Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching

Abstract

Background Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity. Objectives To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis. Patients and methods The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy. Results A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (β = −0.023; 95% CI = −12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (β = 0.299; 95% CI = −0.38 to 0.98; P = 0.388). Conclusions CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

Account of Deep Learning-Based Ultrasonic Image Feature in the Diagnosis of Severe Sepsis Complicated with Acute Kidney Injury

“…Early inflammatory responses released a large amount of proinflammatory cytokines and anti-inflammatory cytokines [ 8 ]. However, there is often an imbalance between proinflammatory factors and anti-inflammatory factors in sepsis patients, and the inflammatory reaction is out of control, which accelerates the development of sepsis [ 9 – 11 ]. In addition, inflammation often interacts with coagulation dysfunction and then influences the development of sepsis.…”

Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching—authors’ response

“…2,3 Unsurprisingly, the performance of AUC/MIC in predicting outcome was inconsistent in a meta-analysis. 2 In addition, and somewhat surprisingly, there is very little pre-clinical infection model data to support the clinically derived vancomycin pharmacodynamic targets 4 and the use of pre-clinical vancomycin AUC/MIC targets to support the clinical trials would be complicated by issues about the variability of vancomycin protein binding in man and drug inoculum-related effects present for Staphylococcus aureus 5,6 and perhaps other pathogens. In addition, many hospitals may lack the necessary pharmacokinetic expertise to calculate vancomycin AUCs on a routine basis.…”

“…Based on our findings, CCAB can be considered as a safe, first-line antifungal in critically ill patients with suspected or documented invasive candidiasis, pending confirmation or exclusion of the diagnosis and identification of the organism. 6 Further, the respondents state that we ignored the pharmacodynamic data in relation to efficacy. Although our study did not focus on efficacy, we thoroughly addressed the pharmacokinetic and pharmacodynamic properties of amphotericin B in our report.…”

“…In our study, the focus of therapeutic drug monitoring (TDM) was to prevent amphotericin B accumulation and possible nephrotoxicity. 6 The upper limit of 1.0 mg/L was pragmatically chosen, as concentrations >0.5 mg/L result in fungicidal concentrations in the peritoneum. 12 More information on the usefulness of TDM for amphotericin B is required, also in relation to the efficacy of CCAB.…”

“…The costs for a CCAB patient are €14.74 per day, which is low compared with other antifungals. 6 Costs related to efficacy are not known because there are no studies that compare CCAB with other antifungal drugs. There is no need to compare CCAB with fluconazole because patients who are not resistant to fluconazole switch to this drug.…”