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      Rapid diagnosis of Propionibacterium acnes infection in patient with hyperpyrexia after hematopoietic stem cell transplantation by next-generation sequencing: a case report

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          Abstract

          Background

          The rapid determination of pathogenic agent is very important to clinician for guiding their clinical medication. However, current diagnostic methods are of limitation in many aspects, such as detecting range, time-consuming, specificity and sensitivity. In this report, we apply our new-developing pathogen detection method to clarify that Propionibacterium acnes is the causative agent of a two-year-old boy with juvenile myelomonocytic leukemia presenting clinical symptoms including serious rash and hyperpyrexia while traditional clinical methods of diagnosis fail to detect the pathogenic agent and multiple antimicrobial drugs are almost ineffective Propionibacterium acnes is confirmed to be the infectious agent by quantitative real-time polymerase chain reaction.

          Case presentation

          After haploidentical hematopoietic stem cell transplantation, a two-year-old boy with juvenile myelomonocytic leukemia presented to a pediatrist in a medical facility with hyperpyrexia and red skin rash which later changed to black skin rash all over his body. Traditional diagnostic assays were unrevealing, and several routine antimicrobial treatments were ineffective, including the vancomycin, meropenem, tobramycin, cefepime and rifampin. In this case, pediatrist resorted to the next-generation sequencing technology for uncovering potential pathogens so as to direct their use of specific drugs against pathogenic bacteria. Therefore, based on the BGISEQ100 (Ion Proton System) which performed sequencing-by-synthesis, with electrochemical detection of synthesis, and each such reaction coupled to its own sensor, which are in turn organized into a massively parallel sensor array on a complementary metal-oxidesemiconductor chip, we detect and identify the potential pathogens. As a result, we detected a significantly higher abundance of skin bacteria Propionibacterium acnes in patient’s blood than controls. It had been reported that patients infected by Propionibacterium acnes almost always had history of immunodeficiency, trauma or surgery. Considering this possible cause, antimicrobial treatment was adjusted to target this rare opportunistic pathogen. Fever and black skin rashes were rapidly reduced after administrating specific drugs against Propionibacterium acnes.

          Conclusion

          This case showed our new-developing pathogen detection method was a powerful tool in assisting clinical diagnosis and treatment. And it should be paid more attention to Propionibacterium acnes infection in clinical cases.

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          Most cited references13

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          Propionibacterium acnes: from commensal to opportunistic biofilm-associated implant pathogen.

          Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections have gained more attention due to improved diagnostic procedures, such as sonication of explanted foreign materials and prolonged cultivation time of up to 14 days for periprosthetic biopsy specimens, and improved molecular methods, such as broad-range 16S rRNA gene PCR. Implant-associated infections caused by P. acnes are most often described for shoulder prosthetic joint infections as well as cerebrovascular shunt infections, fibrosis of breast implants, and infections of cardiovascular devices. P. acnes causes disease through a number of virulence factors, such as biofilm formation. P. acnes is highly susceptible to a wide range of antibiotics, including beta-lactams, quinolones, clindamycin, and rifampin, although resistance to clindamycin is increasing. Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria. Most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam. While recently reported data showed a good efficacy of rifampin against P. acnes biofilms, prospective, randomized, controlled studies are needed to confirm evidence for combination treatment with rifampin, as has been performed for staphylococcal implant-associated infections.
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            Viral pathogen discovery

            Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease.
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              Propionibacterium acnes: infection beyond the skin.

              Propionibacterium acnes is a Gram-positive bacterium that forms part of the normal flora of the skin, oral cavity, large intestine, the conjunctiva and the external ear canal. Although primarily recognized for its role in acne, P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections. These include infections of the bones and joints, mouth, eye and brain. Device-related infections include those of joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer, SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, sarcoidosis and sciatica. If an active role in these conditions is established there are major implications for diagnosis, treatment and protection. Genome sequencing of the organism has provided an insight into the pathogenic potential and virulence of P. acnes.
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                Author and article information

                Contributors
                yemzchina@163.com
                weiwei3@genomics.cn
                568329311@qq.com
                liyingzhen@genomics.cn
                chengshaomin@genomics.cn
                wangkang1@genomics.cns
                408915649@qq.com
                840796596@qq.com
                972930260@qq.com
                nina@genomics.cn
                jianghui@genomics.cn
                weimeitiantang1213@163.com
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                8 January 2016
                8 January 2016
                2015
                : 16
                : 5
                Affiliations
                [ ]BGI-Guangdong, BGI-Shenzhen, Guangzhou, 510006 China
                [ ]BGI-Guangzhou, Guangzhou Key Laboratory of Cancer Trans-Omics Research, Guangzhou, China
                [ ]Hematopoietic Stem Cell Transplant Center, Guangzhou Women and Children Medical Center, Guangzhou, 510000 China
                [ ]BGI-Shenzhen, Shenzhen, 518083 China
                Article
                1306
                10.1186/s12879-015-1306-0
                4705617
                28e5ff4c-e18c-47df-a957-eaba6d882c1c
                © Ye et al. 2016

                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.

                History
                : 10 July 2015
                : 1 December 2015
                Funding
                Funded by: Guangzhou Key Laboratory of Cancer Trans-Omics Research
                Award ID: GZ2012, NO348
                Award Recipient :
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2016

                Infectious disease & Microbiology
                propionibacterium acnes,hyperpyrexia,hematopoietic stem cell transplantation,next generation sequencing,diagnosis

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