Table 1.
(A). Novel antibiotics against P. aeruginosa. (B). Beta-lactamase inhibitors targeting P. aeruginosa.
| (A) Novel antibiotics against P. aeruginosa. | ||||||
| Treatment/Study | Mechanism of Action | Population | Purpose | Phase | Number of Patients | Year, Reference |
| Inhaled fosfomycin/tobramycin (FTI) after aztreonam inhalation solution (AZLI) run-in (NCT00794586) |
Protein synthesis inhibition | Cystic fibrosis patients with P. aeruginosa respiratory tract infections | Efficacy, safety, and ability to maintain forced expiratory volume (FEV1) in 1 s | II | 120 | 2013, [188] |
| Fosfomycin IV (ZTI-01) and oral fosfomycin (NCT02178254) |
Protein synthesis inhibition | Hospital volunteers | Pharmacokinetics, safety | I | 30 | 2016, [190] |
| POL7080 (murepavadin) (NCT02096315) |
Outer membrane protein inhibitor | Non–cystic fibrosis patients with bronchiectasis | Safety, pharmacokinetics, pharmacodynamics | II | 20 | 2017, [191] |
| Murepavadin (NCT02110459) |
Outer membrane protein inhibitor | Healthy volunteers and renal failure patients | Pharmacokinetics, tolerability, safety | I | 32 | 2019, [192] |
| Murepavadin (PRISM-MDR) (NCT03409679) |
Outer membrane protein inhibitor | Ventilated ICU patients | Treating P. aeruginosa VAP | III | 41 | 2019, [193] |
| Murepavadin (PRISM-UDR) (NCT03582007) |
Outer membrane protein inhibitor | Hospital patients | Treating P. aeruginosa hospital-associated pneumonia | III | 2 | 2019, [194] |
| RC01 (NCT03832517) |
LPS binding | Healthy adult volunteers | Pharmacokinetics, tolerability, safety | I | 8 | 2019, [195] |
| Polymyxin B analogue SPR741 (NCT03376529) |
Plasma membrane disruption and/or antibiotic sensitization | Healthy adult volunteers | Pharmacokinetics, tolerability, safety | I | 27 | 2018, [196] |
| Polymyxin B analogue SPR741 (NCT03022175) |
Plasma membrane disruption and/or antibiotic sensitization | Healthy adult volunteers | Pharmacokinetics, tolerability, safety | I | 64 | 2017, [197] |
| Polymyxin B analogue SPR206 (NCT03792308) |
Plasma membrane disruption and/or antibiotic sensitization | Healthy human volunteers | Pharmacokinetics, tolerability, safety | I | 94 | 2020, [198] |
| Polymyxin B analogue SPR206 (NCT03376529) |
Plasma membrane disruption and/or antibiotic sensitization | Healthy human volunteers | Pharmacokinetics, tolerability, safety | I | 27 | 2018, [196] |
| Polymyxin B analogue MRX-8 (NCT04649541) |
Plasma membrane disruption and/or antibiotic sensitization | Healthy human volunteers | Pharmacokinetics, tolerability, safety | I | 116 | 2021, [199] |
| (B) Beta-lactamase inhibitors targeting P. aeruginosa. | ||||||
| Treatment/Study | Mechanism of Action | Population | Purpose | Phase | Number of Patients | Year, Reference |
| Imipenem/relebactam/cilastatin (NCT02452047 RESTORE-IMI 1) |
Beta-lactamase inhibitor | Patients with HABP, VAPB, urinary tract infections, and intra-abdominal infections | Efficacy at treating HABP, VAPB, urinary tract infections, and intra-abdominal infections | III | 31 | 2019, [200,201] |
| Imipenem/relebactam/cilastatin (NCT02493764-RESTORE-IMI 2) |
Beta-lactamase inhibitor | Patients with HABP or VAPB | Efficacy at treating HABP or VAPB | III | 264 | 2021, [202,203] |
| Imipenem/cilastatin/relebactam (NCT05561764) |
Beta-lactamase inhibitor | Patients with HABP and VAPB | Efficacy at treating HABP and VAPB | III | 274 | 2022, [204] |
| Imipenem/relebactam/Cilastatin (NCT03583333) |
Beta-lactamase inhibitor | Patients with CF pneumonia | Efficacy at treating with CF pneumonia | IV | 16 | 2023, [205] |
| Imipenem/cilastatin/XNW4107 (NCT05204563) |
Beta-lactamase inhibitor | Patients with HABP and VAPB | Efficacy at treating patients with HABP and VAPB | III | 450 | 2023, [206] |
| Nacubactam (NCT02134834, NCT02972255, and NCT03182504) |
Beta-lactamase inhibitor | Healthy human volunteers | Pharmacokinetics, tolerability, safety | I | 21 | 2018, [207,208,209] |