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      Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh

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          Abstract

          Background

          Non-typhoidal Salmonella (NTS) and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia.

          Methodology

          We performed a retrospective age-matched case-control study of patients admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between February 2009 and March 2013. We compared demographic, clinical, microbiological, and outcome variables of NTS bacteremic patients with age-matched S. Typhi bacteremic patients, and a separate comparison of patients with NTS bacteremia and patients with NTS gastroenteritis.

          Principal Findings

          Of 20 patients with NTS bacteremia, 5 died (25% case fatality), compared to none of 60 age-matched cases of S. Typhi bacteremia. In univariate analysis, we found that compared with S. Typhi bacteremia, cases of NTS bacteremia had more severe acute malnutrition (SAM) in children under five years of age, less often presented with a duration of fever ≥ 5 days, and were more likely to have co-morbidities on admission such as pneumonia and clinical signs of sepsis (p<0.05 in all cases). In multivariable logistic regression, SAM, clinical sepsis, and pneumonia were independent risk factors for NTS bacteremia compared with S. Typhi bacteremia (p<0.05 in all cases). Notably, we found marked differences in antibiotic susceptibilities, including NTS strains resistant to antibiotics commonly used for empiric therapy of patients suspected to have typhoid fever.

          Conclusions/Significance

          Diarrheal patients with NTS bacteremia more often presented with co-morbidities and had a higher case fatality rate compared to those with typhoidal bacteremia. Clinicians in regions where both typhoid and NTS bacteremia are prevalent need to be vigilant about the possibility of both entities, especially given notable differences in antibiotic susceptibility patterns.

          Author Summary

          Salmonella are a group of bacteria that cause illnesses and death worldwide. There are two types of Salmonella–Typhi and non-typhoidal (NTS). In humans, the majority of illnesses caused by NTS are related to gastro-intestinal problems, though uncommonly, it also invades the bloodstream. On the other hand, typhoid fever caused by Salmonella typhi commonly invades the bloodstream. Since the treatment of the two types may differ, we wanted to compare the risk factors for each. We studied patients who had NTS or Typhi isolated from blood in a diarrheal hospital in Bangladesh. We observed that patients with NTS bloodstream infection frequently presented with severe malnutrition, clinically diagnosed sepsis and pneumonia compared to those with typhoid fever. We also found that NTS and Typhi differed in what antibiotics they were sensitive to. These observations may help our clinicians to initiate aggressive treatment from the very beginning of the illness in children with NTS bacteremia in order to attain better outcomes.

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          Most cited references24

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          The global burden of nontyphoidal Salmonella gastroenteritis.

          To estimate the global burden of nontyphoidal Salmonella gastroenteritis, we synthesized existing data from laboratory-based surveillance and special studies, with a hierarchical preference to (1) prospective population-based studies, (2) "multiplier studies," (3) disease notifications, (4) returning traveler data, and (5) extrapolation. We applied incidence estimates to population projections for the 21 Global Burden of Disease regions to calculate regional numbers of cases, which were summed to provide a global number of cases. Uncertainty calculations were performed using Monte Carlo simulation. We estimated that 93.8 million cases (5th to 95th percentile, 61.8-131.6 million) of gastroenteritis due to Salmonella species occur globally each year, with 155,000 deaths (5th to 95th percentile, 39,000-303,000 deaths). Of these, we estimated 80.3 million cases were foodborne. Salmonella infection represents a considerable burden in both developing and developed countries. Efforts to reduce transmission of salmonellae by food and other routes must be implemented on a global scale.
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            Antimicrobial susceptibility testing: a review of general principles and contemporary practices.

            An important task of the clinical microbiology laboratory is the performance of antimicrobial susceptibility testing of significant bacterial isolates. The goals of testing are to detect possible drug resistance in common pathogens and to assure susceptibility to drugs of choice for particular infections. The most widely used testing methods include broth microdilution or rapid automated instrument methods that use commercially marketed materials and devices. Manual methods that provide flexibility and possible cost savings include the disk diffusion and gradient diffusion methods. Each method has strengths and weaknesses, including organisms that may be accurately tested by the method. Some methods provide quantitative results (eg, minimum inhibitory concentration), and all provide qualitative assessments using the categories susceptible, intermediate, or resistant. In general, current testing methods provide accurate detection of common antimicrobial resistance mechanisms. However, newer or emerging mechanisms of resistance require constant vigilance regarding the ability of each test method to accurately detect resistance.
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              Salmonella enterica serovar Paratyphi A and S. enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal.

