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

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 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case report 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in Children: A Case Series and Literature Review Min Ding, Chunfeng Yang, Yu-mei Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-122218/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Legionella 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 presentation There 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. Conclusions Though 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. Pediatrics Legionella pneumophila sepsis shock metagenomics next-generation sequencing Figures Figure 1 Figure 1 Figure 2 Figure 2 Background Sepsis is the leading causes of childhood mortality worldwide and identified a highest mortality of 22.8% in developing countries [ 1 ] . Although studies demonstrate the impact of staphylococcal and streptococcal infections as leading pathogens for sepsis, only approximatively 50% children admitted to pediatric intensive care unit (PICU) with a clinical diagnosis of sepsis have a microbiologically confirmed infection [ 2 ] . Because the majority of pediatric sepsis befall very early, it is very important to identify the pathogen as soon as possible [ 3 ] . Legionella pneumophila (L. pneumophila) is an important pathogen of severe pneumonia in immunocompromised patients. It also can occur extrapulmonary manifestations. L. pneumophila in patients is difficult to identified because of nonspecific clinical symptoms. Although a variety of methods have been developed to detect L. pneumophila, it is still difficult to isolate it from blood as the gold standard [ 4 ] . As far as we know, reports about L. pneumophila with sepsis or septic shock in children are extremely rare. We describe 2 children who had severe sepsis with septic shock as a consequence of a severe hospital-acquired pneumonia (HAP) resulting from L. pneumophila. We verified L. pneumophila infection through metagenomics next-generation sequencing (mNGS) of blood and sputum. This is the first presentation of children with septic shock related to L. pneumophila infection diagnosed by mNGS in the English-language. It is important to remind pediatricians that it does occur in children, particularly in immunocompromised patients. And it is useful that we can verified pathogeny by mNGS for critically ill patients in the early course of illness. Case Presentation Case1 A six-month girl with congenital biliary atresia underwent liver transplantation. Engraftment on day 28 posttransplant was complicated by an increased alanine aminotransferase (ALT) level. She had no fever, cough and other symptoms while at home. She was suspected for rejecting the liver and admitted to hospital. On admission, her immunosuppression included tacrolimus (1.2 mg every 12 h)and methylprednisolone (12 mg every day).Her abnormal laboratory results included an ALT level of 283 U/L (normal: 7–40 U/L) and an aspartate aminotransferase (AST) level of 112.7 U/L (normal: 13–35 U/L). Empiric intravenous therapy with high-dose methylprednisolone( 80 mg intravenously every day) was initiated, along with oral tacrolimus continuously (1.2 mg every 12 h).Her ALT and AST were decreased gradually during hospitalization. On the 25th hospital day, she presented with fever, cough with whitish sputum, and shortness of breath. Coarse crackles were heard over both lung fields. Laboratory data revealed a white blood cell(WBC) count of 25.45 × 10 9 /L with neutrophil predominance (79%)(normal: 4–10 × 10 9 /L), C-reactive protein(CRP) 51.26 mg/dl (normal: 0-3.5 U/L)and procalcitonin(PCT) 0.22 ng/mL(normal: 0-0.1 U/L). Computed tomography scan of the chest showed patchy infiltrations were seen in the upper lobe of right lung and lower lobe of left lung (Fig. 1 , A). After the culture of blood and sputum, empiric antibiotics with meropenem (80 mg every 8 h), micafunginand (30 mg every day) and vancomycin (160 mg every 12 h) were administered for 6 days. Pathogenic serological and antibody-based assays, blood culture