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      Suspicion of respiratory tract infection with multidrug-resistant Enterobacteriaceae: epidemiology and risk factors from a Paediatric Intensive Care Unit


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          Multidrug-resistant (MDR) infections are a serious concern for children admitted to the Paediatric Intensive Care Unit (PICU). Tracheal colonization with MDR Enterobacteriaceae predisposes to respiratory infection, but underlying risk factors are poorly understood. This study aims to determine the incidence of children with suspected infection during mechanical ventilation and analyses risk factors for the finding of MDR Enterobacteriaceae in tracheal aspirates.


          A retrospective single-centre analysis of Enterobacteriaceae isolates from the lower respiratory tract of ventilated PICU patients from 2005 to 2014 was performed. Resistance status was determined and clinical records were reviewed for potential risk factors. A classification and regression tree (CRT) to predict risk factors for infection with MDR Enterobacteriaceae was employed. The model was validated by simple and multivariable logistic regression.


          One hundred sixty-seven Enterobacteriaceae isolates in 123 children were identified. The most frequent isolates were Enterobacter spp., Klebsiella spp. and E.coli. Among these, 116 (69%) isolates were susceptible and 51 (31%) were MDR. In the CRT analysis, antibiotic exposure for ≥ 7 days and presence of gastrointestinal comorbidity were the most relevant predictors for an MDR isolate. Antibiotic exposure for ≥ 7 days was confirmed as a significant risk factor for infection with MDR Enterobacteriaceae by a multivariable logistic regression model.


          This study shows that critically-ill children with tracheal Enterobacteriaceae infection are at risk of carrying MDR isolates. Prior use of antibiotics for ≥ 7 days significantly increased the risk of finding MDR organisms in ventilated PICU patients with suspected infection. Our results imply that early identification of patients at risk, rapid microbiological diagnostics and tailored antibiotic therapy are essential to improve management of critically ill children infected with Enterobacteriaceae.

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          The online version of this article (doi:10.1186/s12879-017-2251-x) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs.

          There is an association between the development of antimicrobial resistance in Staphylococcus aureus, enterococci, and gram-negative bacilli and increases in mortality, morbidity, length of hospitalization, and cost of health care. For many patients, inadequate or delayed therapy and severe underlying disease are primarily responsible for the adverse outcomes of infections caused by antimicrobial-resistant organisms. Patients with infections due to antimicrobial-resistant organisms have higher costs (approximately 6,000-30,000 dollars) than do patients with infections due to antimicrobial-susceptible organisms; the difference in cost is even greater when patients infected with antimicrobial-resistant organisms are compared with patients without infection. Strategies to prevent nosocomial emergence and spread of antimicrobial-resistant organisms are essential.
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            Combination therapy for treatment of infections with gram-negative bacteria.

            Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.
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              The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter.

              Over the past 60 years, the use of successive generations of beta-lactam antibiotics has selected successive generations of beta-lactamase enzymes, each more potent than the last. Currently, rising problems include CTX-M extended-spectrum beta-lactamases (ESBLs), plasmid-mediated AmpC beta-lactamases and KPC carbapenemases in Enterobacteriaceae, while OXA- and metallo- carbapenemases are of growing importance in Acinetobacter spp. and (less so) in other non-fermenters. Escherichia coli isolates with CTX-M ESBLs are spreading multiresistance in the community and in hospitals, while carbapenemase-producing Acinetobacter spp., mostly from intensive care, are among the most multiresistant nosocomial bacteria known and are often susceptible only to polymyxins and, potentially, tigecycline. This review discusses the epidemiology and microbiology of these resistance problems, along with possible solutions.

                Author and article information

                +49 7071 2985801 , Hanna.Renk@med.uni-tuebingen.de
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                21 February 2017
                21 February 2017
                : 17
                : 163
                [1 ]ISNI 0000 0001 0196 8249, GRID grid.411544.1, Dept. of Paediatric Cardiology, Pulmology and Intensive Care Medicine, , University Children’s Hospital Tübingen, ; Hoppe-Seyler Str. 1, Tübingen, 72076 Germany
                [2 ]ISNI 0000 0001 2190 1447, GRID grid.10392.39, Institute of Medical Microbiology and Hygiene, , University of Tübingen, ; Elfriede-Aulhorn-Str.6, Tübingen, 72076 Germany
                [3 ]ISNI 0000 0001 0196 8249, GRID grid.411544.1, Dept. of Paediatrics, Pediatric Infectious Diseases, Immunology & Pneumology/Cystic fibrosis, , University Children’s Hospital Tübingen, ; Hoppe-Seyler Str. 1, Tübingen, 72076 Germany
                Author information
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                : 12 May 2016
                : 7 February 2017
                Research Article
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                © The Author(s) 2017

                Infectious disease & Microbiology
                Infectious disease & Microbiology


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