Background Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment. Methods This prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MICECOFF and ƒT > 4×MICECOFF) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes. Results A total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MICECOFF and 36.7% achieved 100%ƒT > 4×MICECOFF. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival. Conclusions Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients. Trial registration Netherlands Trial Registry (EXPAT trial), NTR 5632. Registered on 7 December 2015.

Identification of implementation barriers for adherence to guidelines pertaining to delirium is feasible with a survey. Results of this study may help to design-targeted implementation strategies for ICU delirium management.

Purpose To develop and validate a population pharmacokinetic model of ciprofloxacin intravenously in critically ill patients, and determine target attainment to provide guidance for more effective regimens. Methods Non-linear mixed-effects modelling was used for the model development and covariate analysis. Target attainment of an ƒAUC 0-24 /MIC ≥ 100 for different MICs was calculated for standard dosing regimens. Monte Carlo simulations were performed to define the probability of target attainment (PTA) of several dosing regimens. Results A total of 204 blood samples were collected from 42 ICU patients treated with ciprofloxacin 400-1200 mg/day, with median values for age of 66 years, APACHE II score of 22, BMI of 26 kg/m 2 , and eGFR of 58.5 mL/min/1.73 m 2. The median ƒAUC 0-24 and ƒC max were 29.9 mg•h/L and 3.1 mg/L, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model. We did not find any significant covariate to add to the structural model. The proportion of patients achieving the target ƒAUC 0-24 /MIC ≥ 100 were 61.9% and 16.7% with MICs of 0.25 and 0.5 mg/L, respectively. Results of the PTA simulations suggest that a dose of ≥ 1200 mg/day is needed to achieve sufficient ƒAUC 0-24 /MIC ratios. Conclusions The model described the pharmacokinetics of ciprofloxacin in ICU patients adequately. No significant covariates were found and high inter-individual variability of ciprofloxacin pharmacokinetics in ICU patients was observed. The poor target attainment supports the use of higher doses such as 1200 mg/day in critically ill patients, while the variability of inter-individual pharmacokinetics parameters emphasizes the need for therapeutic drug monitoring to ensure optimal exposure.

The intervention increased hardcore smokers' receptivity to information about smoking cessation and decreased their cigarette consumption by about 1 cigarette per day. Although the results are positive, the clinical relevance may be limited. We recommend further developing this intervention for practical use in health care settings. Statement of contribution What is already known on this subject? Hardcore smokers have smoked for many years and do not intend to quit. There are currently no online interventions for hardcore smokers. What does this study add? This study tested an online intervention for hardcore smokers. The intervention increased hardcore smokers' receptivity to information about quitting. It also helped to reduce the number of cigarettes per day.

Purpose Failed conversion of epidural labor analgesia (ELA) to epidural surgical anesthesia (ESA) for intrapartum Cesarean delivery (CD) has been observed in clinical practice. However, spinal anesthesia (SA) in parturients experiencing failed conversion of ELA to ESA has been associated with an increased incidence of serious side effects. In this retrospective cohort analysis, we examined our routine clinical practice of removing the in situ epidural, rather than attempting to convert to ESA, prior to administering SA for intrapartum CD. Methods Hemodynamic data, frequencies of either high or total spinal block, and maternal and neonatal outcome data were gathered from the anesthesia records of all parturients at the Amphia Hospital, undergoing intrapartum CD between January 1, 2001 and May 1, 2005. Results Complete data were available for 693 patients (97.6%) of the 710 medical records that were identified. Of the 693 patients, 508 (73.3%) had no ELA and received SA, 128 patients (18.5%) received SA following epidural anesthesia for labor, 19 (2.7%) underwent conversion of ELA to ESA, and 38 (5.5%) received general anesthesia. When comparing both SA groups, no clinically relevant differences were observed regarding the incidence of total spinal block (0% in both groups) or high spinal block (0.2 vs 0.8%, P = 0.36). The number of hypotensive episodes, the total amount of ephedrine administered, and the Apgar scores recorded at 5 and 10 min were similar amongst groups. Conclusions The incidence of serious side effects associated with SA for intrapartum CD following ELA is low and not different compared to SA only. RésuméObjectif Dans la pratique clinique, l'e´chec du passage d'une analge´sie pe´ridurale pour le travail obste´trical a`une anesthe´sie pe´ridurale chirurgicale pour un accouchement par ce´sarienne a e´te´observe´. Cependant, la rachianesthe´sie re´alise´e chez les parturientes chez qui la conversion de la pe´ridurale avait e´choue´a e´te´associe´e à une incidence accrue d'effets secondaires graves. Dans cette analyse de cohorte re´trospective, nous avons examineń otre pratique clinique habituelle, qui consistait a`retirer le cathe´ter pe´ridural avant de re´aliser une rachianesthe´sie pour un accouchement par ce´sarienne, plutôt que de tenter une conversion de la pe´ridurale.