Table 2:
Spectrum of Activity anti-CRE therapeutics
| Agent | Therapeutic Class | Activity against Class A | Activity against Class B | Activity against Class D | Notes |
|---|---|---|---|---|---|
| Aztreonam | Monobactam | − | + | + | Not recommended. CRE often have co-occurring ESBL enzymes which render aztreonam ineffective. |
| Colistin, Polymyxin B | Polymyxin | +/− | +/− | +/− | Limited efficacy, significant toxicities. |
| Fosfomycin | Phosphoenolpyruvate analogue | + | + | + | Primarily used for urinary tract infections. |
| Tigecycline | Tetracycline | +/− | +/− | +/− | Typically used as combination therapy. |
| Ceftazidime-avibactam | β-lactam-β-lactamase inhibitor | + | − | + | Approved for cUTI, cIAI (with metronidazole), HAP/VAP. Can be used with aztreonam for treatment of NDM-producing infections. |
| Meropenem-vaborbactam | β-lactam-β-lactamase inhibitor | + | − | − | Approved for cUTI, cIAI, HAP/VAP. |
| Imipenem-relebactam | β-lactam-β-lactamase inhibitor | + | − | − | Approved for cUTI, cIAI by FDA. Approved for HAP/VAP, BSI, resistant GN infections by EMA. |
| Plazomicin | Aminoglycoside | + | + | + | NDM-carrying CRE often resistant due to 16s ribosomal methyltransferases. Approved for cUTI by FDA. Not approved by EMA. |
| Eravacycline | Tetracycline | + | + | + | Approved for cIAI by FDA and EMA. |
| Omadacycline | Tetracycline | + | + | + | Oral and IV formulations. Approved by FDA for ABSSSI and CABP. Not approved by EMA. |
| Cefiderocol | Cephalosporin | + | + | + | Approved for cUTI and HAP/VAP by FDA. Approved for resistant GN infections by EMA. CREDIBLE-CR study showed increased all-cause mortality. |
| Phage therapy | N/A | + | + | + | Few clinical trials showing efficacy for CRE at this time. Require specificity for infecting organism, often leading to significant lag time to start treatment. |
| Zidebactam* | β-lactamase inhibitor | + | +/− | + | Combined with cefepime. Clinical trials pending. |
| Taniborbactam* | β-lactamase inhibitor | + | + | + | Combined with cefepime. Currently in phase 3 trials for cUTI. |
| LYS228* | Monobactam | + | + | +/− | No clinical trials currently underway |
| Nacubactam* | β-lactamase inhibitor | + | +/− | + | Combined with meropenem. Completed phase 1 clinical trials. |
cUTI=complicated urinary tract infection; cIAI=complicated intraabdominal infection; HAP/VAP=hospital acquired pneumonia/ventilator-associated pneumonia; GN=gram negative; ABSSSI=acute bacterial skin and skin structure infection; CABP=community acquired bacterial pneumonia; FDA= United States Food and Drug Administration; EMA= European Medicines Agency.
*
antibiotic currently in development