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      Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime–Avibactam

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          Abstract

          Background

          The aim of this study was to evaluate the predictive performance of the INCREMENT-CPE (ICS), Pitt bacteremia score (PBS) and qPitt for mortality among patients treated with ceftazidime–avibactam for carbapenem-resistant Enterobacteriaceae (CRE) infections.

          Methods

          Retrospective, multicenter, cohort study of patients with CRE infections treated with ceftazidime–avibactam between 2015 and 2019. The primary outcome was 30-day all-cause mortality. Predictive performance was determined by assessing discrimination, calibration and precision.

          Results

          In total, 109 patients were included. Thirty-day mortality occurred in 18 (16.5%) patients. There were no significant differences in discrimination of the three scores [area under the curve (AUC) ICS 0.7039, 95% CI 0.5848–0.8230, PBS 0.6893, 95% CI 0.5709–0.8076, and qPitt 0.6847, 95% CI 0.5671–0.8023; P > 0.05 all pairwise comparisons]. All scores showed adequate calibration and precision. When dichotomized at the optimal cut-points of 11, 3, and 2 for the ICS, PBS, and qPitt, respectively, all scores had NPV > 90% at the expense of low PPV. Patients in the high-risk groups had a relative risk for mortality of 3.184 (95% CI 1.35–8.930), 3.068 (95% CI 1.094–8.606), and 2.850 (95% CI 1.016–7.994) for the dichotomized ICS, PBS, and qPitt, scores respectively. Treatment-related variables (early active antibiotic therapy, combination antibiotics and renal ceftazidime–avibactam dose adjustment) were not associated with mortality after controlling for the risk scores.

          Conclusions

          In patients treated with ceftazidime–avibactam for CRE infections, mortality risk scores demonstrated variable performance. Modifications to scoring systems to more accurately predict outcomes in the era of novel antibiotics are warranted.

          Electronic supplementary material

          The online version of this article (10.1007/s40121-020-00288-4) contains supplementary material, which is available to authorized users.

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          Most cited references26

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          Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.

          The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model. Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects. We evaluated several variants of split-sample, cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infarction. Random samples with a size between n = 572 and n = 9165 were drawn from a large data set (GUSTO-I; n = 40,830; 2851 deaths) to reflect modeling in data sets with between 5 and 80 events per variable. Independent performance was determined on the remaining subjects. Performance measures included discriminative ability, calibration and overall accuracy. We found that split-sample analyses gave overly pessimistic estimates of performance, with large variability. Cross-validation on 10% of the sample had low bias and low variability, but was not suitable for all performance measures. Internal validity could best be estimated with bootstrapping, which provided stable estimates with low bias. We conclude that split-sample validation is inefficient, and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model.
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            International Consensus Guidelines for the Optimal Use of the Polymyxins

            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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              Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae

              The efficacy of ceftazidime-avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown.
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                Author and article information

                Contributors
                m.rybak@wayne.edu
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                22 February 2020
                22 February 2020
                : 1-14
                Affiliations
                [1 ]GRID grid.254444.7, ISNI 0000 0001 1456 7807, Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, , Wayne State University, ; Detroit, MI USA
                [2 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Clinical Pharmacy, School of Pharmacy, Medication Outcomes Center, , University of California, San Francisco, ; San Francisco, CA USA
                [3 ]GRID grid.265117.6, ISNI 0000 0004 0623 6962, Department of Clinical Sciences, College of Pharmacy, , Touro University California, ; Vallejo, CA USA
                [4 ]GRID grid.414639.d, ISNI 0000 0004 0451 9467, Brooklyn Hospital, ; Brooklyn, NY USA
                [5 ]GRID grid.266515.3, ISNI 0000 0001 2106 0692, Department of Pharmacy Practice, School of Pharmacy, , University of Kansas, ; Kansas City, KS USA
                [6 ]Department of Pharmacy, Lee Health, Fort Myers, FL USA
                [7 ]T2 Biosystems Inc, Lexington, MA USA
                [8 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, , University of Colorado, ; Aurora, CO USA
                [9 ]GRID grid.413103.4, ISNI 0000 0001 2160 8953, Department of Pharmacy, , Henry Ford Hospital, ; Detroit, MI USA
                [10 ]GRID grid.254444.7, ISNI 0000 0001 1456 7807, Department of Medicine, , Wayne State University, ; Detroit, MI USA
                [11 ]GRID grid.413184.b, ISNI 0000 0001 0088 6903, Department of Pharmacy, , Detroit Medical Center, ; Detroit, MI USA
                Article
                288
                10.1007/s40121-020-00288-4
                7223509
                32088843
                e242b56f-8bf7-45bf-a245-f016507d1b10
                © The Author(s) 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 20 December 2019
                Categories
                Original Research

                carbapenem-resistant enterobacteriaceae,ceftazidime–avibactam,increment-cpe,pitt bacteremia

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