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      A retrospective study of factors which determine a negative blood culture in Cambodian children diagnosed with enteric fever

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          Abstract

          Background: Blood cultures are used to confirm a diagnosis of enteric fever but reported sensitivities can be as low as 40%.

          Aims: To determine the factors associated with a negative blood culture in Cambodian children with suspected enteric fever.

          Methods: In a retrospective study of hospitalised Cambodian children given a discharge diagnosis of enteric fever, the following factors associated with a negative blood culture were analysed: age, blood culture volume, prior antibiotic therapy, duration of illness and disease severity.

          Results: In 227 hospitalised Cambodian children with a discharge diagnosis of enteric fever, it was confirmed in 70% by a positive blood culture. There was no association between a negative blood culture and younger age, lower blood volumes for culture, prior antibiotic therapy, a late presentation or milder disease.

          Conclusions: Although blood culture sensitivity was higher than expected, alternative simple, rapid and sensitive tests are needed for diagnosing enteric fever.

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          Most cited references8

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          A Prospective Study of the Causes of Febrile Illness Requiring Hospitalization in Children in Cambodia

          Background Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children hospitalised in Siem Reap province, Cambodia. Methods and Findings A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12th 2009 and October 12th 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8–6.4) years, with 850 (69%) episodes in children <5 years. Common microbiological diagnoses were dengue virus (16.2%), scrub typhus (7.8%), and Japanese encephalitis virus (5.8%). 76 (6.3%) episodes had culture-proven bloodstream infection, including Salmonella enterica serovar Typhi (22 isolates, 1.8%), Streptococcus pneumoniae (13, 1.1%), Escherichia coli (8, 0.7%), Haemophilus influenzae (7, 0.6%), Staphylococcus aureus (6, 0.5%) and Burkholderia pseudomallei (6, 0.5%). There were 69 deaths (5.6%), including those due to clinically diagnosed pneumonia (19), dengue virus (5), and melioidosis (4). 10 of 69 (14.5%) deaths were associated with culture-proven bloodstream infection in logistic regression analyses (odds ratio for mortality 3.4, 95% CI 1.6–6.9). Antimicrobial resistance was prevalent, particularly in S. enterica Typhi, (where 90% of isolates were resistant to ciprofloxacin, and 86% were multi-drug resistant). Comorbid undernutrition was present in 44% of episodes and a major risk factor for acute mortality (OR 2.1, 95% CI 1.1–4.2), as were HIV infection and cardiac disease. Conclusion We identified a microbiological cause of fever in almost 50% of episodes in this large study of community-acquired febrile illness in hospitalized children in Cambodia. The range of pathogens, antimicrobial susceptibility, and co-morbidities associated with mortality described will be of use in the development of rational guidelines for infectious disease treatment and control in Cambodia and South-East Asia.
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            Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever.

            The recovery of Salmonella typhi from blood, rectal swab, urine, bone-marrow, and rose spots was compared in 62 patients with typhoid fever, most of whom had received some antibiotic therapy before presentation. S. typhi was isolated from culture of bone-marrow in 56 patients (90%); in contrast, S. typhi was recovered from blood in only 25 (40%), from stool in 23 (37%), and urine in 4 (7%). S. typhi was isolated from 24 (63%) of 38 patients who had rose-spot cultures. If culture sites had been limited to blood, stool, and urine, the bacteriological diagnosis would have been missed in 24 patients.
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              Enteric fever in Cambodian children is dominated by multidrug-resistant H58 Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin.

              Infections with Salmonella enterica serovar Typhi isolates that are multidrug resistant (MDR: resistant to chloramphenicol, ampicillin, trimethoprim-sulphamethoxazole) with intermediate ciprofloxacin susceptibility are widespread in Asia but there is little information from Cambodia. We studied invasive salmonellosis in children at a paediatric hospital in Siem Reap, Cambodia. Between 2007 and 2011 Salmonella was isolated from a blood culture in 162 children. There were 151 children with enteric fever, including 148 serovar Typhi and three serovar Paratyphi A infections, and 11 children with a non-typhoidal Salmonella infection. Of the 148 serovar Typhi isolates 126 (85%) were MDR and 133 (90%) had intermediate ciprofloxacin susceptibility. Inpatient antimicrobial treatment was ceftriaxone alone or initial ceftriaxone followed by a step-down to oral ciprofloxacin or azithromycin. Complications developed in 37/128 (29%) children admitted with enteric fever and two (1.6%) died. There was one confirmed relapse. In a sample of 102 serovar Typhi strains genotyped by investigation of a subset of single nucleotide polymorphisms, 98 (96%) were the H58 haplotype, the majority of which had the common serine to phenylalanine substitution at codon 83 in the DNA gyrase. We conclude that antimicrobial-resistant enteric fever is common in Cambodian children and therapeutic options are limited. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Paediatr Int Child Health
                Paediatr Int Child Health
                YPCH
                ypch20
                Paediatrics and International Child Health
                Taylor & Francis
                2046-9047
                2046-9055
                2 April 2016
                27 April 2016
                : 36
                : 2
                : 118-121
                Affiliations
                [ a ]Angkor Hospital for Children , Siem Reap, Cambodia
                [ b ]Department of Infectious Diseases, Addenbrookes Hospital , Cambridge, UK
                [ c ]Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand
                [ d ]Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford , UK
                [ e ]Clinical Sciences, Liverpool School of Tropical Medicine , UK
                Author notes
                [* ]Correspondence to: R Bousfield, Department of Infectious Diseases, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK. Email: rachel.bousfield@ 123456addenbrookes.nhs.uk
                Article
                1109242
                10.1179/2046905515Y.0000000009
                5353737
                25845519
                7558efc5-e107-4aa5-83fa-d8a5a3313e86
                © 2016 The Authors. Published by Informa UK Limited, trading as Taylor & Francis Group

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

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                Figures: 0, Tables: 2, Equations: 0, References: 12, Pages: 4
                Categories
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                Short Communication

                Pediatrics
                enteric fever,typhoid,cambodia,children,blood culture,salmonella,paediatric,angkor hospital for children

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