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- Kristoffersson, Anders N., 1985-, et al.
(författare)
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Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria
- 2020
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:12, s. 1644-1650
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death.METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis.RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen.DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.
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- Degbey, William Y., et al.
(författare)
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Customers driving a firm's responsible innovation response for grand challenges : A co-active issue-selling perspective
- 2024
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Ingår i: The Journal of product innovation management. - : John Wiley & Sons. - 0737-6782 .- 1540-5885. ; 41:2, s. 379-402
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Tidskriftsartikel (refereegranskat)abstract
- Grand challenges vary across industries and call for firms to craft a responsible innovation response to effectively address them. However, key questions concerning why firms embrace responsible innovation and the process by which they respond to grand challenges have yet to be fully answered. We integrate an issue-selling theoretical lens and the customer role from an innovation perspective to theorize about the different influencing motives that customers exert on their corresponding supplying firm to craft a more responsible innovation response to grand challenges. Based on qualitative data collected in almost a 10-year period from multiple respondents across eight customer firms and two supplying firms, we identify three core motives-regulatory, business opportunity, and socio-environmental motives-that propel customers to influence supplying firms to craft different forms of responsible innovation responses. Our research also reveals three vital socio-human capital pathways-human capital, socio-behavioral, and relationship-which, in turn, foster a co-active engagement in addressing grand challenges innovatively and responsibly. In so doing, this research advances novel theorizing on co-active engagement in responsible innovation where the customer acts as the primary champion and the supplier as the implementer. We discuss the important implications for customers and other stakeholders.
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- Idelevich, E. A., et al.
(författare)
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Microbiological diagnostics of bloodstream infections in Europe-an ESGBIES survey
- 2019
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Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 25:11, s. 1399-1407
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: High-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories.Methods: We performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries.Results: Responses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC.Conclusions: Laboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.
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