LARGE-SCALE, MULTICENTER, RETROSPECTIVE STUDY ON NEPHROTOXICITY ASSOCIATED WITH EMPIRIC, BROAD-SPECTRUM ANTIBIOTICS IN CRITICALLY ILL PATIENTS

Abstract

SESSION TITLE: Late Breaking Investigations From Pulmonary and Critical CareSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: Empiric broad-spectrum antibiotic regimens are widely used in the initial management of critically ill patients with suspected infection, notably vancomycin with piperacillin/tazobactam (VPT), cefepime (VC), and meropenem (VM). However, there is conflicting evidence regarding acute kidney injury (AKI) associated with these empiric antibiotic regimens in intensive care unit (ICU) patients.METHODS: This large multi-center retrospective cohort study was conducted using the eICU® Research Institute database 21,22. Patients were included if they exclusively received VPT, VM or VC on ICU admission and were admitted from the emergency department. Patients on dialysis prior to antibiotic administration were excluded. SCr was defined as the lowest SCr value within the window of ICU admission.38 The primary outcome was AKI in the first week following antibiotic exposure. To mitigate the effects of pseudo-nephrotoxicity and incidental fluctuations in SCr, a stringent definition of AKI was used.2 An outcome of AKI was defined as Stage 2 or 3, as outlined via the Kidney Disease: Improving Global Outcomes guidelines based on the SCr component alone24. Propensity score matching was performed on the following features: age, eGFR, immunocompromised state, the APACHE IV, BMI, and nephrotoxic agents. Two further sub-analyses were conducted to study the effect of longer treatment durations ((≥ 48 hours) and normal initial kidney function (eGFR > 60) on AKI risk between the treatment groups25.RESULTS: A total of 267,216 patients comprised our cohort after applying the exclusion criteria. All patients were successfully matched one-to-one with replacement via propensity score matching. Across each matched cohort, age, APACHE score, baseline eGFR, and immunocompromised status were comparable. The odds of AKI for patients receiving VPT were significantly higher than that of similar patients receiving VC or VM (VPT vs. VC: OR, 1.37; 95% CI, [1.25-1.49]]; VPT vs. VM: OR, 1.27; 95% CI, [1.06-1.52]). For patients with normal initial renal function, this effect was even more pronounced (VPT vs. VC: OR, 1.59; 95% CI, [1.37-1.82]]; VPT vs. VM: OR, 1.61; 95% CI, [1.20-2.17]). For patients with ≥ 48 hours of treatment, patients receiving VPT had higher odds of developing AKI than when compared to similar patients receiving VC or VM (VPT vs VC: OR, 1.47; 95% CI, [1.28-1.69]; VPT vs VM: OR, 1.75; 95% CI, [1.33-2.33]).CONCLUSIONS: Our multi-center retrospective cohort study is the largest study on the association of nephrotoxicity and empiric antibiotic regimens in the critically ill population. VPT was associated with an increased risk of AKI compared with VC or VM, especially in patients with normal kidney function on admission receiving a longer duration of antibiotic treatment.CLINICAL IMPLICATIONS: Clinicians and institutions should consider the associated risk of AKI in VPT when initiating broad-spectrum antibiotics.DISCLOSURES:No relevant relationships by Miguel Ángel Armengol de la HozNo relevant relationships by Christian BeckerNo relevant relationships by paola calvachiNo relevant relationships by paola calvachiNo relevant relationships by Leo Anthony CeliNo relevant relationships by Alyssa ChenEmployee relationship with Google Please note: 7/2019-Current Added 06/02/2022 by Christina Chen, value=SalaryNo relevant relationships by Alon DaganNo relevant relationships by Chih-Ying DengNo relevant relationships by Alistair JohnsonNo relevant relationships by Afeefah Khazi-SyedAdvisory Committee Member relationship with Philips Please note: 2016 - Present Added 06/03/2022 by Corey Scurlock, value=Travel SESSION TITLE: Late Breaking Investigations From Pulmonary and Critical Care SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Empiric broad-spectrum antibiotic regimens are widely used in the initial management of critically ill patients with suspected infection, notably vancomycin with piperacillin/tazobactam (VPT), cefepime (VC), and meropenem (VM). However, there is conflicting evidence regarding acute kidney injury (AKI) associated with these empiric antibiotic regimens in intensive care unit (ICU) patients. METHODS: This large multi-center retrospective cohort study was conducted using the eICU® Research Institute database 21,22. Patients were included if they exclusively received VPT, VM or VC on ICU admission and were admitted from the emergency department. Patients on dialysis prior to antibiotic administration were excluded. SCr was defined as the lowest SCr value within the window of ICU admission.38 The primary outcome was AKI in the first week following antibiotic exposure. To mitigate the effects of pseudo-nephrotoxicity and incidental fluctuations in SCr, a stringent definition of AKI was used.2 An outcome of AKI was defined as Stage 2 or 3, as outlined via the Kidney Disease: Improving Global Outcomes guidelines based on the SCr component alone24. Propensity score matching was performed on the following features: age, eGFR, immunocompromised state, the APACHE IV, BMI, and nephrotoxic agents. Two further sub-analyses were conducted to study the effect of longer treatment durations ((≥ 48 hours) and normal initial kidney function (eGFR > 60) on AKI risk between the treatment groups25. RESULTS: A total of 267,216 patients comprised our cohort after applying the exclusion criteria. All patients were successfully matched one-to-one with replacement via propensity score matching. Across each matched cohort, age, APACHE score, baseline eGFR, and immunocompromised status were comparable. The odds of AKI for patients receiving VPT were significantly higher than that of similar patients receiving VC or VM (VPT vs. VC: OR, 1.37; 95% CI, [1.25-1.49]]; VPT vs. VM: OR, 1.27; 95% CI, [1.06-1.52]). For patients with normal initial renal function, this effect was even more pronounced (VPT vs. VC: OR, 1.59; 95% CI, [1.37-1.82]]; VPT vs. VM: OR, 1.61; 95% CI, [1.20-2.17]). For patients with ≥ 48 hours of treatment, patients receiving VPT had higher odds of developing AKI than when compared to similar patients receiving VC or VM (VPT vs VC: OR, 1.47; 95% CI, [1.28-1.69]; VPT vs VM: OR, 1.75; 95% CI, [1.33-2.33]). CONCLUSIONS: Our multi-center retrospective cohort study is the largest study on the association of nephrotoxicity and empiric antibiotic regimens in the critically ill population. VPT was associated with an increased risk of AKI compared with VC or VM, especially in patients with normal kidney function on admission receiving a longer duration of antibiotic treatment. CLINICAL IMPLICATIONS: Clinicians and institutions should consider the associated risk of AKI in VPT when initiating broad-spectrum antibiotics. DISCLOSURES: No relevant relationships by Miguel Ángel Armengol de la Hoz No relevant relationships by Christian Becker No relevant relationships by paola calvachi No relevant relationships by paola calvachi No relevant relationships by Leo Anthony Celi No relevant relationships by Alyssa Chen Employee relationship with Google Please note: 7/2019-Current Added 06/02/2022 by Christina Chen, value=Salary No relevant relationships by Alon Dagan No relevant relationships by Chih-Ying Deng No relevant relationships by Alistair Johnson No relevant relationships by Afeefah Khazi-Syed Advisory Committee Member relationship with Philips Please note: 2016 - Present Added 06/03/2022 by Corey Scurlock, value=Travel