Utilization of Colistin Versus β-Lactam and β-Lactamase Inhibitor Agents in Relation to Acute Kidney Injury in Patients with Severe Gram-Negative Infections

Background. Colistin is a lifesaving treatment for multidrug-resistant Gram-negative bacterial (MDR-GNB) infections along with its well-known nephrotoxicity. The controversy of colistin-induced acute kidney injury (AKI) on mortality is noted. This study aimed to determine the risk factors and impact of AKI on the survival and significance of colistin dosage. Methods. A retrospective cohort study was performed in adult patients who received intravenous colistin for MDR-GNB treatment between June 2015 and June 2017. Factors influencing colistin-induced AKI and survival were evaluated by Cox regression analysis. Cut-off levels of the colistin dose per ideal body weight (IBW) that significantly affected clinical outcomes were assessed with linearity trends and receiver operating characteristic analyses. Results. AKI occurred in 68.5% of 412 enrolled patients with an incidence rate of 10.6 per 100 patients-days and a median time was 6 (3–13) days. Stages I–III of AKI were 38.3, 24.5, and 37.2%. Factors associated with colistin-induced AKI were advanced age, high serum bilirubin, AKI presented before colistin administration, increased daily colistin doses per IBW, and concomitant use of nephrotoxic drugs. Colistin-induced AKI was related to mortality (HR 1.74, 95% CI 1.06–2.86, p = 0.028 ). In the non-AKI before colistin usage subgroup, the total dose and total dose/IBW were >1,500–2,000 mg and 30–35 mg/kg to benefit mortality reduction but were <2,500–3,000 mg and 45–50 mg/kg for risk reduction of AKI. A daily colistin dose/IBW >4.5 mg/kg/day also increased the risk of AKI. In the AKI developed before colistin subgroup, the cut-off values of total colistin dose >1250–1350 mg and total dose/IBW >23.5–24 mg/kg demonstrated significant risks of AKI. Conclusion. The incidence of AKI after colistin administration was high and impacted mortality. Prevention and early correction of these related factors are mandatory. Careful use of colistin was also both beneficial in mortality and AKI reductions.

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Acute Kidney Injury in Patients Treated with IV Beta-Lactam/Beta-Lactamase Inhibitor Combinations

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy ◽

10.1002/phar.1918 ◽

2017 ◽

Vol 37 (5) ◽

pp. 593-598 ◽

Cited By ~ 10

Author(s):

W. Cliff Rutter ◽

David S. Burgess

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Beta Lactamase ◽

Beta Lactam ◽

Lactamase Inhibitor

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Evaluation of Renal Safety Between Imipenem/Relebactam and Colistin Plus Imipenem in Patients With Imipenem-Nonsusceptible Bacterial Infections in the Randomized, Phase 3 RESTORE-IMI 1 Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa054 ◽

2020 ◽

Vol 7 (3) ◽

Author(s):

Michelle L Brown ◽

Johann Motsch ◽

Keith S Kaye ◽

Thomas M File ◽

Helen W Boucher ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Disease ◽

Adverse Events ◽

Safety Profile ◽

Bacterial Infections ◽

Kidney Injury ◽

Gram Negative ◽

End Stage ◽

Time To Onset ◽

Renal Safety

Abstract 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. ClinicalTrials.gov Identifier NCT02452047.

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