Aminoglycosides in Critically Ill Septic Patients With Acute Kidney Injury Receiving Intermittent Hemodialysis: A Multicenter, Observational Study.

PURPOSE: Data on aminoglycoside stewardship in critically ill septic patients with acute kidney injury (AKI) needing intermittent hemodialysis (IH) are scarce. The first objective of the study was to evaluate whether aminoglycoside administration occurs before vs after IH in the real-life management of critically ill septic patients with AKI needing IH. The second objective was to assess the delay in achieving a potential reinjection window for a second dose of aminoglycoside, which should be obtained with a postdialysis vs predialysis regimen. METHODS: A post hoc observational analysis of a multicenter randomized trial of critically ill patients with AKI needing renal replacement therapy was conducted. Inclusion criteria consisted of any patients receiving IH for AKI during an antimicrobial therapy for a septic episode. FINDINGS: Among 206 of 341 septic patients (60%) receiving aminoglycosides, 90 underwent IH (46 with previous continuous renal replacement therapy and 44 without). Amikacin and gentamicin were administered for a mean (SD) of 2.2 (1.5) and 2.5 (2.1) days with mean (SD) doses of 20.6 (6.6) and 5.4 (2.5) mg/kg, respectively. In the 44 patients undergoing exclusive IH, aminoglycosides were administered in a predialysis in 53% of episodes versus 35% in a postdialysis schedule. The first Cmin target was obtained earlier with a predialysis vs postdialysis schedule (33.9 [14.2] hours vs 50.9 [12.2] hours, P = 0.009). IMPLICATIONS: Despite being less frequently used than a predialysis schedule, the postdialysis administration of aminoglycosides remains a regular practice in the intensive care unit. A predialysis schedule of administration in IH reduces the interval time to tolerable aminoglycoside redosing.

Aminoglycosides in Critically Ill Septic Patients With Acute Kidney Injury Receiving Continuous Renal Replacement Therapy: A Multicenter, Observational Study.

PURPOSE: Data on aminoglycoside stewardship in critically ill septic patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) are scarce. The objectives of the study were to determine, during CRRT, the time window with low likelihood for safe reinjection and the proportion of inappropriate reinjection. METHODS: A post hoc observational analysis of a multicenter randomized trial comparing the risk of hemodialysis catheter infection with ethanol lock vs placebo in critically ill patients with AKI was conducted. Eligible patients were adults in intensive care units from 6 French hospitals. Any patient with AKI needing CRRT and receiving an antimicrobial therapy for a septic episode occurring before (≤24 hours) or during CRRT was included. The aminoglycoside orders were left to the physicians' discretion, but high dose once daily was the schedule of aminoglycoside administration. FINDINGS: A total of 145 septic episodes treated by aminoglycosides were analyzed in patients receiving CRRT. A mean (SD) of 1.6 (0.8) amikacin and 1.8 (1.2) gentamicin administrations per patient were observed. During CRRT, Cmax was 17.3 mg/L (interquartile range, 13.2-22.5 mg/L) for gentamicin and 50 mg/L (interquartile range, 43.7-76.6 mg/L) for amikacin. The plasma drug concentration at 24 hours (CH24) was 2.3 mg/L (interquartile range, 1.6-3.2 mg/L) for gentamicin and 9.3 (interquartile range, 6.6-12.0 mg/L) for amikacin. Sixty-five Cmin dosages remained above the reinjection threshold. Inappropriate reinjection was observed in 11 of 65 episodes (17%). Inappropriate reinjection (defined by, at the reinjection time, Cmin dosages above the threshold; ie, Cmin >2 mg/L for gentamicin and >5 mg/L for amikacin) was observed in 17% of analyzed episodes. Most patients did not need reinjection until approximately ≥30 hours after their initial administration. IMPLICATIONS: During CRRT, as indicated by the CH24 value, which was higher than the recommended threshold, the interval to obtain a Cmin low enough to allow for redosing aminoglycosides is significantly longer than 24 hours. This interval is not always respected and leads to an of inappropriate reinjection rate of 17%. ClinicalTrials.gov identifier: ISRCTNCT00875069.

High creatinine clearance in critically ill patients with community-acquired acute infectious meningitis.

BACKGROUND: A high dose of anti-infective agents is recommended when treating infectious meningitis. High creatinine clearance (CrCl) may affect the pharmacokinetic / pharmacodynamic relationships of anti-infective drugs eliminated by the kidneys. We recorded the incidence of high CrCl in intensive care unit (ICU) patients admitted with meningitis and assessed the diagnostic accuracy of two common methods used to identify high CrCl. METHODS: Observational study performed in consecutive patients admitted with community-acquired acute infectious meningitis (defined by >7 white blood cells/mm3 in cerebral spinal fluid) between January 2006 and December 2009 to one medical ICU. During the first 7 days following ICU admission, CrCl was measured from 24-hr urine samples (24-hr-UV/P creatinine) and estimated according to Cockcroft-Gault formula and the simplified Modification of Diet in Renal Disease (MDRD) equation. High CrCl was defined as CrCl >140 ml/min/1.73 m2 by 24-hr-UV/P creatinine. Diagnostic accuracy was performed with ROC curves analysis. RESULTS: Thirty two patients were included. High CrCl was present in 8 patients (25%) on ICU admission and in 15 patients (47%) during the first 7 ICU days for a median duration of 3 (1-4) days. For the Cockcroft-Gault formula, the best threshold to predict high CrCl was 101 ml/min/1.73 m2 (sensitivity: 0.96, specificity: 0.75, AUC = 0.90 ± 0.03) with a negative likelihood ratio of 0.06. For the simplified MDRD equation, the best threshold to predict high CrCl was 108 ml/min/1.73 m2 (sensitivity: 0.91, specificity: 0.80, AUC = 0.88 ± 0.03) with a negative likelihood ratio of 0.11. There was no difference between the estimated methods in the diagnostic accuracy of identifying high CrCl (p = 0.30). CONCLUSIONS: High CrCl is frequently observed in ICU patients admitted with community-acquired acute infectious meningitis. The estimated methods of CrCl could be used as a screening tool to identify high CrCl.