International journal of antimicrobial agents
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Severe sepsis and septic shock are lethal complications of infection, characterised by dysregulated inflammatory and immune responses. Our understanding of the pathogenesis of sepsis has improved markedly in recent years, but unfortunately has not been translated into efficient treatment strategies. Epigenetic mechanisms such as covalent modification of histones by acetylation are master regulators of gene expression under physiological and pathological conditions, and strongly impact on inflammatory and host defence responses. ⋯ Strikingly, proof-of-principle studies demonstrated that HDACi protect from lethal toxic shock and septic shock. Overall, our observations argue for a close monitoring of the immunological and infection status of patients treated with HDACi, especially immunocompromised cancer patients. They also support the concept of pharmacological inhibitors of HDACs as promising drugs to treat inflammatory diseases, including sepsis.
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Int. J. Antimicrob. Agents · Jun 2013
ReviewAntimicrobial resistance: action to combat the rising microbial challenges.
Antimicrobial therapy transformed medical practice from a merely diagnosis-focused approach 80 years ago to a treatment-focused approach, saving millions of lives in the years to follow. Today, numerous medical advances made possible by effective antibiotics are being threatened by the relentlessly rising rates of bacteria resistant to all currently available antibiotics. This phenomenon is a consequence of antibiotic misuse, which exerts undue selective pressure on micro-organisms, combined with defective infection control practices that accelerate their spread. ⋯ It should include actions aiming at optimising antibiotic use, strengthening surveillance and infection control, and improving healthcare worker and public education with regard to antibiotics. Research efforts to bring new effective antibiotics to patients need to be fostered in order to negate the consequences of the current lack of antimicrobial therapy options. A holistic view of AMR as well as intersectoral collaboration between human and veterinary medicine is required to best address the problem.
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Int. J. Antimicrob. Agents · Jun 2013
Management of candidaemia and invasive candidiasis in critically ill patients.
Critically ill patients in the intensive care unit (ICU) are at increased risk of encountering bloodstream infections (BSIs) with Candida spp., associated with an elevated crude mortality rate. This supports the significance of early detection of infection and identification of the most effective management approach. A review of the various antifungal treatments and an evaluation of the diverse management approaches for invasive candidiasis in critically ill patients is necessary for guiding evidence-based decision-making. ⋯ This paper summarises the most recent literature as well as the guidelines issued by the Infectious Diseases Society of America. The objective is to identify the best diagnosis and management approaches for serious Candida infections in critically ill patients. In addition, this article addresses an important aspect associated with managing candidaemia in critically ill patients pertaining to the decision for intravenous catheter removal.
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Int. J. Antimicrob. Agents · Jun 2013
Can population pharmacokinetic modelling guide vancomycin dosing during continuous renal replacement therapy in critically ill patients?
Treatment of resistant bacteria such as meticillin-resistant Staphylococcus aureus (MRSA) relies on achieving adequate antibiotic concentrations at the site of infection. Strategies to attain such targets in septic critically ill patients receiving renal replacement therapy (RRT) are uncommon but could be useful for increasing the likelihood of therapeutic dosing. The aim of this study was to conduct a population pharmacokinetic (PK) analysis in septic patients undergoing continuous RRT and to determine which parameters were associated with inadequate vancomycin concentrations. ⋯ When covariates were tested, none were found to adequately explain changing vancomycin CL or Vd in the population PK model. In particular, the lack of correlation between CL and RRT settings was likely due to the multiple confounders known to influence antibiotic prescription in this setting. These data provide a cautionary tale of the challenges of describing pharmacokinetics in critically ill patients receiving RRT and highlights the need for a detailed, prospective, multicentre study to better inform dosing practice.