International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Dec 2010
ReviewMultidrug-resistant Gram-negative bacteria: how to treat and for how long.
The emergence of multidrug-resistant (MDR) Gram-negative bacilli creates a big problem for the treatment of nosocomial infections. As the pharmaceutical pipeline wanes, the only therapeutic options are two revived antibacterials (colistin and fosfomycin), a newer one (tigecycline) and an early-phase neoglycoside (ACHN-490). Polymyxins, known since 1947, are mostly represented by polymyxin E (colistin), which has recently gained a principal position in the management of the most difficult-to-treat MDR Gram-negative pathogens -Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. ⋯ However, dosage adjustment is required because of low blood levels. ACHN-490, which has promising in vitro activity against MDR K. pneumoniae, is still in early phase II trials in urinary tract infections. Meanwhile, the strict application of infection control measures is the cornerstone of nosocomial infection prevention, and antibiotic stewardship, exemplified by appropriate duration of therapy and de-escalation policies, should not be overlooked.
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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
Comparative StudyEfficacy of daptomycin combined with rifampicin for the treatment of experimental meticillin-resistant Staphylococcus aureus (MRSA) acute osteomyelitis.
Daptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). Daptomycin in combination with rifampicin needs to be assessed in bone infection. An MRSA acute osteomyelitis model was used. ⋯ Vancomycin and daptomycin as single therapies were ineffective, but both combinations were significantly more effective than the corresponding monotherapy. Combination of daptomycin and rifampicin could prevent S. aureus from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage.