Severe Sepsis With Septic Shock as a Consequence of a Severe Hospital-Acquired Pneumonia Resulting From Legionella Pneumophila in Children: A Case Series and Literature Review

Author(s):  
Min Ding ◽  
Chunfeng Yang ◽  
Yu-mei Li

Abstract BackgroundLegionella pneumophila is responsible for hospital or community-acquired pneumonia in adults. Immunocompromised patients with Legionella pneumophila infection are associated with rapidly severe clinical course and high mortality rates. Legionella pneumophila infection is rare in children, especially combined with extrapulmonary manifestations. In this report, we describe 2 children of severe hospital-acquired pneumonia and septic shock resulting from Legionella pneumophila. Standardized metagenomics next-generation sequencing allowed early diagnosis. Appropriate antibiotic therapy and timely extracorporeal life support were effective in achieving complete recovery. This is the first report of children with septic shock related to Legionella pneumophila infections diagnosed by metagenomics next-generation sequencing and recovered successfully.Case presentationThere were 2 cases about septic shock resulting from Legionella pneumophila. One was a six-month girl with congenital biliary atresia who underwent liver transplantation. She was suspected for rejecting the liver and admitted to hospital. The other one was a five-year-old boy with Burkitt lymphoma who was in the end of early chemotherapy. They both presented with fever, cough or shortness of breath during hospitalization. And they were transferred to PICU because of worsening dyspnea and decreased blood pressure. Patients were diagnosed by severe sepsis with septic shock likely resulting from hospital-acquired pneumonia. Metagenomics next-generation sequencing indicated L. pneumophila in blood and sputum. Aggressive intravenous fluids resuscitation and vasopressors were initiated on arrival to PICU, and they were placed on mechanical ventilation and continuous renal replacement therapy. Intravenous antibiotic therapy followed by azithromycin. Finally, the patients recovered without any long-term sequelae.ConclusionsThough sepsis or sepsis shock caused by Legionella pneumophila is rare in children, it can occur at high-risk population. Metagenomics next-generation sequencing is useful for conforming hard-to-culture pathogens and severely ill patients. The report remind pediatric physicians that we should be aware that Legionella pneumophila can cause severe sepsis or sepsis shock, especially in immunocompromised children. It is significant to select appropriate samples and pathogen detection methods in the early stage of disease.

2016 ◽  
Vol 55 (1) ◽  
pp. 177-182 ◽  
Author(s):  
Alexander L. Greninger ◽  
Danielle M. Zerr ◽  
Xuan Qin ◽  
Amanda L. Adler ◽  
Reigran Sampoleo ◽  
...  

ABSTRACT Metagenomic next-generation sequencing (mNGS) is increasingly used for the unbiased detection of viruses, bacteria, fungi, and eukaryotic parasites in clinical samples. Whole-genome sequencing (WGS) of clinical bacterial isolates has been shown to inform hospital infection prevention practices, but this technology has not been utilized during potential respiratory virus outbreaks. Here, we report on the use of mNGS to inform the real-time infection prevention response to a cluster of hospital-acquired human parainfluenza 3 virus (HPIV3) infections at a children's hospital. Samples from 3 patients with hospital-acquired HPIV3 identified over a 12-day period on a general medical unit and 10 temporally associated samples from patients with community-acquired HPIV3 were analyzed. Our sample-to-sequencer time was <24 h, while our sample-to-answer turnaround time was <60 h with a hands-on time of approximately 6 h. Eight (2 cases and 6 controls) of 13 samples had sufficient sequencing coverage to yield the whole genome for HPIV3, while 10 (2 cases and 8 controls) of 13 samples gave partial genomes and all 13 samples had >1 read for HPIV3. Phylogenetic clustering revealed the presence of identical HPIV3 genomic sequence in the two of the cases with hospital-acquired infection, consistent with the concern for recent transmission within the medical unit. Adequate sequence coverage was not recovered for the third case. This work demonstrates the promise of mNGS for providing rapid information for infection prevention in addition to microbial detection.


