Background and objectives Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of b-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT.Design, setting, participants, & measurements We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one-and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 mg/ml for .50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate.Results Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with #45% target attainment, whereas 12 g/d was associated with $95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion.Conclusions Extended infusions of piperacillin-tazobactam are associated with greater probability of target attainment in patients receiving continuous RRT.

Previous studies have identified laboratory markers for severe Clostridium difficile infection (CDI). The most consistent of these markers is the presence of marked leukocytosis. We examined the validity of these markers as predictors of mortality in patients with CDI. We excluded patients with preexisting hematologic conditions that would be expected to impair their ability to demonstrate leukocytosis. On univariate analysis, marked leukocytosis (P = 0.02), thrombocytopenia (P = 0.008), and increased blood urea nitrogen (P < 0.001) and creatinine (P = 0.001) levels were found to be significantly associated with mortality in patients with CDI. However, on logistic regression analysis, only renal impairment was found to be an independent predictor (odds ratio, 5.07). Importantly, in our study, leukocytosis was not an independent predictor after adjustment for other variables, which may be due to our selection criteria when adjusting for confounding variables. We are therefore of the opinion that in immunocompromised hosts who are leukopenic at the time of CDI diagnosis, other laboratory markers should be identified to serve as indicators for severe disease.

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Clostridium difficile infection (CDI) has emerged as a problem of epidemic proportions. Previous exposure to broad-spectrum antibiotics remains the most important predisposing factor for the disease. However, PPIs are increasingly being overprescribed and recent research has, therefore, focused on the association between PPI therapy and CDI. While the data remain observational, increasing evidence exists for at least a modest association between PPI use and CDI.

: Our results support the conclusion of preceding studies that leukocytosis, thrombocytosis, and hypoalbuminemia are reliable clinical predictors for CDAD even after careful exclusion of confounding factors.