International journal of antimicrobial agents
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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.
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Int. J. Antimicrob. Agents · Dec 2015
ReviewCan procalcitonin monitoring reduce the length of antibiotic treatment in bloodstream infections?
Antibiotic overconsumption and subsequent bacterial multidrug resistance are associated with increased mortality, length of hospitalisation and healthcare costs. Discontinuation of antibiotic treatment in severe infections, such as bloodstream infections (BSIs), is a demanding clinical decision. ⋯ Furthermore, the presented data indicate that PCT assessment is helpful in the diagnosis of infective endocarditis. In conclusion, monitoring of PCT together with evaluation of the clinical situation is a valuable tool in reducing the length of antimicrobial treatment in BSIs.
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The serum procalcitonin (PCT) concentration reflects both the systemic response to bacterial infection and its severity. However, its accuracy in distinguishing intensive care unit (ICU) patients with and without infection remains low owing to a lack of specificity and the time lapse between infection onset and the PCT rise. Hence, PCT cannot be used as a marker to start or withhold antibiotic therapy for ICU patients. ⋯ PCT-guided algorithms to guide antibiotic discontinuation were able to shorten antibiotic duration without impacting patient outcomes in several multicentre randomised studies. Notably, antibiotics can be stopped very early when PCT is low and remains low as this indicates that bacterial infection is unlikely. When PCT falls to <0.5 ng/mL or >80% from its peak value, antibiotics for non-localised infections can safely be stopped.
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Int. J. Antimicrob. Agents · Nov 2015
ReviewA resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens.
β-Lactamase inhibitors (BLIs) have played an important role in combatting β-lactam resistance in Gram-negative bacteria, but their effectiveness has diminished with the evolution of diverse and deleterious varieties of β-lactamases. In this review, a new generation of BLIs and inhibitor combinations is presented, describing epidemiological information, pharmacodynamic studies, resistance identification and current clinical status. Novel serine BLIs of major interest include the non-β-lactams of the diazabicyclo[3.2.1]octanone (DBO) series. ⋯ Although effective inhibitor combinations are in development for the treatment of infections caused by Gram-negative bacteria with serine carbapenemases, better options are still necessary for pathogens that produce metallo-β-lactamases (MBLs). The aztreonam/avibactam combination demonstrates inhibitory activity against MBL-producing enteric bacteria owing to the stability of the monobactam to these enzymes, but resistance is still an issue for MBL-producing non-fermentative bacteria. Because all of the inhibitor combinations are being developed as parenteral drugs, an orally bioavailable combination would also be of interest.