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Evaluation of Renal Safety Between Imipenem/Relebactam and Colistin Plus Imipenem in Patients With
Michelle L Brown1, Johann Motsch2, Keith S Kaye3
1Merck & Co., Inc., Kenilworth, New Jersey, USA.
Background:
In the randomized controlled RESTORE-IMI 1 clinical trial (NCT02452047), imipenem/cilastatin (IMI) with relebactam (IMI/REL) was as effective as colistin plus IMI for the treatment of imipenem-nonsusceptible gram-negative infections. Differences in nephrotoxicity were observed between treatment arms. As there is no standard definition of nephrotoxicity used in clinical trials, we conducted analyses to further understand the renal safety profile of both treatments.
Methods:
Nephrotoxicity was retrospectively evaluated using 2 acute kidney injury assessment criteria (Kidney Disease Improving Global Outcomes [KDIGO] and Risk, Injury, Failure, Loss, and End-stage Kidney Disease [RIFLE]). Additional outcomes included time to onset of protocol-defined nephrotoxicity and incidence of renal adverse events.
Results:
Of 47 participants receiving treatment, 45 had sufficient data to assess nephrotoxicity (IMI/REL, n = 29; colistin plus IMI, n = 16). By KDIGO criteria, no participants in the IMI/REL but 31.3% in the colistin plus IMI group experienced stage 3 acute kidney injury. No IMI/REL-treated participants experienced renal failure by RIFLE criteria, vs 25.0% for colistin plus IMI. Overall, the time to onset of nephrotoxicity varied considerably (2-22 days). Fewer renal adverse events (12.9% vs 37.5%), including discontinuations due to drug-related renal adverse events (0% vs 12.5%), were observed in the IMI/REL group compared with the colistin plus IMI group, respectively.
Conclusions:
Our analyses confirm the findings of a preplanned end point and provide further evidence that IMI/REL had a more favorable renal safety profile than colistin-based therapy in patients with serious, imipenem-nonsusceptible gram-negative bacterial infections.
Clinicaltrialsgov Identifier:
NCT02452047.
Insights
Imipenem/cilastatin with relebactam (IMI/REL) showed better kidney safety than colistin plus imipenem for treating resistant gram-negative infections. This study evaluated renal safety using KDIGO and RIFLE criteria.
Area of Science:
- Infectious Diseases
- Nephrology
- Pharmacology
Background:
- The RESTORE-IMI 1 trial compared imipenem/cilastatin with relebactam (IMI/REL) to colistin plus imipenem for imipenem-nonsusceptible gram-negative infections.
- Observed differences in nephrotoxicity between treatment arms necessitated further investigation due to the lack of a standardized definition in clinical trials.
Purpose of the Study:
- To retrospectively evaluate and compare the renal safety profiles of IMI/REL and colistin-based therapy.
- To analyze nephrotoxicity using established acute kidney injury criteria and assess renal adverse events.
Main Methods:
- Retrospective analysis of nephrotoxicity using Kidney Disease Improving Global Outcomes (KDIGO) and Risk, Injury, Failure, Loss, and End-stage Kidney Disease (RIFLE) criteria.
- Evaluation of time to onset of nephrotoxicity and incidence of renal adverse events.
Main Results:
- No participants receiving IMI/REL experienced stage 3 acute kidney injury by KDIGO criteria, compared to 31.3% in the colistin plus IMI group.
- No renal failure occurred with IMI/REL by RIFLE criteria, versus 25.0% with colistin plus IMI.
- Fewer renal adverse events (12.9% vs 37.5%) and drug-related renal adverse event discontinuations (0% vs 12.5%) were observed with IMI/REL.
Conclusions:
- IMI/REL demonstrated a more favorable renal safety profile compared to colistin-based therapy.
- These findings support the use of IMI/REL in patients with serious, imipenem-nonsusceptible gram-negative bacterial infections, highlighting its improved kidney safety.
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