Table 3 List of major randomized, controlled clinical trials of systemic antimicrobial agents actually available for treating NP in the last 10 years
From: Update of the treatment of nosocomial pneumonia in the ICU
Author, year, name of the trial | Antimicrobial tested and comparator | Phase, blinded, design | Microorganism | Subject | Primary outcome | Results of primary outcome | Mortality | Comments |
|---|---|---|---|---|---|---|---|---|
Freire, 2010 [76] | Tigecycline (T) Imipenem (I) | III, yes, NI | All pathogens | HAP + VAP | Clinical response in CE and c-mITT populations at TOC | c-mITT: T, 62.7%; I, 67.6% CE: T, 67.9%; I, 78.2% | T, 14.1% I, 12.2% | T was non-inferior to I for c-mITT but not the CE population due to the results in VAP. FDA warning against T use for VAP. |
Rubinstein, 2011, ATTAIN 1 and 2 [60] | Telavancin (Te) Vancomycin (V) | III, yes, NI | Gram-positive | HAP | Clinical response at FU/TOC | AT: Te, 58.9%; V, 59.5% CE: Te, 82.4%; V, 80.7% | Te, 21.5% V, 16.6% | Increases in serum creatinine level were more common in the telavancin group. |
Kollef, 2012 [78] | Doripenem (D), 7 days Imipenem (I), 10 days | IV, yes, NI | All pathogens | VAP | Clinical cure at EOT (day 10) in the MITT | D, 45.6% I, 56.8% | D, 21.5% I, 14.8% | Non-inferiority of a fixed 7-day treatment with D was no achieved FDA warning against D use for VAP. |
Wunderink, 2012, ZEPHIR [79] | Linezolid (L) Vancomycin (V) | IV, yes, NI | Meticillin-resistant Staphylococcus aureus | HAP + VAP | Clinical outcome at EOS in PP patients | L, 57.6% V, 46.5% | L, 15.7% V, 17% | Nephrotoxicity occurred more frequently with V. |
Ramirez, 2013 [80] | Tigecycline low dose (TLD) Tigecycline high dose (THD) Imipenem | II, yes, NI | All pathogens | HAP + VAP | Clinical response at EOT | THD, 85% TLD, 69.6 I, 75% | – | THD could be necessary to treat HAP/VAP. |
Awad, 2014 [81] | Ceftobiprole medocaril (C) Ceftazidime + Linezolid (CAZ/L) | III, yes, NI | All pathogens | HAP + VAP | Clinical cure at the TOC | ITT: C, 49.9%; CAZ/L, 52.8% CE: C, 69.3%; CAZ/L, 71.3% | C, 16.7% CAZ/L, 18% | Non-inferiority of C compared with CAZ/L was not demonstrated in VAP patients. |
Torres, 2018, REPROVE [82] | Ceftazidime/avibactam (CAZ/AVI) Meropenem (M) | III, yes, NI | All pathogens | HAP + VAP | Clinical cure at the TOC | c-mITT: CAZ/AVI, 68.8%; M, 73% CE: CAZ/AVI, 77.4%; M, 78.1% | CAZ/AVI, 8.1% M, 6.8% | CAZ/AVI could be a potential alternative to carbapenems in HAP/VAP patients. |
Kollef 2019, ASPECT-NP [83] | Ceftolozane/tazobactam (CFT-TAZ) Meropenem | III, yes, NI | All pathogens | HAP + VAP, only patients on MV | 28-day all-cause mortality in ITT | CFT-TAZ, 24% M, 25.3% | CFT-TAZ, 24% M, 25.3% | In HAP and in those in whom previous antibacterial therapy was unsuccessful, CFT-TAZ showed lower mortality. |
Cisneros, 2019, Magic-Bullet [84] | Colistin (Co) Meropenen (M) | IV, no, NI | All pathogens | Late VAP | Mortality at 28 days after randomization in mMITT | Co, 23.2% M, 25.3% | Co, 23.2% M, 25.3% | The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group (33:3% vs 18.8%). |