International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Dec 2010
ReviewWhat is the pathophysiology of the septic host upon admission?
The enormous case-fatality rate of severe sepsis and septic shock has resulted in considerable efforts being made towards understanding their complex mechanisms of pathogenesis. This has been done with the hope that agents that interfere with the pathways of pathogenesis and modulate the immune response of the host may be candidates for therapy. Disappointing results from most trials of immunomodulators in sepsis have led to understanding that the progression of patients to multiple organ dysfunction syndrome involves blunting of the pro-inflammatory cytokine storm. ⋯ Recent data from the Hellenic Sepsis Study Group demonstrate that components of CARS upon transition from sepsis to severe sepsis/shock differ in relation to the underlying type of infection. These data underscore that the pathogenesis of sepsis presents considerable heterogeneity from one patient to another. That heterogeneity should be taken into consideration when deciding to administer an immunomodulator.
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Int. J. Antimicrob. Agents · Dec 2010
ReviewNew perspectives on immunomodulatory therapy for bacteraemia and sepsis.
Systemic immune dysregulation is generally acknowledged to be the fundamental molecular mechanism that underlies the pathophysiology of severe sepsis and septic shock. In the presence of a systemic infection, microbial pathogens and their soluble mediators induce generalised immune activation and coagulation activation, leading to severe sepsis and septic shock. For decades, immune-based therapies have been devised with the specific intent of inhibiting the pro-inflammatory events that are thought to precipitate the septic process. ⋯ Candidiasis, cytomegalovirus activation and secondary infections by relatively avirulent bacterial pathogens such as Stenotrophomonas and Acinetobacter spp. are commonplace in septic patients during prolonged Intensive Care Unit stays. Immunological tools to detect sepsis-induced immunosuppression are now available, and novel immunoadjuvants are in development to re-establish immune competence in sepsis patients. The intelligent use of immunomodulatory agents in sepsis will necessitate a personalised medicine approach to treat each patient at the appropriate time and with the optimal therapy.
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Int. J. Antimicrob. Agents · Dec 2010
ReviewCatheter-related bloodstream infections: catheter management according to pathogen.
Central-line access is an essential part of modern healthcare practice; however, catheter-related bloodstream infection is a major problem that causes substantial morbidity and mortality, and excess length of stay and cost. The risk of infection depends on the type of device, the site of insertion, the underlying conditions and the appropriate prevention measures taken during catheter insertion. Management of catheter-related bloodstream infection involves deciding on catheter removal, antimicrobial catheter lock solution and the type and duration of systemic antimicrobial therapy. ⋯ The decision regarding whether the catheter should be removed or retained is therefore crucial. One of the major factors to be considered is the type of organism involved in the catheter-related infection. This review outlines the epidemiology, pathogenesis, diagnosis, microbiology and management of catheter-related infections, mainly focusing on the management of the intravascular device according to the pathogen.
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The emergence of antibiotic resistance in bacterial pathogens is an inevitable consequence of antibiotic use. Despite repeated warnings, negligent antibiotic use and poor infection-control practice have led to the continuing development of extensive resistance problems worldwide. ⋯ Effective national and international programmes of control to combat these problems are urgently needed. The potential for success of such coordinated efforts has been demonstrated by the recent dramatic reductions in MRSA and C. difficile infections in England.
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Int. J. Antimicrob. Agents · Nov 2010
ReviewOritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains.
Oritavancin is a lipoglycopeptide antibiotic under investigation for the treatment of serious infections caused by Gram-positive bacteria. Oritavancin has demonstrated rapid dose-dependent bactericidal activity towards vancomycin-susceptible and -resistant enterococci, meticillin-susceptible and -resistant Staphylococcus aureus, vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), vancomycin-resistant S. aureus (VRSA) and small-colony variants of S. aureus. It is also active against Clostridium difficile. ⋯ So far, oritavancin has demonstrated efficacy in two pivotal Phase III trials conducted in patients with complicated skin and skin-structure infections in which oritavancin was compared with vancomycin plus cefalexin. In both trials, the primary endpoint (clinical cure in clinically evaluable patients at first follow-up with a 10% non-inferiority margin) was met, with the advantages of shorter duration of therapy and fewer adverse events. Further results indicating its activity against bacteria growing in biofilms as well as stationary-phase bacteria open the way for its use to treat prosthetic device infections, which is to be investigated in upcoming trials.