and respiratory culture were negative. On the 31th admission, the patient needed mechanic ventilation because of worsening dyspnea. She was transferred to PICU. Her vital signs on arrival to PICU were as follows: blood pressure of 80/33 mmHg (mean arterial pressure of 48.7 mmHg), a respiratory rate of 50 breaths/minute, a heart rate of 240 beats/minute, a temperature of 38.3℃, and an oxygen saturation by pulse oximetry of 85% while breathing ambient air. Physical examination revealed with rales on auscultation, low skin temperature of limbs and capillary refill time 3 seconds. After a critical care medicine evaluation was requested, the patient was diagnosed by severe sepsis with septic shock likely resulting from HAP. Aggressive intravenous fluids resuscitation and vasopressors (norepinephrine, vasopressin) were initiated on arrival to PICU, and the patient was subsequently intubated and placed on mechanical ventilation because of worsening tachypnea and increased FiO 2 requirements. Meanwhile, she was treated with continuous renal replacement therapy (CRRT) to eliminate inflammatory factors for 2 days. Empiric antibiotics with meropenem (370 mg every 8 h), caspofungin (30 mg every day) and vancomycin (140 mg every 8 h) were continued to be administered, along with oral tacrolimus and methylprednisolone. We sent samples of blood and sputum to BGI Group (Beijing, China) for mNGS. Though Serum antibody, blood culture and respiratory culture were negative, mNGS indicated L. pneumophila in blood and sputum. For blood, there was 1044 raw reads and 516 raw reads for sputum of L. pneumophila. Intravenous antibiotic therapy followed by azithromycin (80 mg every day) for 10 days. On day three of PICU admission, vasopressors were titrated off. Computed tomography scan of the chest disclosed decreased infiltrations over the both lung (Fig. 1 , B). The patient was extubated on the 5th day of PICU. Finally, after a 2-week stay in the PICU, her abnormal laboratory tests have returned to normal, and the patient recovered without any long-term sequelae. Case2 A five-year-old boy with Burkitt lymphoma was in the end of early chemotherapy. He was presented with multiple ulcers in oral mucosa for 10 days. Abnormal laboratory tests showed a WBC count of 0.16 × 10 9 /L with percentage of neutrophil 0.06%, hemoglobin 108 g/L (normal: 115–150 U/L) and a platelet count of 56 × 10 9 /L(normal: 125–350 U/L). He was admitted to the hospital because of the diagnosis of myelosuppression (Ⅳ °) and ulcerative stomatitis. On admission, the patient was in the state of tracheotomy. The WBC and percentage of neutrophils decreased significantly, empiric antibiotics with meropenem (500 mg every 8 h), sulfamethoxazole (400 mg Q6H) and trimethoprim (80 mg Q6H) and vancomycin (330 mg every 8 h) were administered for 6 days. On the 3th hospital day, the patient occurred fever, cough with yellow sputum at the tracheotomy. Widespread patchy infiltrations were seen in various segments of both lungs on computed tomography of the thorax (Fig. 2 , C). On the 5th hospital day, the respiratory symptoms of the patient gradually worsening. He was transferred to PICU. His physical examinations at PICU admission included: blood pressure of 87/53 mmHg (mean arterial pressure of 61.0 mmHg), a respiratory rate of 40 breaths/minute, a heart rate of 160 beats/minute, a temperature of 36.3℃, multiple ulcers in oral mucosa, rales on auscultation, low skin temperature of limbs and capillary refill time 5 seconds. Laboratory findings showed a WBC count of 0.14 × 10 9 /L with 0.21% neutrophil, hemoglobin 99 g/L and a platelet count of 39 × 10 9 /L, CRP 281.36 mg/dl, PCT49.34 ng/mL and interleukin-6 (IL-6) 19259.97 pg/mL (normal: 1.7–16.6 pg/mL). Arterial blood gas (ABG)showed a pH of 7.408 (normal:7.35–7.45), a pCO 2 level of 56.7 mmHg (normal: 35–45 mmHg), and a paO 2 level of 33.10 mmHg (normal: 80–100 mmHg), Lactate 2.52 mmol/L (normal: 0–2 mmol/L). The patient was diagnosed by severe sepsis with septic shock likely resulting from HAP. Aggressive intravenous fluids resuscitation and vasopressors (norepinephrine, vasopressin) were initiated