Evaluating the usefulness of the estimated glomerular filtration rate for determination of imipenem dosage in critically ill patients

Authors

  • B Mitton Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; Universitas Academic Laboratory Complex, National Health Laboratory Service, Pretoria, South Africa
  • F Paruk Department of Critical Care, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa; Department of Critical Care, Steve Biko Academic Hospital, Pretoria, South Africa
  • A Gous School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, South Africa
  • J Chausse Department of Critical Care, Steve Biko Academic Hospital, Pretoria, South Africa
  • M Milne School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, South Africa
  • P Becker Department of Biostatistics, Faculty of Health Sciences, University of Pretoria, South Africa
  • M Said Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, South Africa; Tshwane Academic Division, National Health Laboratory Service, Pretoria, South Africa

DOI:

https://doi.org/10.7196/SAMJ.2022.v112i9.16371

Keywords:

Renal fuction, Bacterial

Abstract

Background. Antibiotic dosing in critically ill patients is complicated by variations in the pharmacokinetics of antibiotics in this group. The dosing of imipenem/cilastatin is usually determined by severity of illness and renal function.
Objectives. To determine the correlation between estimated glomerular filtration rates (eGFRs) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and imipenem trough levels in critically ill patients.
Methods. This prospective observational study was done in the surgical intensive care unit (ICU) at Steve Biko Academic Hospital, Pretoria, South Africa. Imipenem trough levels were measured by high-performance liquid chromatography and compared with eGFRs calculated with the CKD-EPI equation. Correlation was evaluated by the Pearson product-moment correlation coefficient.
Results. The study population consisted of 68 critically ill patients aged between 18 and 81 years; 43 (63%) were male, and the mean weight was 78 kg (range 40 - 140). On admission, 30 patients (44%) had sepsis, 16 (24%) were admitted for trauma, and 22 (32%) were admitted for miscellaneous surgical conditions. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ranged from 4 to 39 (mean 18). The 28-day mortality rate was 29%. The mean albumin level was 16 g/L (range 7 - 25), the mean creatinine level 142 μmol/L (range 33 - 840), and the mean eGFR 91 mL/min/1.73 m2 (range 6 - 180). Imipenem trough levels ranged between 3.6 and 92.2 mg/L (mean 11.5). The unadjusted Pearson product-moment correlation coefficient between eGFR and imipenem trough level was –0.04 (p=0.761).
Conclusion. Considering the high mortality rate of sepsis in ICUs and the rapid global increase in antimicrobial resistance, it is crucial
to dose antibiotics appropriately. Owing to the variability of antibiotic pharmacokinetics in critically ill patients, this task becomes almost impossible when relying on conventional dosing guidelines. This study found that eGFRs do not correlate with imipenem blood levels in critically ill patients and should not be used to determine the dose of imipenem/cilastatin. Instead, the dose should be individualised for patients through routine therapeutic drug monitoring.

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Published

2022-08-30

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Research

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1.
Mitton B, Paruk F, Gous A, Chausse J, Milne M, Becker P, et al. Evaluating the usefulness of the estimated glomerular filtration rate for determination of imipenem dosage in critically ill patients. S Afr Med J [Internet]. 2022 Aug. 30 [cited 2025 Mar. 23];112(9). Available from: https://samajournals.co.za/index.php/samj/article/view/765-768