2021 ◽  
Vol 15 (1) ◽  
pp. 98-110
Author(s):  
Alveiro Erira ◽  
Dabeiba Adriana García Robayo ◽  
Andrés Ignacio Chalá ◽  
Andrei Moreno Torres ◽  
Eliana Elisa Muñoz Lopez ◽  
...  

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world, and the bacterial microbiome has been considered a risk factor that could play an important role in carcinogenesis. Objective: A bacteriome study was performed by next-generation sequencing in dental plaque, saliva, and tumor samples of 10 OSCC patients and compared with bacteriome in dental plaque and saliva of 10 patients without OSCC. Methods: DNA was extracted from all samples and sequenced by Illumina technology MiSeq™. Bioinformatic analyzes were performed for evaluated sequence quality, alpha and beta diversity, bidirectional analysis of variance (p <0.05), and principal component analysis. After establishing bacterial profiles associated with each sample and population, intragroup and intergroup comparisons were carried out. For bacteria identification compatible with eubiosis and dysbiosis processes, a screening was performed based on the frequency of appearance in all patient samples with and without OSCC. Lastly, frequency, average, standard deviation, Chi-square, and Mann Whitney test were calculated. Results: Out of the identified 1,231 bacteria in the populations under study, 45 bacterial species were selected, of which 34 were compatible with eubiosis, and 11 were compatible with dysbiosis. Among the bacteria compatible with eubiosis were species of Lactobacillus and Streptococcus, Chromobacterium violaceum, Enterobacter asburiae, Mycobacterium chubuense, Mycoplasma penetrans, and Brachyspira intermedia. Among the species associated with dysbiosis,  Providencia stuartii, Capnocytophaga canimorsus, Legionella pneumophila, and Mycoplasma hominis were notable. Conclusion: Thirty-four bacterial species may be associated with eubiosis or healthy states and 11 bacterial species could be associated with dysbiosis or pathogenic state, OSCC.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6561 ◽  
Author(s):  
Markus H. Antwerpen ◽  
Enrico Georgi ◽  
Alexandra Nikolic ◽  
Gudrun Zoeller ◽  
Peter Wohlsein ◽  
...  

BackgroundBetween 2008 and 2011 about 40 cases of human cowpox were reported from Germany and France. Infections had been acquired via close contact to infected, young pet rats. An identical and unique sequence of the hemagglutinin gene was found in various cowpox virus (CPXV) isolates pointing to a common source of infection. In a second CPXV outbreak in cats in a small animal clinic in Germany in 2015, four out of five hospitalized cats showed identical hemagglutinin sequences and thus, a hospital-acquired transmission had been assumed. Next-Generation Sequencing was performed in order to re-investigate the outbreaks, as epidemiological data could not confirm all cases.MethodsHomogenates of lesion material from rats, cats and humans were cultivated in cell culture. The genomes of four virus isolates, nine CPXVs from our strain collections and from DNA of three paraffin-embedded lesion materials were determined by Next Generation Sequencing (NGS). For phylogenetic analyses a MAFFT-alignment was generated. A distance matrix based on concatenated SNPs was calculated and plotted as dendrogram using Unweighted Pair Group Method with Arithmetic mean (UPGMA) for visualization.ResultsAligning of about 200.000 nucleotides of 8 virus isolates associated with the pet rat outbreak revealed complete identity of six genomes, the remainder two genomes differed in as little as 3 SNPs. When comparing this dataset with four already published CPXV genomes also associated with the pet rat outbreak, again a maximum difference of 3 SNPs was found. The outbreak which lasted from 2008 till 2011 was indeed caused by a single strain which has maintained an extremely high level of clonality over 4 years. Aligning genomic sequences from four cases of feline cowpox revealed 3 identical sequences and one sequence which differed in 65 nucleotides. Although identical hemagglutinin sequences had been obtained from four hospitalized cats, genomic sequencing proved that a hospital-acquired transmission had occurred in only three cats.ConclusionAnalyzing the rather short sequence of the hemagglutinin gene is not sufficient to conduct molecular trace back analyses. Instead, whole genome sequencing is the method of choice which can even be applied to paraffin-embedded specimens.