on arrival to PICU. And he was complicated by respiratory distress so that he required mechanic ventilation. He was treated with CRRT to eliminate IL6 for 6 days. On the 6th hospital day, the patient suddenly developed ventricular fibrillation with cyanosis and weak heart sound. An oxygen saturation by pulse oximetry of 88% while mechanic ventilation fall to 60%. Blood pressure fall to 60/40 mmHg.He was treated with cardiopulmonary resuscitation and intermittent intravenous injections of 1:10000 adrenaline. He recovered after 15 minutes. Serum antibody, blood culture and respiratory culture were negative. We also sent samples of blood and sputum to BGI Group (Beijing, China) for mNGS. mNGS indicated Legionella pneumophila in blood and sputum. For blood, there was 2280 raw reads and 3372326 raw reads for sputum of L. pneumophila. He received Azithromycin (245 mg every day) therapy for 10 days. On the 12th hospital day, vasopressors were titrated off. On the 15th day of admission, chest radiography disclosed decreased infiltrations over the both lung (Fig. 2 , D). And the patient was extubated. On the 28th hospital day, he was transferred to general ward because of stable vital signs and normal laboratory examination. He had no discomfort follow up 2 months. Discussion And Conclusions In this report, we describe unusual cases of severe HAP and septic shock resulting from L. pneumophila. We identified L. pneumophila through mNGS of blood and sputum early in the course of illness. As we know, this is the first presentation of children with HAP and septic shock related to L. pneumophila infection in the English-language. Although authors have pointed out the importance of mNGS, especially in critically ill patients [ 5 ] , it is also the first report that patients with HAP and septic shock involved L. pneumophila were diagnosed by mNGS in children. HAP is a frequent complication of hospitalization. It has an assignable mortality rate of more than 8% [ 6 ] . The spectrum of causative organisms in HAP is more likely to involve gram-negative bacilli such as Pseudomonas aeruginosa or Staphylococcus aureus and Streptococcus pneumoniae in adults, not Legionella [ 7 ] . L. pneumophila can be isolated in HAP of immunocompromised adults, but Legionella pneumophila is rarely isolated in children [ 8 ] . Furthermore, culturing L. pneumophila requires a specific medium, which makes it difficult to obtain a positive result [ 9 , 4 ] . Therefore, it is difficult to identify bacteria when patients have sepsis and septic shock because of HAP [ 2 ] . Sepsis and septic shock are the main causes of childhood mortality all over the world. If doctors can conform pathogeny of sepsis, the mortality will decrease. As a result, pediatric doctors do not tend to systematically pursue diagnostic testing for L. pneumophila. Pediatric data from studies suggest that severe diseases of L. pneumophila occur in children with malignant neoplasms, organ transplantation, underlying pulmonary disease and immunosuppression with corticosteroids [ 10 – 12 ] . L. pneumophila belongs to Legionella which found in the environment, such as freshwater environments, moist soil and so on [ 13 ] . Human infection most commonly occurs as a result of contaminated manmade water sources, whirlpool spa humidifiers and evaporative condensers [ 13 ] . Generally, human infection is incidental and usually asymptomatic or mild and unrecognized. But individuals at higher risk for developing serious Legionnaires’ disease are olders, severe combined immune deficiency, cancer or organ transplantation [ 14 ] . Since the identification of L. pneumophila in 1977,research on adults indicates that the incidence rate is up to 1.4 case notifications per 100,000 individuals [ 15 ] . Over decades, L. pneumophila infection has been reported increasingly in immunocompromised patients, but our understanding of its epidemiology depends on case reports [ 16 ] . A patient with L. pneumophila infection shows pneumonic as well as a variety of extrapulmonary manifestations, such as headache, encephalopathy, relative bradycardia, abdominal pain, hepatic