Imipenem 500mg / Cilastatin 500mg powder for solution for infusion vials

BackgroundGram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors.ObjectivesThe objective of this study was to collect information on the efficacy and safety of novel β-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL).MethodsIn order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel β-lactamase inhibitor combinations with existing comparator therapies.ResultsFour studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators.ConclusionThe clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.

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Abstract Cilastatin is an inhibitor of drug metabolism in the kidney which is only available for human use in combination with imipenem, a carbapenem antibiotic, as imipenem/cilastatin (I/C). Animal studies demonstrate cilastatin protects against acute kidney injury (AKI) and clinical studies suggest I/C may reduce the risk of AKI. However, the effective dose of cilastatin in animal studies is higher than that approved with imipenem, and rigorous assessment of the effect of I/C on AKI in patients with high risk of AKI, such as those in the intensive care unit (ICU), is indicated. To address this issue, we conducted a retrospective cohort study using 3 large ICU databases, including Medical Information Mart for Intensive Care III (MIMIC-III), MIMIC-IV, and the Amsterdam University Medical Center database (AUMC). Total 3916 patients were included and patients treated with I/C or non-cilastatin carbapenems (NCC) were compared using propensity score-based overlap weighting analysis. AKI development or progression was less commonly observed in I/C-treated patients than in NCC-treated patients in MIMIC-III (odds ratio [OR] and 95% confidence interval of I/C group: 0.51 [0.30–0.85]) while the outcome was similar between the groups in MIMIC-IV (OR: 1.22 [0.80–1.86]) and in AUMC (OR: 1.07 [0.77–1.48]). The outcome development was also similar between the groups with the overall analysis across all datasets by random effect model meta-analysis (OR: 0.89 [0.54–1.48]). In conclusion, I/C and other carbapenems do not differentially associate with AKI risks in ICU, and its putative effects may depend on patient characteristics and clinical settings.

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