| Summary: | 碩士 === 高雄醫學大學 === 藥學系臨床藥學碩士班 === 106 === Background
Infections with gram-negative bacteria (GNB) are common in intensive care units (ICUs) and associated with high mortality. Owing to the paucity of new antibiotics and the increasing incidence of multidrug resistance GNB, colistin becomes the last therapeutic option, especially for the infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii. Nonetheless, colistin is associated with acute kidney injury (AKI) with the incidence rate varying from 14 to 74%. In order to minimize the renal toxicity associated with the use of colistin, it is necessary to conduct studies comprehensively to understand the epidemiology and risk factors of the nephrotoxicity associated with colistin.
Study Aim
1. To conduct a meta-analysis mainly focusing on the nephrotoxicity between colistin-based versus other antibiotics and different therapeutic strategies of colistin.
2. To evaluate the pharmacoepidemiology of colistin and summarizing the risk factors of colistin-association AKI in hospital at Southern Taiwan.
Methods
This study composed of two parts. The first, a meta-analysis was performed. Electronic databases of PubMed, EMBase and Cochrane library were searched up to April 2018 and all the reference lists of relevant articles were screened, enrolling all cohort studies and randomized controlled trials (RCT) with two-arm compartments of colistin-based antibiotic treatments for patients with GNB infections. The primary endpoint was the nephrotoxicity between the treatment of colistin-based versus other antibiotics and different therapeutic strategies of colistin (as monotherapy versus combination therapy, whether given high dose, loading dose or adjunctive inhaled colistin). Secondary endpoint was the overall mortality between colistin-based versus other antibiotics.
Section of pharmacoepidemiology were conducted as a retrospective cohort study in the medical intensive care unit (MICU) of Kaohsiung Medical University (KMU), a medical center at Southern Taiwan. Patient population was those received the first dose of colistin in MICU or within 48 hours prior to MICU for at least 48 hours. The primary outcome was the development of AKI within 7 days after the initiation of colistin. The secondary outcomes were whether patients need renal replacement therapy and overall mortality. By KDIGO criteria, AKI was defined as serum creatinine increased 1.5 times within 7 days or increased 0.3 mg/dL in 2 days after administration of colistin. The risk factors of colistin-associated AKI were evaluated using univariate and multivariate logistic regressions.
Results
In meta-analysis, colistin was associated with two times higher incidence rate of AKI than other antibiotics, without significant difference in mortality. IV colistin, higher dose and giving loading dose were the factors that would increase the AKI rate. Colistin co-administrated with nephrotoxins may lead to higher rate of AKI but co-administrated with carbapenem would result in lower incidence rate of AKI.
In retrospective cohort study, the incidence rate of colistin-associated AKI was 47.6%, the severity was mild to moderate. Colistin-associated AKI was reversible and was not related to the overall mortality. Vasopressor was an independent factor related to colistin-associated AKI. Colistin co-administrated with carbapenem also showed a trend with lower AKI rate.
Conclusion
Colistin was related to a higher incidence rate of AKI compared with other antibiotics. The incidence rate of colistin-associated AKI was 47.6%, the severity was mild to moderate. It was reversible and was not related to the overall mortality. Higher dose, giving loading dose, co-administrated with nephrotoxins and required of vasopressor may lead to higher risk of AKI. Co-administrated with carbapenem showed a trend with lower AKI rate. Whether co-administrated carbapenem can lower the AKI rate are necessary to be carryout by other studies.
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