involvement, electrolyte imbalance and other multisystemic findings [ 17 ] . Severe extrapulmonary findings of L. pneumophila infection are rare, especially in children [ 18 ] . In this report, our patients presented with HAP and septic shock resulting from L. pneumophila. Review the literature, extrapulmonary findings involved sepsis and septic shock are few in adults [ 19 – 22 ] . The clinical data of patients with sepsis and septic shock related to L. pneumophila are depicted in Table 1 . There are four patients in total who are adults who are mostly olders with chronic disease or bad habits. They had sepsis and septic shock along with respiratory symptoms or pneumonia. The primary antibiotics for L. pneumophila infection are quinolones or beta-lactam therapy. In this paper, our immunocompromised patients had liver transplantation or lymphadenoma. They had higher risk for developing severe Legionnaires’ disease. We chose azithromycin as the main antibiotic treatment. In addition, we take advantage of CRRT to remove inflammatory mediators, as well as improving circulation and clinical manifestations. The advantages of CRRT for sepsis and sepsis shock have been reported in the literature [ 23 ] . For L. pneumophila infection, the time to detection is still crucial for the final outcome of the disease, especially for at-high-risk populations. In addition to clinical manifestations, laboratory tests are also essential for diagnosis; therefore, specific detection methods include serological and antibody-based detection, culture, urine antigen detection and nucleic acid amplification detection [ 4 ] . These methods have been developed to evaluate L. pneumophila using sputum or respiratory secretions, blood or tissue, urine or serum samples [ 4 ] . However, culture on a prescribed growth medium is still the standard reference method for the diagnosis and identification of L. pneumophila, it is very difficult to isolate bacteria from samples [ 4 ] . mNGS is a high-throughput pathogen identification method, which is superior to the existing microbial diagnosis methods in the identification of culturable pathogens [ 24 ] . From Table 1 , there were many ways to detect pathogeny; the positive rate of blood culture was very low. In this report, polymerase chain reaction (PCR) and serologic testing were performed as well as culture of blood and sputum at PICU admission. And there was a negative consequence. We sent samples of blood and sputum for mNGS just as described in the literature [ 5 ] . Finally, we identified the presence of L. pneumophila with the help of mNGS. Under azithromycin treatment, the patients recovered at last. Taken together, sepsis or sepsis shock caused by L. pneumophila is rare, especially in children. The detection time of pathogen is very important at high-risk population. mNGS is useful for conforming hard-to-culture pathogens, and it has short turnaround time. Therefore, it is useful for severely ill patients especially. It is sensitive but expensive, so doctors must assess the value of mNGS for identifying pathogens. In a few words, pediatric physicians should be aware that L. pneumophila can cause 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. Abbreviations PICU Pediatric intensive care unit L. pneumophila Legionella pneumophila HAP Hospital-acquired pneumonia mNGS Metagenomics next-generation sequencing ALT Alanine aminotransferase AST Aspartate aminotransferase WBC White blood cell CRP C-reactive protein PCT Procalcitonin CRRT Continuous renal replacement therapy IL-6 Interleukin-6 PCR Polymerase chain reaction COPD Chronic obstructive pulmonary disease BALF Bronchoalveolar lavage fluid Declarations Ethics approval and consent to participate Not applicable. Consent for publication We obtained the written consent for publication from the guardian of the patient. Availability of data and materials The data used in this report are available from the corresponding author on reasonable request. Competing interests All authors have no conflicts of interest to declare for this work. Funding Not applicable. Authors’ contributions All authors contributed to the intellectual