International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Feb 2016
Impact of CYP2C19 genetic polymorphisms on voriconazole dosing and exposure in adult patients with invasive fungal infections.
Voriconazole (VCZ) use is limited by its narrow therapeutic range and significant interpatient variability in exposure. This study aimed to assess (i) the impact of CYP2C19 genotype on VCZ exposure and (ii) the doses required to achieve the therapeutic range in adult patients with invasive fungal infections (IFIs). Therapeutic drug monitoring (TDM) of VCZ, based on trough concentration measurement, and CYP2C19 genotyping were used to guide VCZ dosing in Caucasian patients with IFIs. ⋯ Indices of exposure for CYP2C19*2 carriers were in line with the functional effect of this polymorphism compared with CYP2C19*1/*1 individuals, however comparisons of doses required to achieve target concentrations were not statistically different. The CYP2C19*17 allele predicted both VCZ exposure and dose required to achieve effective and non-toxic concentrations. CYP2C19 genotyping appears useful to guide VCZ initial dosing when coupled with TDM and to explain subtherapeutic concentrations frequently observed in clinical practice.
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Int. J. Antimicrob. Agents · Dec 2015
The Thuringian registry for bloodstream infections, antibiotic resistance and the practice of blood culture sampling-AlertsNet.
Evidence-based blood culture (BC) testing is of utmost importance for intensive care unit (ICU) patients suspected for sepsis. Knowledge of the aetiological agent and its susceptibility to anti-infective agents enables the clinician to initiate appropriate antimicrobial therapy and guides diagnostic procedures. This has been shown to reduce mortality, ICU stay and antibiotic overuse. ⋯ A population-based survey on BC practice has been established for the German Federal State of Thuringia connecting both hospitals and microbiological laboratories within an electronic registry for immediate enrolment of BC findings (AlertsNet; http://www.alertsnet.de). The registry includes microbiological results and clinical data as well as institutional variables (e.g. case severity indices) from all patients with clinically relevant positive BCs at the participating centres. The main objectives are to sustain and expand a population-based surveillance and warning system for the assessment of diagnosis, risk factors, treatment and outcomes of hospitalised patients and to improve outcomes of patients with bloodstream infections.
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Int. J. Antimicrob. Agents · Dec 2015
Review Meta AnalysisIntravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of pneumonia caused by multidrug-resistant pathogens: a systematic review and meta-analysis.
Colistin has been used to treat nosocomial pneumonia (NP) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) via different administration routes. Whether patients may benefit from aerosolised colistin as adjunctive treatment was contradictory. We aimed to clarify the safety and efficacy of administering aerosolised and intravenous (IV-AS) colistin versus intravenous (IV) colistin alone in patients with NP caused by MDR-GNB. ⋯ Nephrotoxicity did not differ significantly between IV-AS and IV groups (five studies; 383 patients) (OR=1.11, 95% CI 0.69-1.80; P=0.67). These data indicate that IV-AS colistin has additional benefits compared with IV colistin alone. Clinicians should be encouraged to give combined administration routes in critically ill patients with NP caused by MDR-GNB.
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Int. J. Antimicrob. Agents · Dec 2015
ReviewCan procalcitonin levels indicate the need for adjunctive therapies in sepsis?
After decades of extensive experimental and clinical research, septic shock and the related multiple organ dysfunction still remain the leading cause of mortality in intensive care units (ICUs) worldwide. Defining sepsis is a difficult task, but what is even more challenging is differentiating infection-induced from non-infection-induced systemic inflammatory response-related multiple organ dysfunction. As conventional signs of infection are often unreliable in intensive care, biomarkers are used, of which one of the most frequently investigated is procalcitonin. ⋯ A relatively new potential approach could be attenuation of the overwhelming cytokine storm by specific cytokine adsorbents. Both interventions have been applied in daily practice on a large scale, with firm pathophysiological rationale but weak evidence supported by clinical trials. The purpose of this review is to give an overview on the pathophysiology of sepsis as well as the role and interpretation of biomarkers and their potential use in assisting adjunctive therapies in sepsis in the future.
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Int. J. Antimicrob. Agents · Dec 2015
ReviewEndogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies.
The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. ⋯ The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach.