Efficacy data from large, randomised clinical trials investigating the use of novel agents with anti-Gram-negative activity in patients with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP)
| Reference, trial | Drugs (dosage) | Comparators (dosage) | Primary end-point | Disease and study population for the primary analysis | Cured/total (rates, %) | Percent difference (95% CI) |
| Nicholson et al. [19] | Ceftobiprole (500 mg every 8 h for 7–14 days) | Ceftriaxone (2 g every 24 h for 7–14 days) ± linezolid (600 mg every 12 h if MRSA suspected) | Clinical cure rate at the TOC visit | CAP severe enough to require hospitalisation | ||
| ITT population | ||||||
| Ceftobiprole | ITT 240/314 (76.4) | – | ||||
| Ceftriaxone±linezolid | ITT 257/324 (79.3) | |||||
| CE population | ||||||
| Ceftobiprole | CE 200/231 (86.6) | – | ||||
| Ceftriaxone±linezolid | CE 208/238 (87.4) | |||||
| Awad et al. [20] | Ceftobiprole (500 mg every 8 h for 7–14 days) | Ceftazidime (2 g every 8 h) plus linezolid (600 mg every 12 h) for 7–14 days | Clinical cure rate at the TOC visit | HAP including VAP | ||
| ITT population | ||||||
| Ceftobiprole | ITT 195/391 (49.9) | −2.9 (−10.0–4.1) | ||||
| Ceftriaxone plus linezolid | ITT 206/390 (52.8) | |||||
| CE population | ||||||
| Ceftobiprole | CE 174/251 (69.3) | −2.0 (−10.0–6.1) | ||||
| Ceftriaxone plus linezolid | CE 174/244 (71.3) | |||||
| Kollef et al.[34], ASPECT-NP | Ceftolozane-tazobactam (3 g every 8 h for 8–14 days) | Meropenem (1 g every 8 h for 8–14 days) | 28-day all-cause mortality | Ventilated nosocomial pneumonia | ||
| ITT population | ||||||
| Ceftolozane-tazobactam | 87/362 (24.0) | 1.1 (−5.1–7.4) | ||||
| Meropenem | 92/364 (25.3) | |||||
| Torres et al. [48], REPROVE | Ceftazidime-avibactam (2 g/0.5 g every 8 h for 7–14 days) | Meropenem (1 g every 8 h for 7–14 days) | Clinical cure at TOC visit | Nosocomial pneumonia including VAP | ||
| cMITT population | ||||||
| Ceftazidime-avibactam | 245/356 (68.8) | −4.2 (−10.76–2.46) | ||||
| Meropenem | 270/370 (73.0) | |||||
| CE population | ||||||
| Ceftazidime-avibactam | 199/257 (77.4) | −0.7 (−7.9–6.4) | ||||
| Meropenem | 211/270 (77.1) | |||||
| Wunderink et al. [62], APEKS-NP | Cefiderecol (2 g every 8 h for 7–14 days) | Meropenem (2 g every 8 h for 7–4 days) | All-cause 14-day mortality | HAP, VAP or HCAP | ||
| ITT population | ||||||
| Cefiderocol | 18/145 (12.4) | 0.8 (−6.6–8.2) | ||||
| Meropenem | 17/146 (11.6) | |||||
| Bassetti et al. [63], CREDIBLE-CR | Cefiderecol (2 g every 8 h for 7–14 days) | Best available therapy | Clinical cure at TOC | Nosocomial pneumonia | ||
| CR-mITT population | ||||||
| Cefiderocol | 20/40 (50.0) | – | ||||
| Best available therapy | 10/19 (52.6) | |||||
| Wunderink et al.[73], TANGO II | Meropenem-vaborbactam (2 g/2 g every 8 h for 7–14 days) | Best available therapy | Day 28 all-cause mortality | Carbapenem-resistant Enterobacterales HABP/VABP | ||
| mCRE-MITT population | ||||||
| Meropenem-vaborbactam | 4/20 (22.2) | −22.2# | ||||
| Best available therapy | 4/9 (44.4) | |||||
| Motsch et al. [85], STORE IMI-1 | Imipenem-relebactam (500 mg/250 mg every 6 h for 5–21 days) | Imipenem (500 mg every 6 h) plus colistin (loading dose 300 mg then 150 mg every 12 h) | Favourable overall response | HAP/VAP | ||
| mMITT population | ||||||
| Imipenem-relebactam | 7/8 (87.5) | – | ||||
| Imipenem plus colistin | 2/3 (66.6) | |||||
| Titov et al. [86], RESTORE-IMI 2 | Imipenem-relebactam (500 mg/250 mg every 6 h for 7–14 days) | Piperacillin/tazobactam (4 g/0.5 g every 6 h for 7–14 days) | Day 28 all-cause mortality | HABP/VABP | ||
| mITT population | ||||||
| Imipenem-relebactam | 42/264 (15.9) | −5.3 (−11.9–1.2) | ||||
| Piperacillin/tazobactam | 57/267 (21.3) | |||||
| McKinnel et al. [96], CARE | Plazomicin (15 mg·kg−1 every 24 h for 7–14 days) plus meropenem or tigecycline | Colistin 5 mg·kg−1 every 24 h plus meropenem or tigecycline | Composite of death from any cause at 28 days or clinically significant disease-related complications | HAP or VAP caused by suspected or confirmed CRE | ||
| mMITT population | ||||||
| Plazomicin-based regimen | 2/3 (67) | 27 (−48–82) | ||||
| Colistin-based regimen | 2/5 (40) | |||||
CE: clinically evaluable; cMITT: clinically modified intention-to-treat (population); CR: carbapenem resistant; CR-MITT: carbapenem-resistant microbiological ITT (population); HABP: hospital-acquired bacterial pneumonia; HCAP: healthcare-associated pneumonia; ITT: intent-to-treat (population); mCRE-MITT: microbiologic carbapenem resistant Enterobacterales-modified intent-to-treat (population); mITT: modified intent-to-treat (population); mMITT: modified microbiological intent to treat (population); MRSA: methicillin-resistant Staphylococcus aureus; TOC: test of cure; VABP: ventilator-associated bacterial pneumonia. #Data represent the difference in percentages for meropenem-vaborbactam and best available therapy.