Background We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy. Methods This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality. Results Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118–.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021–9.202]). Conclusions Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy. Clinical Trials Registration NCT01732250
patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26e1.04) or 14-day mortality (aOR1.09, 95% CI 0.60e1.96). Discussion: In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.
Objectives: The rise in carbapenem resistance among Gram-negative bacteria has renewed interest in colistin. Recently, the EUCAST-CLSI Polymyxin Breakpoints Working Group declared that broth microdilution (BMD) is the only valid method for colistin susceptibility testing. BMD is not easily incorporated into the routine work of clinical laboratories, and usually this test is incorporated serially, resulting in
Objective Biotechnology has promoted the discovery and development of new types of therapeutical agents for use in humans: biotech drugs offer innovative, targeted therapies with enormous potential to address unmet medical needs of patients with cancer, AIDS and other serious diseases. However, the therapeutic application of these novel therapies poses serious problems concerning the connection between cost sustainability and innovative value. The aims of the present study are to assess the level of therapeutic innovation of biotech drugs approved by the European Medicines Agency between 2004 and 2011, to make a comparison with the trend of biotech drugs approved between 1995–2003, as previously reported, and to evaluate their economic impact on the Italian healthcare system. Methods The data source used was the European Public Assessment Report (EPAR) of human medicines available on European Medicines Agency (EMA) website. The scores for therapeutic innovation were assigned according to the algorithm created by Motola et al. Drug expenditure data was obtained from Information Management System–Health Italy database. The list of drugs under analysis was downloaded from European Medicines Agency website and information on approved drugs were retrieved from the European Public Assessment Reports as well as from PubMed databank. Results From 2004 to 2011, the European Medicines Agency approved 47 biotech drugs: 43 biopharmaceutical innovators and 4 vaccines. Our analysis involved 33 of the 47 biotech drugs approved: 18 products resulted in important therapeutic innovations, 6 in moderate and 5 in modest therapeutic innovations, 2 in pharmacological innovations and finally, 2 involved only technological innovations. We also evaluated the influence of biotech drugs and their different scores for innovation with regard to expenditure as well as consumption. In 2010 and in 2011, the major part of expenditure and consumption concerned biotech drugs classified as important therapeutic innovations, while moderate, modest, pharmacological and technological innovators revealed very reduced contributions in this regard. Conclusions Our study revealed that 50% of biotech drugs approved between 2004–2011 represented an important or moderate therapeutic innovation. The remaining biotech drugs did not add any extra value in the decision-making process concerning the application of economic strategies in the healthcare field. These considerations suggest decision-makers should optimise application of health technology assessment strategies aimed at evaluating new technologies and sustainable costs in clinical practice.
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