International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Feb 2014
ReviewProlonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation.
Given the sparse antibiotic pipeline and the increasing prevalence of resistant organisms, efforts should be made to optimise the pharmacodynamic exposure of currently available agents. Prolonging the infusion duration is a strategy used to increase the percentage of the dosing interval that free drug concentrations remain above the minimum inhibitory concentration (fT>MIC), the pharmacodynamic efficacy driver for time-dependent antibiotics such as β-lactams. β-Lactams, the most commonly prescribed class of antibiotics owing to their efficacy and safety profile, have been the mainstay of therapy since the discovery of penicillin over 60 years ago. ⋯ As a result of these favourable attributes, clinical practice guidelines support the use of prolonged-infusion β-lactams in the treatment of many severe infections. This article discusses the rationale and evidence for prolonging the infusion of β-lactam antibiotics and provides guidance for the implementation of a prolonged-infusion programme.
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Int. J. Antimicrob. Agents · Feb 2014
Area under the concentration-time curve to minimum inhibitory concentration ratio as a predictor of vancomycin treatment outcome in methicillin-resistant Staphylococcus aureus bacteraemia.
There have been few clinical studies on the association between the 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. Patients with MRSA bacteraemia between July 2009 and January 2012 were analysed retrospectively. All adult patients treated with vancomycin for ≥72 h without dialysis were included. ⋯ In the CART analysis, low initial vancomycin AUC24/MIC (<430 by Etest; <398.5 by BMD) was associated with a higher treatment failure rate (50.0% vs. 25.0%, P=0.039 by Etest; 45.0% vs. 23.2%; P=0.065 by BMD). In multivariate analysis, low initial vancomycin AUC24/MIC was a significant risk factor for treatment failure [adjusted odds ratio (aOR)=4.39, 95% confidence interval (CI), 1.26-15.35 by Etest; aOR=3.73, 95% CI 1.10-12.61 by BMD]. In MRSA bacteraemia, a low initial vancomycin AUC24/MIC is an independent risk factor for vancomycin treatment failure.
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Int. J. Antimicrob. Agents · Feb 2014
Activity of linezolid-containing regimens against multidrug-resistant tuberculosis in mice.
The objective of the present study was to compare the activities of regimens containing linezolid (LZD) with those not containing LZD against Mycobacterium tuberculosis infection in mice. The three regimens excluding LZD selected in this study are often used in practice against multidrug-resistant tuberculosis (MDR-TB). ⋯ In particular, when LZD was included in the combination levofloxacin+amikacin+para-aminosalicylic acid+pyrazinamide+clofazimine, culture negativity of the lungs was reached after 2 months of treatment in every case. In addition, the serum levels of interleukin-10 and interferon-γ of mice were determined and were found not to be surrogate markers of bacterial clearance.