content of this manuscript and approved the final manuscript as submitted. MD drafted the initial manuscript. MD and CY interpreted the data. YL revised the article critically for important intellectual content. Acknowledgments Not applicable. References Tan B, Wong JJ, Sultana R, et al. Global case-fatality rates in pediatric severe sepsis and septic shock: a systematic review and meta-analysis. JAMA Pediatr.2019. Schlapbach LJ, Straney L, Alexander J, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13: a multicentre retrospective cohort study. Lancet Infect Dis. 2015; 15:46–54. Weiss SL, Fitzgerald JC, Pappachan J, et al., Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015; 191:1147–1157. Dunne WM, Picot N, van Belkum A. Laboratory tests for Legionnaire’ s disease. Infect Dis Clin North Am. 2017;31(1):167–78. Huahua Yi, Jie Fang, Jingwen Huang, et al. Legionella pneumophila as Cause of Severe Community-Acquired Pneumonia, China. Emerg Infect Dis.2020 Jan;26(1):160-162. Wolkewitz M et al. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care. 2008;12(2): R44. Weber DJ, Sickbert-Bennett EE, Brown V , et al. Comparison of hospitalwide surveillance and targeted intensive care unit surveillance of healthcare-associated infections. Infect Control Hosp Epidemiol.2007;28(12):1361–6. Diederen BM. Legionella spp. and Legionnaires’ disease. J Infect. 2008; 56:1–12. Mercante JW, Winchell JM. Current and emerging Legionella diagnostics for laboratory and outbreak investigations. Clin Microbiol Rev. 2015;28(1):95–133. Rotem Lapidot, Laila Alawdah, J R Köhler,et al. Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency. Pediatr Infect Dis J. 2018 Apr;37(4):356-358. Ivan A Gonzalez, Judith M Martin. Legionella pneumophilia serogroup 1 pneumonia recurrence postbone marrow transplantation. Pediatr Infect Dis J. 2007 Oct;26(10):961-3. Yael Shachor-Meyouhas, Sarit Ravid , Suheir Hanna,et al. Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone. J Pediatr.2017 Jul;186:186-188.e1. Newton HJ, Ang DKY, van Driel IR, et al. Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev. 2010;23(2):274–98. Cunha CB, Cunha BA. Legionnaire’ s disease since Philadelphia: lessons learned and continued progress. Infect Dis Clin North Am. 2017;31(1):1–5 Sonia Mondino, Silke Schmidt , Monica Rolando,et al. Legionnaires’ Disease: State of the Art Knowledge of Pathogenesis Mechanisms of Legionella. Annu Rev Pathol.2020 Jan 24;15:439-466. Neil K, Berkelman R. Increasing incidence of legionellosis in the United States, 1990-2005: changing epidemiologic trends. Clin Infect Dis.2008;47:591-9. Cunha BA. Legionnaires’ disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am. 2010;24(1):73–105. Rotem Lapidot, Laila Alawdah, J R Köhler ,et al. Hepatic Legionella pneumophila Infection in an Infant with Severe Combined Immunodeficiency. Pediatr Infect Dis J.2018 Apr;37(4):356-358. Jose Orsini, Brendan J Frawley, Hannah Gawlak, et al. Severe Sepsis With Septic Shock as a Consequence of a Severe Community-Acquired Pneumonia Resulting From a Combined Legionella pneumophila and Streptococcus pneumoniae Infection. Cureus. 2020 Oct 15;12(10):e10966. Florence Grattard, Séverine Allegra, Jerome Morel,et al. Septic shock due to Legionella pneumophila serogroup 2:usefulness of molecular biology for diagnosis, treatment and epidemiological investigation. Intensive Care Med. 2010 Aug;36(8):1439-40. C-C Lai, C-K Tan, C-H Chou, et al. Hospital-Acquired Pneumonia and Bacteremia Caused by Legionella pneumophila in an Immunocompromised Patient.Infection. 2010 Apr;38(2):135-7. TF Marrie, RS Martin, et al. Persistent Legionella pneumophila bacteraemia in an immunocompromised host. J Infect. 1988 Mar;16(2):203-4. Ayman Karkar, Claudio Ronco. