Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Nov 2015
Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children.
The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. ⋯ All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.
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Antimicrob. Agents Chemother. · Nov 2015
Role of urine neutrophil gelatinase-associated lipocalin in the early diagnosis of amphotericin B-induced acute kidney injury.
Determination of the neutrophil gelatinase-associated lipocalin (NGAL) level can be used to detect acute kidney injury (AKI) earlier than determination of the serum creatinine (SCr) level in settings such as cardiac surgery, contrast nephropathy, and intensive care units. We hypothesized that urine NGAL (UrNGAL) would be an early biomarker of drug nephrotoxicity. To test this, we studied hemodynamically stable patients treated with amphotericin B (AmB). ⋯ In a patient-level analysis, we found that AKI could be detected 3.2 days earlier by the use of the UrNGAL criterion than by the use of the SCr criterion (times to AKI by the UrNGAL and SCr criteria, 3.7 ± 2.5 versus 6.9 ± 3.3 days, respectively; P = 0.001). Future studies should evaluate if a treatment strategy oriented toward evaluation of UrNGAL levels will improve outcomes. These findings for AmB-induced AKI in leishmaniasis patients could serve as a basis for the investigation of urine biomarkers in the early detection of drug nephrotoxicity in other clinical settings.