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Table listing currently used antibiotics for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) and the recommended and approved indications for their use_ Own graphic design based on Paul et al_, (2022)_
| ESBLs | CRE non-CP | CRE-KPC | CRE-O-XA-48 | CRE-MBL | Current clinical indications | Approval | |
|---|---|---|---|---|---|---|---|
| New antibiotics | |||||||
| Cefiderocol | Yes | Yes | Yes | Yes | Yes | cUTIs, HAP, VAP | FDA |
| for the treatment of infectious due to aerobic Gram-negative organisms in adults with limited treatment options | EMA | ||||||
| Ceftolozane-tazobactam | Yes | No | No | No | No | cIAI, cUTIs, HAP, VAP | FDA and EMA |
| Ceftazidime-avibactam | Yes | +/− | Yes | Yes | No | cIAI, cUTIs, HAP, VAP | FDA and EMA |
| for the treatment Gram-negative infections in patients with limited treatment options | EMA | ||||||
| Eravacycline | Yes | Yes | Yes | Yes | Yes | cIAI | FDA and EMA |
| Imipenem-cilastatin-relebactam | Yes | +/− | Yes | No | No | cIAI, cUTIs | FDA |
| HAP, VAP, BSI with a suspected respiratory source, and for the treatment Gram-negative infections in patients with limited treatment options | EMA | ||||||
| Meropenem-vaborbactam | Yes | +/− | Yes | No | No | cUTIs | FDA |
| cUTIs, HAP, VAP, and for the treatment Gram-negative infections in patients with limited treatment options | EMA | ||||||
| Plazomicin | Yes | Yes | Yes | Yes | +/− | cUTIs | FDA |
| EMA application withdrawn | |||||||
| Old antibiotics | |||||||
| Aminoglycosides | +/− | +/− | +/− | +/− | +/− | for the treatment of a variety of bacterial infections | FDA and EMA |
| Aztreonam | No | No | No | No | +/− | for the treatment of infections caused by susceptible Gram-negative micro-organisms | FDA and EMA |
| Fosfomycin iv | Yes | +/− | +/− | +/− | +/− | to treat serious infections when other antibiotics treatment are not suitable | EMA |
| FDA under review | |||||||
| Polymyxins | Yes | Yes | Yes | Yes | Yes | to treat serious infections caused by susceptible strains, when less potentially toxic drugs are ineffective or contraindicated | FDA |
| to treatment of serious infections due to aerobic Gram-negative pathogens in patients with limited treatment options | EMA | ||||||
| Tygecycline | Yes | Yes | Yes | Yes | Yes | complicated SSTI and IAI | FDA and EMA |
| CAP | FDA | ||||||
Classification of preferred substrates for beta-lactam antibiotics, beta-lactamase inhibitors (BLIs), and bacterial beta-lactamases_ Own graphic design based on (Livermore 1995; Bush and Jacoby 2010; Mączyńska 2015; Bush 2018)_
| Molecular class according to Ambler | Bush-Jacoby-Mederios functional group | Preferred substrates in the group of beta-lactam antibiotics | Inhibited by beta-lactamase inhibitors (BLIs): | Bacterial beta-lactamases - representative enzymes | ||
|---|---|---|---|---|---|---|
| AV | CA or TZB | EDTA | ||||
| A | 2a | P | + | + | − | PC1 |
| 2b | P, Cp | + | + | − | TEM-1, TEM-2, SHV-1 | |
| 2be | P, Cp, E, Mb | + | + | − | ESBL (e.g. CTX-M), TEM, SHV, K1 (OXY) in K. oxytoca | |
| 2br | P | + | − | − | TEM-30, SHV-10 | |
| 2c | P, Cbp | + | ± | − | CARB-1, PSE-1, PSE-3, PSE-4 | |
| 2e | Cp | + | + | − | Inducible cephalosporinases Proteus vulgaris | |
| 2f | P, Cp, Cb, E, Mb | + | ± | − | KPC | |
| B | 3a | P, Cp, E, Cb | + | − | + | IMP-1, VIM-1, NDM-1, L1 |
| 3b | Cb | − | − | + | CphA | |
| C | 1 | Cp | + | − | − | AmpC (e.g. MIR-1), CMY |
| 1e | Cp, E | + | − | − | GC1 | |
| D | 2d | P, Clox | + | ± | − | OXA-1, OXA-10 (PSE-2) |
| 2de | P, Cb | + | − | − | OXA-23, OXA-48 | |
| 2df | P, E, Mb | + | ± | − | OXA-11, OXA-15 | |