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care. 2020 Mar 6;10(1):32. Sophia Yohe, Bharat Thyagarajan. Review of Clinical Next-Generation Sequencing. Arch Pathol Lab Med. 2017 Nov;141(11):1544-1557. Table Table 1 The clinical data of patients with sepsis and septic shock related to Legionella infection. No Age (years) Sex Medical history Etiology Diagnosis and follow-up of Legionella infection in anti- infectious treatment Date Authors Sample Technique Result 1 65 Male systemic arterial hypertension, dyslipidemia, COPD dyspnea Blood Tracheal aspirate Urine Culture PCR Culture Immunochro- matographic assay Negative Negative Negative Positive Azithromycin 2020 Jose, et al [ 19 ] 2 48 Female Smoking Fever, cough Tracheal aspirate Blood 16rDNA PCR Rapid antigen test Positive Negative —— 2010 Florence, et al [ 20 ] 3 64 Female hypertension Multiple purpura, Thrombocytopenia Blood Urine Culture Indirect immu- nofluorescence 16rDNA PCR immuno-chromaographic assay and enzyme immunoassay Negative Positive Positive Positive Ciprofloxacin 2010 C.-C. Lai,et al [ 21 ] 4 66 Female None Fever, myalgia Blood BALF Culture direct immuno- flourescence Positive Positive Erythromycin 1988 TF Marrie, et al [ 22 ] COPD, chronic obstructive pulmonary disease; PCR, polymerase chain reaction; BALF, bronchoalveolar lavage fluid. Supplementary Files CAREchecklist.pdf CAREchecklist.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-122218","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case report","associatedPublications":[],"authors":[{"id":5898874,"identity":"b85a41a1-3011-425a-b5db-a70c79eaaaf6","order_by":0,"name":"Min Ding","email":"","orcid":"","institution":"Jilin University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Ding","suffix":""},{"id":5898875,"identity":"e86da02e-fff3-497f-910e-22d9ee421ec5","order_by":1,"name":"Chunfeng Yang","email":"","orcid":"","institution":"Jilin University First Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chunfeng","middleName":"","lastName":"Yang","suffix":""},{"id":5898876,"identity":"266abcc1-bfc4-4cfd-a6ef-573b956ce752","order_by":2,"name":"Yu-mei Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArElEQVRIiWNgGAWjYHACxgMJFWwyIJYE0XoOJJxh4yFRC2MbAwlaDK4dYDjwcB4fj8EB5oO3eRjs8ghruZ3AcCBxGxtQC1uyNQ9DcjEpWnjMpHmA7AbitMwBaeH/RoqWBrAtbMRpkQRpSTjGxiN5mM3Yco5BMmEtfLcTGB/+qDkmx3e8+eGNNxV2hLUoHOD/AKSOMTAwg91JSD0QyEMMrSFC6SgYBaNgFIxYAACkizpmIiJb5gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-7705-4950","institution":"Jilin University First Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yu-mei","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2020-12-04 23:59:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-122218/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-122218/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4176213,"identity":"ea0252b9-d96f-48d4-bf45-9ba7cda34f34","added_by":"auto","created_at":"2020-12-10 21:17:28","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22026,"visible":true,"origin":"","legend":"Computed tomography scan of the chest in case1.(A) It showed patchy infiltrations were seen in the upper lobe of right lung and lower lobe of left lung.(B) It disclosed decreased infiltrations over the both lung.","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/ee5feec7c7279139904c0bdf.jpg"},{"id":4176209,"identity":"e200e5f4-f02d-47f9-abee-e0cc6c38ae7c","added_by":"auto","created_at":"2020-12-10 21:17:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22026,"visible":true,"origin":"","legend":"Computed tomography scan of the chest in case1.(A) It showed patchy infiltrations were seen in the upper lobe of right lung and lower lobe of left lung.(B) It disclosed decreased infiltrations over the both lung.","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/8675ddc91f97215a29493d18.jpg"},{"id":4176214,"identity":"3bc2e7d4-b2e1-412d-bb91-1e025a8b8cb6","added_by":"auto","created_at":"2020-12-10 21:17:29","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26308,"visible":true,"origin":"","legend":"Computed tomography scan of the chest in case2. (C) Widespread patchy infiltrations were seen in various segments of both lungs on computed tomography of the thorax. (D) It disclosed decreased infiltrations over the both lung.","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/4ccf527764b24047ae704b1a.jpg"},{"id":4176210,"identity":"41e21080-aa5e-4a45-be71-b79fe162c59e","added_by":"auto","created_at":"2020-12-10 21:17:22","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26308,"visible":true,"origin":"","legend":"Computed