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A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Optimization of antimicrobial dosing in patients with acute kidney injury: a single-centre observational study
Stephen Hughes1, Katie L Heard1, Nabeela Mughal1
1Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK.
Background:
Acute kidney injury (AKI) is a potential complication of systemic infection. Optimizing antimicrobial dosing in this dynamic state can be challenging with sub- or supra-therapeutic dosing risking treatment failure or toxicity, respectively. Locally, unadjusted renal dosing for the first 48 h of infection is recommended.
Objectives:
To determine the outcomes associated with this dosing strategy.
Methods:
A retrospective cohort analysis was undertaken in patients treated for Gram-negative bacteraemia with concurrent non-filtration dependent AKI from a single-centre NHS acute hospital (April 2016-March 2020). Patient demographics, microbiology data, antimicrobial treatment and patient outcome (in-hospital mortality and kidney function) were analysed.
Results:
In total, 647 episodes of Gram-negative bacteraemia (608 patients) were included; 305/608 (50.2%) were male with median age 71 years (range 18-100). AKI was present in 235/647 (36.3%); 78/647 (12.1%) and 45/647 (7.0%) having Kidney Disease Improving Global Outcomes-defined injury (stage 2) or failure (stage 3), respectively. In-hospital 30 day mortality was 25/352 (7.1%), 14/112 (12.5%), 26/123 (21.1%) and 11/60(18.3%) in patients with normal renal function, AKI stage 1, AKI stage ≥2 and established chronic kidney disease, respectively. Recovery of renal function at Day 21 or discharge was present in 105/106 surviving patients presenting with AKI stage ≥2. Time to recovery of AKI was similar in patients receiving full, low or no aminoglycoside (3 versus 4 versus 3 days, P = 0.612) and those receiving full- and low-dose β-lactam (3 versus 5 days, P = 0.077).
Conclusions:
There is a high burden of AKI in patients with Gram-negative bacteraemia. Dose adjustments of β-lactams may not be necessary in the first 48 h of infection-induced AKI and single-dose aminoglycosides may be considered for early empirical coverage.
Insights
Acute kidney injury (AKI) is common in Gram-negative bacteraemia. Unadjusted antimicrobial dosing for the initial 48 hours of AKI may be safe and effective, supporting current recommendations.
Area of Science:
- Nephrology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Acute kidney injury (AKI) frequently complicates systemic infections like Gram-negative bacteraemia.
- Optimizing antimicrobial drug dosing during AKI is critical to prevent treatment failure or toxicity.
- Current guidelines often recommend unadjusted renal dosing for the initial 48 hours of infection-induced AKI.
Purpose of the Study:
- To evaluate the clinical outcomes of patients with Gram-negative bacteraemia and concurrent AKI who received unadjusted antimicrobial dosing for the first 48 hours.
- To assess the impact of this dosing strategy on mortality and kidney function recovery.
Main Methods:
- A retrospective cohort study was conducted on patients with Gram-negative bacteraemia and non-filtration dependent AKI.
- Data collected included demographics, microbiology, antimicrobial treatments, in-hospital mortality, and kidney function.
- Analysis focused on outcomes related to the initial 48-hour dosing strategy.
Main Results:
- AKI was present in 36.3% of Gram-negative bacteraemia episodes.
- In-hospital mortality varied by AKI severity, with higher rates in patients with more severe AKI or chronic kidney disease.
- Renal function recovery was observed in most surviving patients with AKI stage ≥2.
- Time to AKI recovery was similar across different aminoglycoside and beta-lactam dosing strategies.
Conclusions:
- A significant burden of AKI exists in patients with Gram-negative bacteraemia.
- Dose adjustments for beta-lactams may not be required in the initial 48 hours of infection-induced AKI.
- Single-dose aminoglycosides can be considered for early empirical therapy in this patient population.
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