Table 1.
Clinical trials in complicated urinary tract infection (cUTI).
| First Author (Ref) | Resistant Microorganisms ǂ | Dose New Antibiotic (n Patient) | Comparator, Dose (n Patient) | Definition Outcome | Timing Assessment of Outcomes | Outcomes (New Antibiotics vs. Comparator) |
|---|---|---|---|---|---|---|
| Plazomicin | ||||||
| Wagenlehner [18] | ESBL 26.5% CRE 4.8% |
15 mg/kg IV, QD (n = 306) | Meropenem 1 g IV, TID (n = 303) | Clinical cure and microbiological response | 15 to 19 days after start of therapy | 81.7% vs. 70.1% |
| Conolly [19] | Ceftazidime non-susceptible 17.6% | 15 mg/kg IV, QD (n = 51) | Levofloxacin 750 mg IV, QD (n = 29) | Microbiological eradication rate | 12 days after the last dose | 60.8% vs. 58.6% |
| Eravacycline | ||||||
| Clinical trial identifier NCT03032510 | No information | 1.5 mg/kg IV, QD + levofloxacin PO (n = 603). | Ertapenem 1 g IV, QD + levofloxacin PO (n = 602). | Clinical cure and microbiological response | 14 to 17 days post randomization | 84.8% vs. 94.8% |
| Clinical trial identifier NCT01978938 | No information | 1.5 mg/kg IV, QD (n = 455). | Levofloxacin 750 mg IV, QD (n = 453). | Clinical cure and microbiological response | Post-treatment visit | 60.4% vs. 66.9% |
| Cefiderocol | ||||||
| Portsmouth [21] | No information | 2 g IV, TID (n = 252) | Imipenem-cilastatin 1 g IV, TID (n = 119) |
Clinical cure and microbiological response | 7 ± 2 days after end of antibiotic treatment | 73%, vs. 55% |
| Ceftazidime/avibactam | ||||||
| Carmeli [22] a | Ceftazidime non-susceptible Enterobacterales or P. aeruginosa 100% | 2 g/500 mg IV, TD (n = 165) | Best available therapy (97% carbapenems) (n = 168) | Clinical response | 7 to 10 days after last infusion | 91% vs. 91% |
| Wagenlehner [23] | Ceftazidime non-susceptible 19.6% | 2 g/500 mg IV, TD (n = 393) | Doripenem 500 mg IV, TD (n = 417) | Clinical cure and microbiological response | 21 to 25 days post-randomization | 71.2% vs. 64.5% |
| Ceftolozane/tazobactam | ||||||
| Popejoy [24] | ESBL 11.1% | 1 g/500 mg IV, TD (n = 54) | Levofloxacine 750 mg IV, QD (n = 46) Meropenem 1 g, IV, TD (n = 26) |
Clinical cure | 5 to 9 days post therapy | 95.8% vs. 82.6% (p = 0.01) |
| Wagenlehner [25] | ESBL 14.8% | 1 g/500 mg IV, TD (n = 398) | Levofloxacine 750 mg IV, QD (n = 402) | Clinical cure and microbiological response | 5 to 9 days post therapy | 76.9% vs. 68.4% |
| Meropenem/vaborbactam | ||||||
| Kaye [26] | Piperacillin/tazobactam-resistant E. coli and K. pneumoniae 15% | 2 g/2 g IV, TD (n = 274) | Piperacillin/tazobactam 4 g/500 mg IV, TD (n = 276) | Clinical cure and microbiological response | End of intravenous treatment | 98.4% vs. 94.0% |
| Wunderink [27] b | Multicenter study (27 CRE 78.7% | 2 g/2 g IV, TD (n = 32) | Best available therapy (n = 15) (46.7% dual therapy) | Cure rates | At day 28 | 65.6% vs. 33.3% (95%CI: 3.3. to 61.3) |
| Imipenem+ cilastatin/relebactam | ||||||
| Motsch [28] c | Imipenem-nonsusceptible microorganisms 100% | 500 mg/250 mg IV, QD (n = 31) | Colistimethate Sodium + imipenem + cilastatin loading dose 300 mg colistin base activity, followed by maintenance doses up to 150 mg colistin base activity, IV, BD (n = 16) | Clinical and microbiological response Survival (HAP/VAP) Clinical response (cIAI) |
On therapy visit (cUTI) At day 28 (HAP/VAP and cIAI) |
71.4% vs.70.0% Favorable overall response against P. aeruginosa: 81% vs. 63% |
Abbreviations: IV, intravenous; PO, by mouth; BD, twice daily; TID, three times daily; QD, once a day; ESBL, extended-spectrum beta-lactamases, CRE, carbapenem-resistant Enterobacterales; cUTI, complicated urinary tract infection; cIAI, complicated intra-abdominal infection; HAP/VAP, hospital-acquired pneumonia/ventilator-associated pneumonia. ǂ Only data on ESBL or CRE are mentioned; if total data not available, only data from new antibiotics are included; a also included patients with complicated intra-abdominal infection (<10%); b 34% cUTI patients, also included 10.6% patients with HAP/VAP and 46.8% bacteremia; c 51.6% cUTI, also included 35.5% patients with HAP/VAP, and 12.9% cIAI.