Decreasing the time to achieve therapeutic vancomycin concentrations in critically ill patients: developing and testing of a dosing nomogram

Abstract

IntroductionAchievement of optimal vancomycin exposure is crucial to improve the management of patients with life-threatening infections caused by susceptible Gram-positive bacteria and is of particular concern in patients with augmented renal clearance (ARC). The aim of this study was to develop a dosing nomogram for the administration of vancomycin by continuous infusion for the first 24 hours of therapy based on the measured urinary creatinine clearance (8 h CLCR).MethodsThis single-center study included all critically ill patients treated with vancomycin over a 13-month period (group 1), in which we retrospectively assessed the correlation between vancomycin clearance and 8 h CLCR. This data was used to develop a formula for optimised drug dosing. The efficiency of this formula was prospectively evaluated in a second cohort of 25 consecutive critically ill patients (group 2). Vancomycin serum concentrations between 20 to 30 mg/L were considered adequate. ARC was defined as 8 h CLCR more than 130 ml/min/1.73 m2.ResultsThe incidence of ARC was 36% (n = 29/79) and 40% (10/25) in group 1 (n = 79) and 2 (n = 25), respectively. The mean serum vancomycin concentration on day 1 was 21.5 (6.4) and 24.5 (5.2) mg/L, for both groups respectively. On the treatment day, vancomycin plasma clearance was 5.12 (1.9) L/h in group 1 and correlated significantly with the 8 h CLCR (r2 = 0.66; P <0.001). The achievement of adequate vancomycin serum concentrations in group 2 was 84% (n = 21/25) versus 51% (n = 40/79) – P <0.005.ConclusionsThis new vancomycin nomogram enabled the achievement of adequate serum concentrations in 84% of the patients on the first day of treatment.

Application of vancomycin in patients with varying renal function, especially those with augmented renal clearance

“…Furthermore, a recent study in critically ill patients with ARC and administration by continuous infusion showed that vancomycin plasma clearance was correlated significantly with the 8-hour CL cr (Baptista et al 2014).…”

Reliability of serum creatinine‐based formulae estimating renal function in non‐critically ill surgery patients: Focus on augmented renal clearance

“…6 However, in daily practice, we rely on estimating formulae to assess renal function. Therefore, the identified predictors for disagreement can be useful to interpret Because CrCl 8h ≥ 130 mL/min/1.73 m² is an independent risk factor for enhanced clearance of renally excreted antimicrobials, potentially leading to subtherapeutic concentrations, [3][4][5][6][7][8][9]12 and in the absence of routinely performed CrCl 8h in non-ICU surgery patients, we performed a ROC analysis to identify patients displaying ARC with eGFR CKD-EPI . In the absence of an ideal cut-off, defined as the cut-off with both a sensitivity and specificity of 0.95, we pointed out 3 cut-offs with decreasing sensitivity and increasing specificity, respectively.…”

“…Recently, much attention has been paid to “augmented renal clearance” (ARC), which is defined as the enhanced renal (drug) elimination as compared to an expected baseline . In patients admitted to the intensive care unit (ICU), a creatinine clearance (CrCl) ≥130 mL/min/1.73 m² has been identified as a risk factor for enhanced antimicrobial clearance potentially leading to non‐attained pharmacokinetic/pharmacodynamic targets with consequently therapeutic failure and development of bacterial resistance …”

“…1,2 In patients admitted to the intensive care unit (ICU), a creatinine clearance (CrCl) ≥130 mL/min/1.73 m² has been identified as a risk factor for enhanced antimicrobial clearance potentially leading to non-attained pharmacokinetic/pharmacodynamic targets with consequently therapeutic failure and development of bacterial resistance. [3][4][5][6][7][8][9][10][11][12] Although the impact of ARC has been extensively described in ICU patients, less attention is paid to this in non-ICU patients. 4,6,13 Recently, we documented the prevalence of ARC based on a measured (by 8-hour urinary collection) creatinine clearance (CrCl 8h ) in 232 non-ICU trauma and abdominal surgery patients.…”

Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients

“…Some authors suggested that continuous administration of a drug with a specific nomogram should be used to diminish the time to achieve adequate vanco levels in critically ill patients. (19) Caution has been suggested when using continuous vanco infusions in obese patients, as lower maintenance doses seem to be necessary. (20) …”