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

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.

SUBMITTER: Burnham JP

PROVIDER: S-EPMC5497982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCommunity-onset bloodstream infection (CO-BSI) is associated with substantial morbidity and mortality. Knowledge of locally prevalent pathogens and antimicrobial susceptibility patterns can promptly guide appropriate empiric therapy and improve outcomes.ObjectivesWe sought to determine the epidemiology of CO-BSI, the blood culture positivity rate and the contamination rate. We also sought to establish appropriateness of current empiric antimicrobial therapy practices.MethodsWe retrospectively analyzed blood cultures taken from January 2015 to December 2019 at the emergency departments (EDs) of a tertiary-care academic hospital in South Africa using extracted laboratory data.ResultsThe overall positivity rate of blood cultures taken at the EDs was 15% (95% confidence interval [CI], 0.15-0.16) and the contamination rate was 7% (95% CI, 0.06-0.07). Gram-positive bacteria predominated in the pediatric cohort: neonates, 52 (54%) of 96; infants, 57 (52%) of 109; older children, 63 (61%) of 103. Methicillin-susceptible Staphylococcus aureus was the predominant pathogen among older children: 30 (35%) of 85. Escherichia coli was the most common pathogen isolated among adults and the elderly: 225 (21%) of 1,060 and 62 (29%) of 214, respectively. Among neonates, the susceptibility of E. coli and Klebsiella pneumoniae to the combination of ampicillin and gentamicin was 17 (68%) of 25. Among adults, the susceptibility of the 5 most common pathogens to amoxicillin-clavulanate was 426 (78%) of 546 and their susceptibility to ceftriaxone was 481 (85%) of 565 (P = .20). The prevalence of methicillin-resistant S. aureus, extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacterales were low among all age groups.ConclusionsReview of blood culture collection techniques is warranted to reduce the contamination rate. High rates of resistance to currently prescribed empiric antimicrobial agents for CO-BSI warrants a re-evaluation of local guidelines.

Project description:BackgroundThe purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance.MethodsThis is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m2) and without ARC.ResultsTwenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range.ConclusionsARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC.Clinical trial registrationThis study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838 .

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

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