Carbapenem Classification and Characteristics
Carbapenems are broad-spectrum beta-lactam antibiotics with an exceptionally wide antimicrobial spectrum, covering gram-positive, gram-negative, and anaerobic pathogens. 1
Structural and Mechanistic Properties
Carbapenems are structurally characterized by a beta-lactam ring with a carbon substitution instead of sulfur in the 4-position of the thiazolidine moiety, distinguishing them from other beta-lactam classes. 2, 3
- These antibiotics function by inhibiting bacterial cell wall synthesis through binding and inactivating penicillin-binding proteins (PBPs), the same mechanism shared by all beta-lactam agents 4
- Carbapenems demonstrate remarkable stability against most beta-lactamases, including AmpC beta-lactamases and extended-spectrum beta-lactamases (ESBLs), which sets them apart from other beta-lactam classes 4, 3
Antimicrobial Spectrum
Carbapenems offer wide-spectrum antimicrobial activity against gram-positive and gram-negative aerobic and anaerobic pathogens, with the notable exception of multidrug-resistant gram-positive cocci. 1
Group 1 Carbapenems (Ertapenem)
- Ertapenem has activity against ESBL-producing pathogens but lacks activity against Pseudomonas aeruginosa and Enterococcus species 1
- The unique spectrum and 4-hour half-life make ertapenem suitable for once-daily administration and more appropriate for community-acquired infections rather than nosocomial infections 4, 5
Group 2 Carbapenems (Imipenem/Cilastatin, Meropenem, Doripenem)
- These agents share activity against non-fermentative gram-negative bacilli, including P. aeruginosa 1
- Imipenem requires co-administration with cilastatin (a dehydropeptidase-1 inhibitor) because it is degraded by renal tubular enzymes, whereas meropenem and doripenem are stable to this enzyme and do not require co-administration 4, 3
- These carbapenems have elimination half-lives of approximately 1 hour, requiring multiple daily doses 4, 6
Clinical Resistance Patterns
For more than two decades, carbapenems have been considered the agents of choice for multidrug-resistant infections caused by Enterobacteriaceae, though carbapenem-resistant organisms are now a critical global concern. 1
Important Resistance Mechanisms
- Resistance develops through structural changes in PBPs, acquisition of metallo-beta-lactamases (Class B enzymes) capable of rapidly degrading carbapenems, or changes in membrane permeability from loss of outer membrane porins 4, 3
- KPC (Class A serine carbapenemase) remains the most common carbapenemase globally, accounting for 47.4% of meropenem-resistant Enterobacterales in the United States 7, 8
- Metallo-beta-lactamases (MBLs including NDM, VIM, IMP) represent approximately 20.6% of carbapenem-resistant isolates and are particularly concerning because they hydrolyze all beta-lactams except aztreonam and cannot be inhibited by classic serine beta-lactamase inhibitors 7, 8, 9
Stewardship Considerations
The use of carbapenems should be limited to preserve activity of this antibiotic class because of the concern for emerging carbapenem-resistance. 1
- Carbapenem-sparing strategies using beta-lactam/beta-lactamase inhibitor combinations are desirable in settings where resistance is prevalent 1
- Novel beta-lactams with anti-carbapenemase activity (ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam) should be reserved for patients colonized with carbapenem-resistant Enterobacterales or when rapid molecular testing identifies specific genetic determinants 1
Pharmacodynamic Properties
As time-dependent antibiotics, the most important pharmacodynamic parameter predicting carbapenem efficacy is the time that plasma drug concentration remains above the minimum inhibitory concentration (T>MIC). 4, 6