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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.

ABSTRACT: 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.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.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.

SUBMITTER: Ye M

PROVIDER: S-EPMC4705617 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:Infection is a severe complication of allo-HSCT in children, however, the accurate detection of the infection is hard. In this study, we traced the records of 101 pediatric recipients with allo-HSCT to investigate the pathogens of infection, and collected 54 bronchoalveolar lavage fluid, 32 blood, and 15 cerebrospinal fluid samples. In these samples, 87 was with post-transplant infection and 14 without infection. Using the metagenomic next-generation sequencing (mNGS) and traditional pathogen detection, we compared their sensitivity and specificity to detect pathogens of infection. Our results showed that mNGS was more sensitive (89.7%) than conventional pathogen detection (21.8%), with a difference of 67.9% (P < 0.001), However, mNGS was less specific (78.5%) than traditional methods (92.9%), with a difference of 14.4% (P = 0.596). The sensitivity of mNGS for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 91.7, 85.7, and 90.9%, respectively. In contrast, the sensitivity of conventional testing for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 22.9, 21.4, and 18.2%, respectively. There were significant differences in the sensitivity of mNGS and conventional testing in BALF, blood, and CSF samples, with P values of 0.000, 0.000, and 0.002 respectively. Among the patients with pulmonary infection, 11 pathogens were both identified by mNGS and conventional testing, and 33 by mNGS only. The percentage with the mNGS-positive result was 44/48 (91.7%), including viruses (n = 12), bacteria (n = 17), fungi (n = 9) and mixed infections (n = 6). Among the patients diagnosed with fungal pneumonia (n = 9), the most prevalent pathogenic fungi were Pneumocystis jiroveci (n = 6), which were also detected in 4 patients with mixed infectious pneumonia. In the 28 blood specimens of patients with bloodstream infections or viremia, five patients were positive by both mNGS and conventional testing, 19 were positive by mNGS, and 1 was positive by traditional testing only. The percentage with the mNGS-positive results was 24/28 (85.7%), including viruses (n = 12), bacteria (n = 4), fungi (n = 3), and mixed infections (n = 5). Of the 15 CSF specimens enrolled, 11 patients were eventually diagnosed with CNS infections. Ten pathogens were identified by mNGS in the 11 patients, including viruses (n = 8), bacteria (n = 1), and fungi (n = 1). These results suggest that mNGS is more sensitive than conventional pathogen detection for diagnosing infections post HSCT in children which may help the clinic diagnosis. Pneumocystis jiroveci was the most frequent pathogen of pulmonary infections post-transplant, while viruses were the most common pathogens of CNS infections in allo-HSCT recipients.

Project description:Cat-scratch disease (CSD) is an anthropozoonotic infection caused by Bartonella henselae, and it is one of the most common causes of lymph node infections in children and adolescents. B. henselae, belonging to the genus Bartonella, is a common human pathogen of human beings. CSD commonly develops as a result of cat scratches and bites or when injured skin comes into contact with cat saliva. The manifestation of CSD clinically differs for each patient based on their immune system. Individuals who have healthy immune systems generally manifest minimal clinical symptoms and do not necessitate any form of treatment. However, patients who have hypo-immunity require prompt medical attention due to the potential manifestation of severe symptoms that affect multiple systems of the body. Long latency and atypical clinical manifestations are characteristics of CSD. Bartonella isolation and identification are challenging procedures that require specialized equipment. There is no gold standard method for CSD diagnosis, and misdiagnosis and missed diagnosis rates are typically high. We present the case of a middle-aged male patient who developed fever, chills, anal distension, dizziness, and muscle pain for 10 days. The patient had a documented history of cat bites 1 month prior to the onset of symptoms. Following admission, he underwent an examination to determine superficial lymphadenopathy and hypoimmunity. Additionally, he had a fever during the disease. As the patient refused a needle biopsy of lymph nodes, metagenomic next-generation sequencing (mNGS) was employed and B. henselae was detected in the peripheral blood. The patient was diagnosed with CSD and treated with a combination of azithromycin and doxycycline. The fever symptoms were alleviated, and the patient was ultimately discharged. As a result of this case, we suggest that mNGS be used as a crucial supplementary diagnostic tool for individuals with compromised immune systems who may have CSD, especially when conventional diagnostic methods are inconclusive.

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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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