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      Development and Validation of a Model to Predict Growth of Potentially Antibiotic-Resistant Gram-Negative Bacilli in Critically Ill Children With Suspected Infection

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          Abstract

          Background

          Risk-based guidelines aid empiric antibiotic selection for critically ill adults with suspected infection with Gram-negative bacilli with high potential for antibiotic resistance (termed high-risk GNRs). Neither evidence-based guidelines for empiric antibiotic selection nor validated risk factors predicting high-risk GNR growth exist for critically ill children. We developed and validated a model for predicting high-risk GNR growth in critically ill children with suspected infection.

          Methods

          This is a retrospective cohort study involving 2 pediatric cohorts admitted to a pediatric intensive care unit (ICU) with suspected infection. We developed a risk model predicting growth of high-risk GNRs using multivariable regression analysis in 1 cohort and validated it in a separate cohort.

          Results

          In our derivation cohort (556 infectious episodes involving 489 patients), we identified the following independent predictors of high-risk GNR growth: hospitalization >48 hours before suspected infection, hospitalization within the past 4 weeks, recent systemic antibiotics, chronic lung disease, residence in a chronic care facility, and prior high-risk GNR growth. The model sensitivity was 96%, the specificity was 48%, performance using the Brier score was good, and the area under the receiver operator characteristic curve (AUROC) was 0.722, indicating good model performance. In our validation cohort (525 episodes in 447 patients), model performance was similar (AUROC, 0.733), indicating stable model performance.

          Conclusions

          Our model predicting high-risk GNR growth in critically ill children demonstrates the high sensitivity needed for ICU antibiotic decisions, good overall predictive capability, and stable performance in 2 separate cohorts. This model could be used to develop risk-based empiric antibiotic guidelines for the pediatric ICU.

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          Most cited references26

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          The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America

          Abstract Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.
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            Executive Summary: Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

            It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
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              Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis.

              Our primary goal was to evaluate the impact on in-hospital mortality rate of adequate empirical antibiotic therapy, after controlling for confounding variables, in a cohort of patients admitted to the intensive care unit (ICU) with sepsis. The impact of adequate empirical antibiotic therapy on early (<3 days), 28-day, and 60-day mortality rates also was assessed. We determined the risk factors for inadequate empirical antibiotic therapy. DESIGN Prospective cohort study. ICU of a tertiary hospital. All the patients meeting criteria for sepsis at admission to the ICU. None. Four hundred and six patients were included. Microbiological documentation of sepsis was obtained in 67% of the patients. At ICU admission, sepsis was present in 105 patients (25.9%), severe sepsis in 116 (28.6%), and septic shock in 185 (45.6%). By multivariate analysis, predictors of in-hospital mortality were Sepsis-related Organ Failure Assessment (SOFA) score at ICU admission (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.19-1.40), the increase in SOFA score over the first 3 days in the ICU (OR, 1.40; 95% CI, 1.19-1.65), respiratory failure within the first 24 hrs in the ICU (OR, 3.12; 95% CI, 1.54-6.33), and inadequate empirical antimicrobial therapy in patients with "nonsurgical sepsis" (OR, 8.14; 95% CI, 1.98-33.5), whereas adequate empirical antimicrobial therapy in "surgical sepsis" (OR, 0.37; 95% CI, 0.18-0.77) and urologic sepsis (OR, 0.14; 95% CI, 0.05-0.41) was a protective factor. Regarding early mortality (<3 days), factors associated with fatality were immunosuppression (OR, 4.57; 95% CI, 1.69-13.87), chronic cardiac failure (OR, 9.83; 95% CI, 1.98-48.69) renal failure within the first 24 hrs in the unit (OR, 8.63; 95% CI, 3.31-22.46), and respiratory failure within the first 24 hrs in the ICU (OR, 12.35; 95% CI, 4.50-33.85). Fungal infection (OR, 47.32; 95% CI, 5.56-200.97) and previous antibiotic therapy within the last month (OR, 2.23; 95% CI, 1.1-5.45) were independent variables related to administration of inadequate antibiotic therapy. In patients admitted to the ICU for sepsis, the adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome, although early mortality rate was unaffected by the appropriateness of empirical antibiotic therapy.
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                Author and article information

                Journal
                Open Forum Infect Dis
                Open Forum Infect Dis
                ofid
                Open Forum Infectious Diseases
                Oxford University Press (US )
                2328-8957
                November 2018
                24 October 2018
                24 October 2018
                : 5
                : 11
                : ofy278
                Affiliations
                [1 ]Pediatric Critical Care Medicine, Nationwide Children’s Hospital, Columbus, Ohio
                [2 ]Biostatistics Core, The Research Institute, Nationwide Children’s Hospital, Columbus, Ohio
                Author notes
                Correspondence: T. Karsies, MD, MPH, 700 Children’s Drive, Columbus, OH 43205 ( todd.karsies@ 123456nationwidechildrens.org ).
                Author information
                http://orcid.org/0000-0001-6822-6952
                Article
                ofy278
                10.1093/ofid/ofy278
                6247662
                5e919098-61a6-4d10-8f13-68cebf92a073
                © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 14 August 2018
                : 23 October 2018
                Page count
                Pages: 7
                Categories
                Major Articles

                drug resistance,risk factors,pediatric intensive care unit,gram-negative bacterial infections,critical illness

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