Research Article: Augmented renal clearance is not a risk factor for mortality in Enterobacteriaceae bloodstream infections treated with appropriate empiric antimicrobials

Date Published: July 5, 2017

Publisher: Public Library of Science

Author(s): Jason P. Burnham, Scott T. Micek, Marin H. Kollef, Scott Brakenridge.

http://doi.org/10.1371/journal.pone.0180247

Abstract

The main objective of the study was to assess whether augmented renal clearance was a risk factor for mortality in a cohort of patients with Enterobacteriaceae sepsis, severe sepsis, or septic shock that all received appropriate antimicrobial therapy within 12 hours. Using a retrospective cohort from Barnes-Jewish Hospital, a 1,250-bed teaching hospital, we collected data on individuals with Enterobacteriaceae sepsis, severe sepsis, and septic shock who received appropriate initial antimicrobial therapy between June 2009 and December 2013. Clinical outcomes were compared according to renal clearance, as assessed by Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, sepsis classification, demographics, severity of illness, and comorbidities. We identified 510 patients with Enterobacteriaceae bacteremia and sepsis, severe sepsis, or septic shock. Sixty-seven patients (13.1%) were nonsurvivors. Augmented renal clearance was uncommon (5.1% of patients by MDRD and 3.0% by CKD-EPI) and was not associated with increased mortality. Our results are limited by the absence of prospective determination of augmented renal clearance. However, in this small cohort, augmented renal clearance as assessed by MDRD and CKD-EPI does not seem to be a risk factor for mortality in patients with Enterobacteriaceae sepsis. Future studies should assess this finding prospectively.

Partial Text

Augmented renal clearance (ARC) is the term given to the phenomenon of accelerated glomerular filtration resulting in reduced systemic exposure to renally eliminated drugs. The incidence of ARC varies by population studied, being more prevalent in persons with traumatic injuries, persons of younger age, males, and sepsis patients with lower acute physiology and chronic health evaluation (APACHE) II scores [1–4]. While there is no universal agreement on how to best measure ARC [5–9], its effect on antibiotic levels is now well established [10–13]. Multiple studies have shown that patients with ARC have reduced exposure to renally cleared antibiotics, but only one study has shown any effect on outcome [1, 10, 14]. We previously described a cohort of patients with Enterobacteriaceae sepsis, severe sepsis, or septic shock that all received appropriate antibiotics within 12 hours of positive blood cultures and found that cirrhosis, African-American race, and presence of septic shock were risk factors for mortality [15]. As these three factors have been associated with hyperdynamic cardiac output and thereby potentially ARC, we performed a secondary analysis of our previous cohort with the goal of determining whether ARC was prevalent and whether it impacted mortality in a group of patients all receiving appropriate empiric antibiotic therapy.

Five-hundred ten patients with sepsis, severe sepsis, or septic shock (by SIRS criteria) due to Enterobacteriaceae met the inclusion criteria. After exclusion of 16 patients with end-stage renal disease, there were 494 patients for which GFR was calculated. Baseline characteristics of the patients stratified by GFR are listed in Table 1. Augmented renal clearance was present in a minority of patients using values obtained from MDRD (5.1%, n = 25) and CKD-EPI (3.0%, n = 15) calculations. In univariate analysis, age, APACHE II and Charlson Comorbidity scores, and presence of CHF or African-American race were significantly different between the ARC and no ARC groups. Age, Charlson comorbidity and APACHE II scores were lower in patients with ARC. African-American race was more common in the ARC group, whereas CHF was absent. In our sensitivity analysis, we used a GFR cutoff of 100 mL/min/1.73 m2 to identify patients with possible ARC (pARC). Using the MDRD calculation, 83 patients (16.8%) had pARC. By CKD-EPI calculations, 82 patients (16.6%) had pARC. Table 2 provides a detailed breakdown of GFR for the population as calculated by MDRD and CKD-EPI equations.

We found that ARC was not a predictor of mortality among patients with Enterobacteriaceae bloodstream infections receiving appropriate initial antimicrobial therapy within 12 hours of positive blood cultures being drawn. Predictors of mortality in the cohort were African-American race, transfer from an OSH, increasing APACHE-II scores, underlying malignancy, and cirrhosis, which are known risk factors for mortality in sepsis and reflect acute and chronic illness severity [15]. Interestingly, the percentage of patients with ARC was <5%, much lower than reported rates in the literature [1–5, 7, 10, 20, 21]. However, ARC varies by patient population, being more common in trauma and younger patients, which were not the predominant demographics of our cohort. In addition, we assessed ARC retrospectively without measured urinary creatinine clearance, which is known to underestimate the prevalence of ARC by up to 30% [5–9].   Source: http://doi.org/10.1371/journal.pone.0180247

 

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