              Enteric fever is a major global problem. Emergence of antibacterial resistance threatens to render current treatments ineffective. There is little research or public health effort directed toward Salmonella enterica serovar Paratyphi A, because it is assumed to cause less severe enteric fever than does S. enterica serovar Typhi. There are few data on which to base this assumption, little is known of the serovar's antibacterial susceptibilities, and there is no readily available tolerable vaccination. A prospective study was conducted of 609 consecutive cases of enteric fever (confirmed by blood culture) to compare the clinical phenotypes and antibacterial susceptibilities in S. Typhi and S. Paratyphi A infections. Variables independently associated with either infection were identified to develop a diagnostic rule to distinguish the infections. All isolates were tested for susceptibility to antibacterials. Six hundred nine patients (409 with S. Typhi infection and 200 with S. Paratyphi A infection) presented during the study period. The infections were clinically indistinguishable and had equal severity. Nalidixic acid resistance, which predicts a poor response to fluoroquinolone treatment, was extremely common (75.25% of S. Paratyphi A isolates and 50.5% of S. Typhi isolates; P < .001). S. Paratyphi A was more likely to be resistant to ofloxacin (3.6% vs. 0.5%; P = .007) or to have intermediate susceptibility to ofloxacin (28.7% vs. 1.8%; P < .001) or ciprofloxacin (39.4% vs. 8.2%; P < .001). MICs for S. Paratyphi A were higher than for S. Typhi (MIC of ciprofloxacin, 0.75 vs. 0.38 microg/mL [P < .001]; MIC of ofloxacin, 2.0 vs. 0.75 microg/mL [P < .001]). The importance of S. Paratyphi A has been underestimated. Infection is common, the agent causes disease as severe as that caused by S. Typhi and is highly likely to be drug resistant. Drug resistance and lack of effective vaccination suggest that S. Paratyphi A infection may become a major world health problem.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                11 September 2015
                September 2015
                : 9
                : 9
                : e0004066
                Affiliations
                [1 ]Centre for Nutrition and Food Security (CNFS), International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh
                [2 ]Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh
                [3 ]Division of Infectious Disease, Massachusetts General Hospital, Boston, Massachusetts, United States of America
                [4 ]Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
                [5 ]Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh
                University of California San Diego School of Medicine, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KMS DTL MJC ETR. Performed the experiments: KMS DTL. Analyzed the data: KMS DTL MJC ETR. Contributed reagents/materials/analysis tools: KMS DTL. Wrote the paper: KMS DTL TA PKB DA FQ ETR MJC. Obtained permission from the IRB of the centre: KMS DTL MJC.

                [¤]

                Current address: Division of Infectious Diseases, University of Utah, Salt Lake City, Utah, United States of America

                ‡ These authors share first authorship on this work.

                Article
                PNTD-D-15-00605
                10.1371/journal.pntd.0004066
                4567379
                26361076
                83d46490-c71e-4735-a211-ef0dfdf2d4df
                Copyright @ 2015

                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
                : 12 April 2015
                : 18 August 2015
                Page count
                Figures: 0, Tables: 6, Pages: 12
                Funding
                This research was supported by core grants to the icddr,b and additionally supported by the following grants: AI100923 (to DTL), AI100023 (to ETR), and a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society of Tropical Medicine and Hygiene/ Burroughs Wellcome Fund (to DTL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The data of this manuscript have been obtained from a large prospective study with a huge data set that deals with a number of objectives. The submitted manuscript deals with one of the objectives of that data set! This data set contains some personal information of the study patients (such as name, admission date, month, area of residence) those were required during ensuring follow-up of the patients. However, during taking the consent from the parents, it has been ensured to the parents that the personal information of their children will not be disclosed, but, the study results will be published. Thus, the availability of this whole data set in the manuscript, the supplemental files, or a public repository will open all the personal information of the patients those should not be disclosed; additionally this will disclose other important information those are yet to be published. Thus, the policy of our centre (icddr,b) is that we should not make the availability of whole data set in the manuscript, the supplemental files, or a public repository. Institutional Review Board (IRB) of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) has restrictions to disclose any personal information of the patients, and on the basis of this recommendation by the IRB, the Research & Clinical Administration and Strategy (RCAS) of icddr,b has imposed these restrictions. However, it is confirmed that the part of data set related to this manuscript is available upon request and readers may contact to the RCAS of icddr,b to request the data ( http://www.icddrb.org/).

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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