ABSTRACT
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 ß-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 µg/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.
Subject(s)
Acute Kidney Injury/therapy , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Penicillanic Acid/analogs & derivatives , Acute Kidney Injury/microbiology , Adult , Aged , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacokinetics , Bacterial Infections/complications , Critical Illness , Dialysis Solutions/chemistry , Female , Hemodiafiltration , Humans , Infusions, Intravenous , Male , Middle Aged , Penicillanic Acid/administration & dosage , Penicillanic Acid/blood , Penicillanic Acid/pharmacokinetics , Piperacillin/administration & dosage , Piperacillin/blood , Piperacillin/pharmacokinetics , Piperacillin, Tazobactam Drug Combination , Time FactorsSubject(s)
Anti-Bacterial Agents/pharmacokinetics , Ciprofloxacin/pharmacokinetics , Critical Illness , Renal Dialysis/methods , Aged , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/therapeutic use , Area Under Curve , Bacterial Infections/drug therapy , Bacterial Infections/mortality , Ciprofloxacin/blood , Ciprofloxacin/therapeutic use , Critical Illness/mortality , Dose-Response Relationship, Drug , Drug Resistance, Microbial , Female , Humans , Male , Metabolic Clearance Rate , Microbial Sensitivity Tests , Middle Aged , Prospective StudiesABSTRACT
PURPOSE: : Recent research has recognized surrogate markers for Clostridium difficile-associated diarrhea (CDAD). Among the most consistently identified markers are the leukocyte count, platelet count, and albumin level. Previous investigators failed to exclude patients with hematologic disorders that may have confounded their results. Therefore, the exclusion of this subset from our study lends it a unique perspective. METHODS: : We undertook a retrospective review of inpatients at our institution that were diagnosed with nosocomial diarrhea and subsequently had a stool sample sent for C. difficile toxins A and B. Patients with major hematologic disorders were excluded. RESULTS: : A total of 77 C. difficile-positive patients and 91 C. difficile-negative patients were studied. Patients with CDAD had a significantly higher leukocyte and platelet count but a lower albumin level compared with patients without CDAD. CONCLUSION: : 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.