TY - JOUR
T1 - Investigating the need for therapeutic drug monitoring of imipenem in critically ill patients
T2 - Are we getting it right?
AU - Mitton, B.
AU - Paruk, F.
AU - Gous, A.
AU - Chausse, J.
AU - Milne, M.
AU - Becker, P.
AU - Said, M.
N1 - Funding Information:
Declaration. None. Acknowledgements. The authors would like to thank Dr Edward Bassey, who assisted with the analysis of specimens. Author contributions. BM designed the study, developed the protocol, recruited participants, collected specimens, processed specimens, collected data, analysed data, drafted and revised the article. He is the guarantor. FP designed the study, recruited participants, provided clinical oversight and revised the article. AG designed the study, analysed the specimens, did the pharmacological calculations and revised the article. JC recruited participants, collected specimens, processed specimens and collected data. MM analysed the specimens. PB did the statistical analysis. MS designed the study, revised the protocol, reviewed the data analysis and revised the article. Funding. This project was partially funded by a Federation of Infectious Diseases Societies of South Africa (FIDSSA) – GlaxoSmithKline (GSK) Research Fellowship. The funding body had no input into the design of the study, the collection, analysis or interpretation of the data or the writing of the manuscript. Conflicts of interest. None.
Publisher Copyright:
© 2021 South African Medical Association. All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - Background. The drug levels and clearances of imipenem in critically ill patients are not comprehensively described in current literature, yet it is vital that adequate levels be achieved for therapeutic success. Objectives. To determine the proportion of critically ill patients treated with imipenem/cilastatin with sub-therapeutic imipenem plasma levels, and to compare the clinical outcomes of those patients with therapeutic levels with those who had sub-therapeutic levels. Methods. Trough imipenem plasma levels of 68 critically ill patients from a surgical intensive care unit were measured using a validated high-performance liquid chromatography method. Imipenem trough levels were compared with the minimum inhibitory concentration (MIC) of the causative bacterial agents, based on a target value of 100% time above MIC (ƒT >MIC). Results. The proportion of participants with sub-therapeutic imipenem levels was 22% (95% confidence interval (CI) 13% - 34%). The 14- and 28-day mortality rates in the sub-therapeutic group were 33% and 40%, respectively, compared with 19% (p=0.293) and 26% (p=0.346), respectively, in the therapeutic group. Sub-therapeutic imipenem plasma levels are associated with adjusted hazard ratio of 1.47 (95% CI 0.55 - 3.91). Conclusions. The lower proportion of critically ill patients with sub-therapeutic imipenem plasma levels in this study compared with previous studies may be attributed to the practice of higher dosages and the administration method of extended infusions of imipenem/ cilastatin in our setting. The results demonstrate a trend of higher mortality in patients with sub-therapeutic imipenem levels, although the results were not statistically significant at this sample size.
AB - Background. The drug levels and clearances of imipenem in critically ill patients are not comprehensively described in current literature, yet it is vital that adequate levels be achieved for therapeutic success. Objectives. To determine the proportion of critically ill patients treated with imipenem/cilastatin with sub-therapeutic imipenem plasma levels, and to compare the clinical outcomes of those patients with therapeutic levels with those who had sub-therapeutic levels. Methods. Trough imipenem plasma levels of 68 critically ill patients from a surgical intensive care unit were measured using a validated high-performance liquid chromatography method. Imipenem trough levels were compared with the minimum inhibitory concentration (MIC) of the causative bacterial agents, based on a target value of 100% time above MIC (ƒT >MIC). Results. The proportion of participants with sub-therapeutic imipenem levels was 22% (95% confidence interval (CI) 13% - 34%). The 14- and 28-day mortality rates in the sub-therapeutic group were 33% and 40%, respectively, compared with 19% (p=0.293) and 26% (p=0.346), respectively, in the therapeutic group. Sub-therapeutic imipenem plasma levels are associated with adjusted hazard ratio of 1.47 (95% CI 0.55 - 3.91). Conclusions. The lower proportion of critically ill patients with sub-therapeutic imipenem plasma levels in this study compared with previous studies may be attributed to the practice of higher dosages and the administration method of extended infusions of imipenem/ cilastatin in our setting. The results demonstrate a trend of higher mortality in patients with sub-therapeutic imipenem levels, although the results were not statistically significant at this sample size.
UR - http://www.scopus.com/inward/record.url?scp=85114408526&partnerID=8YFLogxK
U2 - 10.7196/SAMJ.2021.v111i9.15634
DO - 10.7196/SAMJ.2021.v111i9.15634
M3 - Article
AN - SCOPUS:85114408526
SN - 0256-9574
VL - 111
SP - 903
EP - 909
JO - South African Medical Journal
JF - South African Medical Journal
IS - 9
ER -