Table.
Clinically available serine β-lactamase inhibitors and metallo-β-lactamase inhibitors in clinical trials
| Year of FDA approval | Clinical trial phase | β-lactam partner | Formulation | Usage | Inhibitor type | Inhibition mechanism |
Inhibition profile of the inhibitor |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Serine β-lactamases |
Metallo-β-lactamases |
||||||||||||
| Class A (extended-spectrum β-lactamase) | Class A (KPC) | Class C | Class D | Subclass B1 | Subclass B3 | ||||||||
| Clavulanic acid | 1984 | .. | Amoxicillin | Augmentin | Wide* | First generation | Suicide inhibitor, β-lactam analogue | Yes | No | No | No | No | No |
| Sulbactam | 1987 | .. | Ampicillin | Unasyn | Wide† | First generation | Suicide inhibitor, β-lactam analogue | Yes | No | No | No | No | No |
| Tazobactam | 1993 | .. | Piperacillin | Zosyn | Wide‡ | First generation | Suicide inhibitor, β-lactam analogue | Yes | No | No | No | No | No |
| Tazobactam | 2014 | .. | Ceftolozane | Zerbaxa | cIAIs and cUTIs | First generation | Suicide inhibitor, β-lactam analogue | Yes | No | No | No | No | No |
| Avibactam | 2015 | .. | Ceftazidime | Avycaz | cIAIs and cUTIs | Second generation | Reversible inhibitor, DBO type | Yes | Yes | Yes | Yes | No | No |
| Avibactam | .. | Phase 3 (NCT03580044) | Aztreonam | .. | To be determined§ | Second generation | Reversible inhibitor, DBO type | Yes | Yes | Yes | Yes | Yes | Yes |
| Vaborbactam | 2017 | .. | Meropenem | Vabomere | cUTIs | Third generation | β-lactam transition state analogue, boronate type | Yes | Yes | Yes | Yes | No | No |
| Relebactam | 2019 | .. | Imipenem and cilastatin¶ | Recarbrio | cUTIs and cIAIs | Second generation | Reversible inhibitor, DBO type | Yes | Yes | Yes | No | No | No |
| Taniborbactam | .. | Phase 3 (NCT03840148) | Cefepime | .. | cUTIs | Third generation | β-lactam transition state analogue, boronate type | Yes | Yes | Yes | Yes | Yes‖ | No |
| QPX7728 | .. | Phase 1 (NCT04380207) | .. | .. | .. | Third generation | β-lactam transition state analogue, boronate type | Yes | Yes | Yes | Yes | Yes‖ | No |
FDA=US Food and Drug Administration. cIAI=complicated intra-abdominal infection. cUTI=complicated urinary tract infection. DBO=diazabicyclooctanone.
Clavulanic acid is used to treat a wide variety of bacterial infections, among them: lower respiratory tract infections, acute bacterial otitis media, sinusitis, skin and skin structure infections, and cUTIs.
Sulbactam is used to treat a wide variety of bacterial infections, among them: gynaecological infections, bone and joint infections, cIAIs, and skin and skin structure infections.
Tazobactam with piperacillin is used to treat a wide variety of bacterial infections, among them: cIAIs, skin and skin structure infections, gynaecological infections, community-acquired pneumonia, and nosocomial pneumonia.
The phase 3 study will determine the efficacy against cIAIs, nosocomial pneumonia (including hospital-acquired pneumonia and ventilator associated pneumonia), cUTIs, or bloodstream infections due to metallo-β-lactamase-producing Gram-negative bacteria.
Relebactam is in combination with imipenem and cilastatin.
IMP-type metallo-β-lactamases are weakly inhibited.