International journal of antimicrobial agents
-
Int. J. Antimicrob. Agents · Feb 2015
Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration.
Fluconazole is a widely used antifungal agent in critically ill patients. It is predominantly (60-80%) excreted unchanged in urine. Sustained low-efficiency diafiltration (SLED-f) is increasingly being utilised in critically ill patients because of its practical advantages over continuous renal replacement therapy. ⋯ CL and AUC0-24 were comparable with previous observations in a pre-dilution mode of continuous venovenous haemodiafiltration. The observed rebound concentration of fluconazole post SLED-f was <2%. Although a definitive dosing recommendation is not possible due to the small patient number, it is clear that doses >200mg daily are likely to be required to achieve the PK/PD target for common pathogens because of significant fluconazole clearance by SLED-f.
-
Int. J. Antimicrob. Agents · Jan 2015
Randomized Controlled TrialPharmacokinetics of meropenem in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration.
The objective of this study was to describe the pharmacokinetics of meropenem, administered by continuous infusion (CI) or intermittent bolus (IB), in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and to evaluate the frequency of pharmacokinetic/pharmacodynamic target attainment with each dosing strategy. This was a prospective, randomised controlled trial in critically ill patients receiving CVVH and administered meropenem by CI or IB. Serial meropenem concentrations in plasma and ultrafiltrate were measured after administration of a standard total daily dose (4 g/day on Day 1, followed by 3g/day thereafter) on two occasions during antibiotic therapy. ⋯ CVVH contributed to ca. 50% of meropenem total clearance in these patients. The administered meropenem doses resulted in plasma drug concentrations that were >4× the targeted susceptibility breakpoint (2mg/L) for 100% of the dosing interval, for both groups, on both occasions. CI could be an alternative to IB for meropenem administration in critically ill patients receiving CVVH.
-
Int. J. Antimicrob. Agents · Jan 2015
First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients.
The primary objective of this study was to determine the volume of distribution (Vd) (L/kg) of intravenous aminoglycosides (AGs) in critically ill haematological malignancy patients. Secondary objectives were to determine the body weight (actual, ideal, adjusted or lean) that yields the most precise estimate of Vd when normalised in L/kg as well as the frequency that current first-dose strategies result in post-distributional peak concentrations (C(peak)) within the target range (tobramycin 16-24 mg/L; amikacin 32-48 mg/L). In total, 58 AG doses were included (tobramycin, n = 34; amikacin, n = 24). ⋯ Target C(peak) (tobramycin 20mg/L; amikacin 40 mg/L) was achieved in only 25% of all AG episodes, with 4% exceeding the target and 71% falling below the target. Twenty-four organisms were isolated in the study sample; target C(peak) achievement (tobramycin 20 mg/L; amikacin 40 mg/L) would yield a peak:minimum inhibitory concentration of 10 in 75% and 52% of organisms, respectively. In conclusion, an increased Vd of AGs was identified in this critically ill haematological malignancy patient sample, and current dosing yielded a suboptimal C(peak) in the majority of patients.
-
Int. J. Antimicrob. Agents · Dec 2014
Review Meta AnalysisColistin for the treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: a systematic review and meta-analysis.
Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) has emerged as an important and intractable clinical problem. This review assessed the efficacy and safety of colistin for treatment of MDR GNB VAP. PubMed and Embase were searched for controlled studies of colistin for treatment of MDR GNB VAP. ⋯ Colistin appears as effective and safe as β-lactam antibiotics for the treatment of MDR GNB VAP. AS colistin may be a beneficial adjunct to IV colistin in the management of MDR GNB VAP. Colistin combined therapy does not appear to provide better outcomes compared with colistin monotherapy.