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      High Prevalence of Faecal Carriage of ESBL-Producing Enterobacteriaceae among Children in Dar es Salaam, Tanzania

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          Abstract

          Background

          Faecal carriage of ESBL-producing bacteria is a potential risk for transmission and infection. Little is known about faecal carriage of antibiotic resistance in Tanzania. This study aimed to investigate the prevalence of faecal carriage of ESBL-producing Enterobacteriaceae and to identify risk factors for carriage among young children in Tanzania.

          Methodology/Principal Findings

          From August 2010 to July 2011, children below 2 years of age were recruited in Dar es Salaam, including healthy community children (n = 250) and children hospitalized due to diarrhoea (n = 250) or other diseases (n = 103). ChromID ESBL agar and ChromID CARBA SMART agar were used for screening. Antimicrobial susceptibility testing was performed by the disk diffusion method. ESBL genotypes were identified by Real-Time PCR and sequencing.

          The overall prevalence of ESBL carriage was 34.3% (207/ 603). The prevalence of ESBL carriage was significantly higher among hospitalized children (50.4%), compared to community children (11.6%; P < 0.001; OR = 7.75; 95% CI: 4.99–12.03). We found high prevalence of Multidrug-resistance (94%) among Escherichia coli and Klebsiella pneumoniae isolates. No resistance to carbapenems was detected. For the majority of isolates (94.7%) we detected a bla CTX-M-15-like gene. In addition, the plasmid mediated AmpC beta-lactamase CMY-2 was detected for the first time in Tanzania. ESBL prevalence was significantly higher among HIV positive (89.7%) than HIV negative (16.9%) children (P = 0.001; OR = 9.99; 95% CI: 2.52–39.57). Use of antibiotics during the past 14 days and age below 1 year was also associated with ESBL carriage.

          Conclusions/Significance

          We report a high rate of faecal carriage of ESBL-producing Enterobacteriaceae among children below 2 years of age in Tanzania, particularly those with HIV-infection. Resistance to a majority of the available antimicrobials commonly used for children in Tanzania leaves few treatment options for infections when caused by these bacteria.

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          Most cited references22

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          Fecal Colonization With Extended-spectrum Beta-lactamase-Producing Enterobacteriaceae and Risk Factors Among Healthy Individuals: A Systematic Review and Metaanalysis.

          Gut colonization is a risk factor for infections with extended-spectrum beta-lactamase (ESBL)-producing organisms. We aimed to determine the ESBL class A reservoir among healthy individuals.
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            Risk of infection following colonization with carbapenem-resistant Enterobactericeae: A systematic review.

            Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as important health care-associated pathogens. Colonization precedes infection but the risk of developing infection amongst those colonized with CRE is not clear.
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              Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study

              Background Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established. Methods We assessed the incidence of bloodstream infection and risk factors for fatal outcome in a prospective cohort study of 1828 consecutive admissions of children aged zero to seven years with signs of systemic infection. Blood was obtained for culture, malaria microscopy, HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical features, underlying diseases, antimicrobial drug use and patients' outcome. Results The incidence of laboratory-confirmed bloodstream infection was 13.9% (255/1828) of admissions, despite two thirds of the study population having received antimicrobial therapy prior to blood culture. The most frequent isolates were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9%) of the children with laboratory-confirmed bloodstream infection died. The mortality rate from Gram-negative bloodstream infection (43.5%) was more than double that of malaria (20.2%) and Gram-positive bloodstream infection (16.7%). Significant risk factors for death by logistic regression modeling were inappropriate treatment due to antimicrobial resistance, HIV infection, other underlying infectious diseases, malnutrition and bloodstream infection caused by Enterobacteriaceae, other Gram-negatives and candida. Conclusion Bloodstream infection was less common than malaria, but caused more deaths. The frequent use of antimicrobials prior to blood culture may have hampered the detection of organisms susceptible to commonly used antimicrobials, including pneumococci, and thus the study probably underestimates the incidence of bloodstream infection. The finding that antimicrobial resistance, HIV-infection and malnutrition predict fatal outcome calls for renewed efforts to curb the further emergence of resistance, improve HIV care and nutrition for children.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 December 2016
                2016
                : 11
                : 12
                : e0168024
                Affiliations
                [1 ]National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway
                [2 ]Department of Clinical Science, University of Bergen, Bergen, Norway
                [3 ]Department of Microbiology, Haukeland University Hospital, Bergen, Norway
                [4 ]Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
                Ross University School of Veterinary Medicine, SAINT KITTS AND NEVIS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MGT BB NL SJM.

                • Data curation: MGT SJM.

                • Formal analysis: MGT ØK SJM.

                • Funding acquisition: NL.

                • Investigation: MGT ØK SJM.

                • Methodology: MGT BB ØK NL SJM.

                • Project administration: NL SJM.

                • Resources: MGT BB ØK SYM NL SJM.

                • Software: MGT BB ØK SJM.

                • Supervision: NL SJM.

                • Validation: MGT BB ØK SYM NL SJM.

                • Visualization: MGT BB ØK SYM NL SJM.

                • Writing – original draft: MGT.

                • Writing – review & editing: MGT BB ØK SYM NL SJM.

                Article
                PONE-D-16-38653
                10.1371/journal.pone.0168024
                5148075
                27936054
                46b7c509-29c0-4de2-ac02-ba5c95dca6e1
                © 2016 Tellevik et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 September 2016
                : 25 November 2016
                Page count
                Figures: 1, Tables: 4, Pages: 13
                Funding
                Funded by: This study was supported by the University of Bergen, Norway, and by the National Centre for Tropical Infectious Diseases, Haukeland University Hospital, Norway. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Award Recipient :
                Funded by: "The author(s) received no specific funding for this work."
                Award Recipient :
                This study was supported by the University of Bergen, Norway, and by the National Centre for Tropical Infectious Diseases, Haukeland University Hospital, Norway. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
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