2021 ◽  
Vol 8 ◽  
Author(s):  
Charlotte Michel ◽  
Michela Raimo ◽  
Vladimir Lazarevic ◽  
Nadia Gaïa ◽  
Nina Leduc ◽  
...  

Background:Mycoplasma hominis and Ureaplasma spp. are responsible for opportunistic infections in transplant patients, sometimes causing a life-threatening hyperammonemia syndrome. Both pathogens are not identified with standard microbiology techniques, resulting in missed or delayed diagnosis. We present a clinical case that illustrates the added value that next-generation sequencing (NGS) may offer in the diagnosis of respiratory infections in immune-compromised patients.Results: A 55 years-old man with idiopathic pulmonary fibrosis underwent double lung transplantation. He received antibiotic prophylaxis with piperacillin-tazobactam and azythromycin. At day 4 post-transplantation (PTx), the patient presented an acute respiratory distress. A broncho-alveolar lavage (BAL) was performed. At day 5 PTx, the patient presented a status epilepticus due to diffuse cerebral oedema. Serum ammonia concentration was 661 μg/dL. BAL bacterial culture was negative. Because of the clinical presentation, special cultures were performed and identified 100.000 CFU/mL of M. hominis and Ureaplasma spp. and specific PCRs were positive for M. hominis and Ureaplasma parvum. Antibiotic therapy was shifted to therapeutic dose of azithromycin and doxycycline; within 48 h ammonia serum concentrations returned to normal but the coma persisted several weeks, followed by a persistent frontal lobe syndrome. A follow-up BAL was performed on day 11 Ptx. The Mycoplasma/Ureaplasma culture was negative, yet the specific PCRs remained positive. Bacterial culture found 100 CFU/mL of Staphylococcus aureus and viral culture was positive for Herpes Simplex Virus-1. These results were confirmed by metagenomic next-generation sequencing (mNGS). In the bacterial fraction, the majority of reads belonged to Corynebacterium propinquum (34.7%), S. aureus (24.1%) and Staphylococcus epidermidis (17.1%). Reads assigned to M. hominis, Ureaplasma urealyticum and parvum represented 0.71, 0.13, and 0.04% of the bacterial fraction and corresponded to 6.9 × 103, 9.7 × 102, and 3.7 × 102 genome equivalents per mL of BAL fluid, respectively. These results are in favor of a cure of the atypical infection.Conclusions: mNGS offered added diagnostic and quantitative values compared to PCR tests, which can remain positive after resolved infections. The initiation of appropriate antibiotic therapy would have occurred earlier on, possibly resulting in a better clinical outcome if mNGS had been performed in a routine fashion.


2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Maria K. Abril ◽  
Adam S. Barnett ◽  
Kara Wegermann ◽  
Eric Fountain ◽  
Andrew Strand ◽  
...  

Abstract We report the case of a 60-year-old man with septic shock due to Capnocytophaga canimorsus that was diagnosed in 24 hours by a novel whole-genome next-generation sequencing assay. This technology shows great promise in identifying fastidious pathogens, and, if validated, it has profound implications for infectious disease diagnosis.


2018 ◽  
Author(s):  
Markus H. Antwerpen ◽  
Enrico Georgi ◽  
Alexandra Nikolic ◽  
Gudrun Zöller ◽  
Peter Wohlsein ◽  
...  

