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      International Consensus Guidelines for the Optimal Use of the Polymyxins : Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious D

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          The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.

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          Most cited references137

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          Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections.

          Increasing multidrug resistance in Gram-negative bacteria, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, presents a critical problem. Limited therapeutic options have forced infectious disease clinicians and microbiologists to reappraise the clinical application of colistin, a polymyxin antibiotic discovered more than 50 years ago. We summarise recent progress in understanding the complex chemistry, pharmacokinetics, and pharmacodynamics of colistin, the interplay between these three aspects, and their effect on the clinical use of this important antibiotic. Recent clinical findings are reviewed, focusing on evaluation of efficacy, emerging resistance, potential toxicities, and combination therapy. In the battle against rapidly emerging bacterial resistance we can no longer rely entirely on the discovery of new antibiotics; we must also pursue rational approaches to the use of older antibiotics such as colistin.
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            Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.

            Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries. Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23). Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
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              Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial


                Author and article information

                Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
                January 2019
                January 2019
                February 02 2019
                : 39
                : 1
                : 10-39
                [1 ]School of Pharmacy and Pharmaceutical Sciences; University at Buffalo; State University of New York; Buffalo New York
                [2 ]Detroit Medical Center; Detroit Michigan
                [3 ]Department of Internal Medicine; Medical School; Universidade Federal, do Rio Grande do Sul; Porto Alegre Brazil
                [4 ]Infectious Diseases Service; Hospital de Clínicas de Porto Alegre; Porto Alegre Brazil
                [5 ]Infectious Diseases Institute; Rambam Health Care Campus; Haifa Israel
                [6 ]The Ruth and Bruce Rappaport Faculty of Medicine; Technion; Israel Institute of Technology; Haifa Israel
                [7 ]First Department of Propaedeutic Medicine; Laikon Hospital; Medical School; National and Kapodistrian University of Athens; Athens Greece
                [8 ]Eshelman School of Pharmacy; University of North Carolina at Chapel Hill; Chapel Hill North Carolina
                [9 ]Infectious Diseases Unit; Ospedale Policlinico San Martino-Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia; Genoa Italy
                [10 ]Department of Health Sciences; University of Genoa; Genoa Italy
                [11 ]1st Department of Internal Medicine, Infectious Diseases; Hygeia General Hospital; Athens Greece
                [12 ]Drexel University College of Medicine; Philadelphia Pennsylvania
                [13 ]Department of Medical Microbiology and Infectious Diseases; Erasmus MC; Rotterdam The Netherlands
                [14 ]University of Houston College of Pharmacy; Houston Texas
                [15 ]Division of Infectious Diseases and Tropical Medicine; Department of Medicine; Faculty of Medicine Siriraj Hospital; Mahidol University; Bangkok Thailand
                [16 ]Division of Pulmonary and Critical Care; Department of Medicine; Northwestern University Feinberg School of Medicine; Chicago Illinois
                [17 ]Department of Microbiology; Monash Biomedicine Discovery Institute; Monash University; Clayton Victoria Australia
                [18 ]Drug Delivery, Disposition and Dynamics; Monash Institute of Pharmaceutical Sciences; Monash University; Parkville Victoria Australia
                [19 ]Division of Infectious Diseases; University of Michigan Medical School; Ann Arbor Michigan
                © 2019





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