International journal of antimicrobial agents
-
Int. J. Antimicrob. Agents · Apr 2015
Observational StudyAugmented renal clearance, low β-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study.
Whilst augmented renal clearance (ARC) is associated with reduced β-lactam plasma concentrations, its impact on clinical outcomes is unclear. This single-centre prospective, observational, cohort study included non-pregnant, critically ill patients aged 18-60 years with presumed severe infection treated with imipenem, meropenem, piperacillin/tazobactam or cefepime and with creatinine clearance (CL(Cr)) ≥60 mL/min. Peak, intermediate and trough levels of β-lactams were drawn on Days 1-3 and 5. ⋯ A link between ARC and clinical failure (18/98; 18%) was not observed. ARC and subthreshold β-lactam antibiotic concentrations were widespread but were not associated with clinical failure. Larger studies are necessary to determine whether standard dosing regimens in the presence of ARC impact negatively on clinical outcome and antibiotic resistance.
-
Int. J. Antimicrob. Agents · Apr 2015
Editorial CommentAugmented renal clearance and therapeutic monitoring of β-lactams.
Successful application of antibacterial therapy in the critically ill requires an appreciation of the complex interaction between the host, the causative pathogen and the chosen pharmaceutical. A pathophysiological change in the intensive care unit (ICU) patient challenging the 'one dose fits all' concept includes augmented renal clearance (ARC), defined as a creatinine clearance (CL(Cr)) of ≥130 mL/min. ⋯ One way to document and alter drug levels is via therapeutic drug monitoring (TDM). The interactions of ARC and β-lactam TDM are further explored in this article in specific reference to a concomitant article in this issue of the journal.
-
Int. J. Antimicrob. Agents · Mar 2015
β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study.
Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of β-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. ⋯ The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these β-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.
-
Int. J. Antimicrob. Agents · Mar 2015
ReviewInhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: A systematic review.
We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. ⋯ Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.
-
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.