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      Genome Sequencing Verifies Relapsed Infection of Helicobacter cinaedi

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          Abstract

          Background

          Recurrent infections of Helicobacter cinaedi are often reported, and long-term antimicrobial treatment is empirically recommended to prevent such infections. However, there have been no studies examining whether recurrent infections are relapses of former infections or reinfections with different clones.

          Methods

          A 69-year-old woman presented with recurrent H cinaedi bacteremia-associated cellulitis after a 51-day interval. We isolated 10 colonies from the blood cultures obtained during each of the 2 episodes and subjected them to whole-genome sequencing (WGS). High-confidence single-nucleotide polymorphisms (SNPs) were identified by an assembly based method. Heterogeneous SNP sites were identified by read mapping. The susceptibility of a representative isolate to 14 antimicrobials was also examined.

          Results

          Whole-genome sequence analysis revealed only 6 SNP sites among the 20 isolates at the whole-genome level. Based on the 6 SNPs, 5 within-host variants (referred to as genotypes) were identified. All 5 genotypes were detected in the first infection; however, only 2 genotypes were detected in the second infection. Although the H cinaedi clone showed a higher minimum inhibitory concentration to fluoroquinolones and macrolides and responsible mutations were identified, none of the 6 SNPs appeared related to additional resistance.

          Conclusions

          The second infection analyzed here was a relapse of the first infection. A certain level of within-host genomic heterogeneity of the H cinaedi clone was already present in the first infection. Our results suggest the importance of longer treatment courses to eradicate H cinaedi for preventing the relapse of its infection.

          Abstract

          Whole-genome sequencing analysis identified a relapsed infection of H cinaedi. Longer treatment courses may be required to prevent its relapsed infections. The presence of within-host heterogeneity should be considered when H cinaedi isolates are analyzed.

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          Most cited references16

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          Clinical and bacteriological characteristics of Helicobacter cinaedi infection.

          Helicobacter cinaedi was first isolated from rectal cultures from homosexual men in 1984. In the 1980s to mid 1990s, the microorganism was mainly isolated from samples from homosexual men or immunocompromised patients; however, during the last two decades, H. cinaedi has been isolated from immunocompromised and from immunocompetent individuals worldwide. In Japan, the isolation of this microorganism was first reported in 2003. Since then, many cases have been reported in hospitals across the country. Despite many reports, the etiological properties and pathogenicity of H. cinaedi remain elusive; however, we are increasingly able to recognize some of the features and the clinical relevance of infection. In particular, a long incubation period is essential for detection in an automatic blood culture system and many of the recent isolates are resistant to both macrolides and quinolones. Furthermore, there is an association between infection and severe or chronic illnesses, such as meningitis or arteriosclerosis, in addition to mild diseases such as fever, abdominal pain, gastroenteritis, proctitis, diarrhea, erysipelas, cellulitis, arthritis, and bacteremia. In this review, we introduce the current knowledge and our latest findings relating to H. cinaedi. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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            Campylobacter enteritis: a "new" disease.

            M Skirrow (1977)
            By selective culture campylobacters (C jejuni and C coli) were isolated from the faeces of 57 (7-1%) out of 803 unselected patients with diarrhoea; none were isolated from 194 people who had not got diarrhoea. Specific agglutinins were found in the sera of 31 out of 38 patients with campylobacter enteritis and 10 of them had a rising titre. Half the patients were aged 15 to 44 years, but the incidence was highest in young children. All the patients with campylobacters had a distinctive clinical illness with severe abdominal pain. Campylobacters are a relatively unrecognised cause of acute enteritis, but these findings suggest that they may be a common cause. Spread of infection was observed within 12 out of 29 households, and in these cases children were usually implicated. Several patients were apparently infected from chickens, both live and dressed, and poultry may be the primary source of the organism. In two cases dogs with diarrhoea were found to be infected with strains indistinguishable from their human contacts. Ten patients acquired their infections while travelling abroad.
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              Clinical characteristics of bacteremia caused by Helicobacter cinaedi and time required for blood cultures to become positive.

              The aim of this study was to clarify the clinical characteristics of patients with Helicobacter cinaedi bacteremia and the time required for blood cultures to become positive. The medical records of all patients with H. cinaedi bacteremia at Toranomon Hospital and Toranomon Hospital Kajigaya between March 2009 and March 2013 were retrospectively reviewed. Sixty-three patients, 34 men and 29 women with a median age of 67 years (range, 37 to 88 years), were diagnosed with H. cinaedi bacteremia. A total of 51,272 sets of blood cultures were obtained during the study period, of which 5,769 sets of blood cultures were positive for some organism and 126 sets were H. cinaedi positive. The time required for blood cultures to become positive for H. cinaedi was ≤5 days in 69 sets (55%) and >5 days in 57 sets (45%). Most patients had an underlying disease, including chronic kidney disease (21 cases), solid tumor (19 cases), hematological malignancy (13 cases), diabetes mellitus (8 cases), chronic liver disease (6 cases), and postorthopedic surgery (3 cases). Only 1 patient had no apparent underlying disease. The clinical symptoms included cellulitis in 24 cases, colitis in 7 cases, and fever only in 27 cases, including 7 cases of febrile neutropenia. The 30-day mortality rate of H. cinaedi bacteremia was 6.3%. In conclusion, most cases of H. cinaedi bacteremia occurred in immunocompromised patients. We might have overlooked nearly half of the H. cinaedi bacteremia cases if the duration of monitored blood culture samples had been within 5 days. Therefore, when clinicians suspect H. cinaedi bacteremia, the observation period for blood cultures should be extended.
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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
                May 2019
                25 April 2019
                25 April 2019
                : 6
                : 5
                : ofz200
                Affiliations
                [1 ]Center of Nephrology and Connective Tissue Disease, Japan Community Health Care Organization Hokkaido Hospital, Japan
                [2 ]Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Japan
                [3 ]Center for Animal Disease Control, University of Miyazaki, Japan
                [4 ]Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Japan
                Author notes
                Correspondence: T. Hayashi, MD, PhD, Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan ( thayash@ 123456bact.med.kyushu-u.ac.jp ).

                O. S. and Y. G. contributed equally to this study.

                Article
                ofz200
                10.1093/ofid/ofz200
                6527084
                3c235348-f4d5-4fa4-b038-c5e39950f58e
                © The Author(s) 2019. 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
                : 18 February 2019
                : 22 April 2019
                Page count
                Pages: 5
                Funding
                Funded by: Japan Society for the Promotion of Science KAKENHI
                Award ID: JP17K17933
                Categories
                Major Articles

                helicobacter cinaedi,recurrent infection,relapse,whole-genome sequencing,within-host diversity

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