Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study

Abstract

BackgroundAugmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).MethodsIn this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.ResultsDuring the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.ConclusionsHigher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.

Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT)

“…In view of the fact that target attainment is observed in only about 60-65% of critically ill patients receiving antibiotics and considering the increasing resistance to antibiotics worldwide, higher dosing in these patients could be an alternative strategy to obtain better target attainment when TDM is not available. Carrie et al showed that, in critically ill patients with ARC, higher than licensed dosing regimens of beta-lactam antibiotics may be safe and effective in reducing the rate of therapeutic failure [47]. Moreover, Imani et al found that prescribed daily antibiotic dose ≥ 1.5 times the product information recommendations was associated with better target attainment [26].…”

Effect of augmented renal clearance on the therapeutic drug monitoring of vancomycin in patients after neurosurgery

“…The difference is mainly attributable to the different definitions of ARC and possible differences in patient selection, such as the inclusion or exclusion of patients with renal impairment. 6 Among patients undergoing neurosurgery, the incidence of ARC varies by disease, complications, the time course of treatment, and other factors. Considering the relatively high incidence of ARC, it might influence the pharmacokinetics of drugs, especially those excreted through the kidneys such as vancomycin.…”

Endotoxemia-Induced Release of Pro-inflammatory Mediators Are Associated With Increased Glomerular Filtration Rate in Humans in vivo

“…Renal hyperfiltration is now increasingly being recognized as a clinical entity ( 16 – 18 ). A highly relevant clinical consequence is the augmented clearance of renally excreted drugs, most notably antibiotics, which is important for daily practice as well as for clinical trials investigating novel therapeutic compounds ( 19 – 21 ). Adjustment of the dosing of these drugs should be considered when GFR is increased, as is already common practice when the GFR is decreased ( 22 ).…”