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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The use of biomarkers might help to avoid antibiotic misuse and overuse and to curb the rising incidence of microbial resistance. Amongst >100 biomarkers proposed for use as infection/sepsis markers, procalcitonin is the most frequently evaluated. It has been tested in 11 randomised controlled trials with more than 3500 patients and resulted in a considerable 35-70% reduction in antibiotic use without an apparent negative impact on patient outcome. ⋯ There are, however, concerns - trials designed to show non-inferiority of procalcitonin to standard management allowed rather large differences for mortality rates, in the range of 7.5-10%, thus clinically relevant excess mortality by procalcitonin-guided antibiotic therapy cannot be completely ruled out. Marker panels derived from transcriptomic or proteomic profiling hold promise in overcoming the limitations of procalcitonin for differentiating non-infectious from infection-associated inflammation. However, the utility of these novel diagnostic tools in the clinical setting remains to be proven.
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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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Int. J. Antimicrob. Agents · Dec 2010
In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains isolated from the lower respiratory tract of Intensive Care Unit patients with nosocomial pneumonia and receiving antipseudomonal therapy.
Pseudomonas aeruginosa causes severe nosocomial pneumonia in Intensive Care Unit (ICU) patients, with an increased prevalence of multiresistant strains. We examined the impact of the use of antipseudomonal antibiotic(s) on the susceptibility of P. aeruginosa isolated from ICU patients with clinically suspected hospital-acquired pneumonia collected in five teaching hospitals (110 non-duplicate initial isolates; 62 clonal pairs of initial and last isolates during treatment). Minimum inhibitory concentrations (MICs) were determined for amikacin, ciprofloxacin, meropenem, piperacillin/tazobactam (TZP), cefepime and ceftazidime (used in therapy) as well as five reporter antibiotics (aztreonam, colistin, gentamicin, piperacillin and ticarcillin) using Clinical and Laboratory Standards Institute (CLSI) methodology. ⋯ There was a significant correlation between the use of antibiotics (adjusted for respective proportional use of each drug) and loss of susceptibility at the population level when using EUCAST breakpoints. The high level of resistance of P. aeruginosa in ICU patients with nosocomial pneumonia as well as its further increase during treatment severely narrows the already limited therapeutic options. Further observational studies and the development of early diagnosis for resistant isolates are warranted.