AbstractBackgroundBetween 2008 and 2011 about 40 cases of human cowpox were reported from Germany and France. Infections had been acquired via close contact to infected, young pet rats. Sequencing of the hemagglutinin gene of various cowpox virus (CPXV) isolates resulted in an identical and unique sequence in each case pointing to a common source. In a second CPXV outbreak in cats in a small animal clinic in Germany in 2015, four out of five hospitalized cats showed identical hemagglutinin sequences and thus, a hospital-acquired transmission was assumed.MethodsHomogenates of lesion material from rats, cats and humans were cultivated in cell culture. The genomes of 4 virus isolates, 9 CPXVs from our strain collections and from DNA of 3 paraffin-embedded lesion materials were determined by Next Generation Sequencing (NGS). For phylogenetic analyses a MAFFT-alignment was generated. A distance matrix based on concatenated SNPs was calculated and plotted as dendrogram using Unweighted Pair Group Method with Arithmetic mean (UPGMA) for visualization.ResultsAligning of about 200.000 nucleotides of 8 virus isolates associated with the pet rat outbreak revealed complete identity of six genomes, the remainder two genomes differed in as little as 3 SNPs. When comparing this dataset with four already published CPXV genomes also associated with the pet rat outbreak, again a maximum difference of 3 SNPs was found. The outbreak which lasted from 2008 till 2011 was indeed caused by a single strain which has maintained an extremely high level of clonality over 4 years.Aligning genomic sequences from 4 cases of feline cowpox revealed 3 identical sequences and one sequence which differed in 65 nucleotides. Although identical hemagglutinin sequences had been obtained from four hospitalized cats, genomic sequencing proved that a hospital-acquired transmission had occurred in only three cats.DiscussionAnalyzing the rather short sequence of the hemagglutinin gene is not sufficient to conduct molecular trace back analyses. Instead, whole genome sequencing is the method of choice which can even be applied to paraffin-embedded specimens.Funding StatementThis publication was supported by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 653316.This study was also supported in part by the European Union’s Horizon 2020 research and innovation program under grant agreement No 643476 (COMPARE).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


2021 ◽  
Vol 8 ◽  
Author(s):  
Limin Sun ◽  
Ziyue Yang ◽  
Fei Yang ◽  
Zhenhua Wang ◽  
Hongqiang Li ◽  
...  

A 51-year-old woman was transferred to the intensive care unit with such symptoms as fever, swollen left knee joint, pain and hypotension. After preliminary evaluation, she was diagnosed as suffering acute suppurative arthritis and septic shock. Then, she was rescued and prescribed to receive treatment with broad-spectrum antibiotics. However, there was no source of infection identified except for the knee joint. The bacterial and fungal cultures of blood samples and articular effusion were shown to be negative, while the results obtained from the next-generation sequencing of blood and articular effusion revealed that Mycobacterium tuberculosis was positive. The patient was then put on five combinations of anti-tuberculosis therapeutic treatment. Nevertheless, despite the active anti-tuberculosis treatment put in place, her general condition still deteriorated progressively. As the level of her bilirubin continued to rise, further treatment was affected, which prompted the change made to the anti-tuberculosis treatment program. Her clinical condition continued to deteriorate, which led to the development of unstable vital signs and the multiple organ dysfunction syndrome. In spite of our best efforts to save her life, the patient still ended up with death.


2016 ◽  
Author(s):  
Alexander L. Greninger ◽  
Danielle M Zerr ◽  
Xuan Qin ◽  
Amanda L. Adler ◽  
Janet A. Englund ◽  
...  

AbstractMetagenomic next-generation sequencing (mNGS) is increasingly used for the unbiased detection of viruses, bacteria, fungi, and eukaryotic parasites in clinical samples. Whole genome sequencing (WGS) of clinical bacterial isolates has been shown to inform hospital infection prevention practices, but the use of this technology during potential respiratory virus outbreaks has not been taken advantage of. Here, we report on the use of mNGS to inform the real-time infection prevention response to a cluster of hospital-acquired human parainfluenza 3 virus (HPIV3) infections at a children’s hospital. Isolates from 3 patients with hospital-acquired HPIV3 identified over a 12-day period on a general medical unit and 10 temporally-associated isolates from patients with community-acquired of HPIV3 were analyzed. Our sample-to-sequencer time was <24 hours while our sample-to-answer turn-around time was <60 hours with a hands-on time of approximately 6 hours. Eight (2 case isolates and 6 control isolates) of 13 samples had sufficient sequencing coverage to yield whole genomes for HPIV3, while 10 (2 cases and 8 controls) of 13 samples gave partial genomes and all 13 samples had >1 read to HPIV3. Phylogenetic clustering revealed the presence of identical HPIV3 genomic sequence in the two of the cases with hospital-acquired infection, consistent with the concern for recent transmission within the medical unit. Adequate sequence coverage was not recovered for the third case. This work demonstrates the promise of mNGS to provide actionable information for infection control in addition to microbial detection.


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