- KPC: Most prevalent in the United States, Greece, and Italy with worldwide spread 5
- NDM (MBL type): Widespread in the Indian subcontinent with global dissemination 5
- OXA-48: Predominantly in Mediterranean and southern European countries with rapid spread 5
- Carbapenem resistance has increased more than seven-fold since 2006 in Europe 1
Common Pitfalls to Avoid
- Do not assume all carbapenem-resistant bacteria have the same carbapenemase - treatment efficacy depends entirely on the specific enzyme class 1
- Do not use meropenem/vaborbactam or ceftazidime/avibactam monotherapy for MBL producers - these agents are not active against metallo-beta-lactamases 2, 3
- Do not delay rapid carbapenemase testing - phenotypic susceptibility testing alone is insufficient for optimal treatment selection 1
- Be aware of co-production - bacteria can harbor multiple carbapenemase genes simultaneously (e.g., OXA-48 plus NDM), complicating treatment 6, 7