tomography scan of the chest in case2. (C) Widespread patchy infiltrations were seen in various segments of both lungs on computed tomography of the thorax. (D) It disclosed decreased infiltrations over the both lung.","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/64e72653acb9bad01fac1ca6.jpg"},{"id":13632099,"identity":"528c2b49-9d1b-4b38-843e-8ac2a6906e6e","added_by":"auto","created_at":"2021-09-17 08:19:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":322425,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/b000dc80-230f-4516-8bda-f8d5b28fa481.pdf"},{"id":4176215,"identity":"5575ad90-b3df-49ea-821b-3ca837680d2d","added_by":"auto","created_at":"2020-12-10 21:17:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":742178,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/7d454f4cbcaeb501d9d4f1fd.pdf"},{"id":4176211,"identity":"067bca1e-626f-4896-93b2-3e09883ee0fd","added_by":"auto","created_at":"2020-12-10 21:17:23","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":742178,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-122218/v1/6465ff534f4869c6f52ea162.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eSevere 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\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eSepsis is the leading causes of childhood mortality worldwide and identified a highest mortality of 22.8% in developing countries \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Although studies demonstrate the impact of staphylococcal and streptococcal infections as leading pathogens for sepsis, only approximatively 50% children admitted to pediatric intensive care unit (PICU) with a clinical diagnosis of sepsis have a microbiologically confirmed infection \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Because the majority of pediatric sepsis befall very early, it is very important to identify the pathogen as soon as possible \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Legionella pneumophila (L. pneumophila) is an important pathogen of severe pneumonia in immunocompromised patients. It also can occur extrapulmonary manifestations. L. pneumophila in patients is difficult to identified because of nonspecific clinical symptoms. Although a variety of methods have been developed to detect L. pneumophila, it is still difficult to isolate it from blood as the gold standard \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. As far as we know, reports about L. pneumophila with sepsis or septic shock in children are extremely rare. We describe 2 children who had severe sepsis with septic shock as a consequence of a severe hospital-acquired pneumonia (HAP) resulting from L. pneumophila. We verified L. pneumophila infection through metagenomics next-generation sequencing (mNGS) of blood and sputum. This is the first presentation of children with septic shock related to L. pneumophila infection diagnosed by mNGS in the English-language. It is important to remind pediatricians that it does occur in children, particularly in immunocompromised patients. And it is useful that we can verified pathogeny by mNGS for critically ill patients in the early course of illness.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003e\u003cstrong\u003eCase1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA six-month girl with congenital biliary atresia underwent liver transplantation. Engraftment on day 28 posttransplant was complicated by an increased alanine aminotransferase (ALT) level. She had no fever, cough and other symptoms while at home. She was suspected for rejecting the liver and admitted to hospital. On admission, her immunosuppression included tacrolimus (1.2\u0026nbsp;mg every 12 h)and methylprednisolone (12\u0026nbsp;mg every day).Her abnormal laboratory results included an ALT level of 283\u0026nbsp;U/L (normal: 7\u0026ndash;40\u0026nbsp;U/L) and an aspartate aminotransferase (AST) level of 112.7\u0026nbsp;U/L (normal: 13\u0026ndash;35\u0026nbsp;U/L). Empiric intravenous therapy with high-dose methylprednisolone( 80\u0026nbsp;mg intravenously every day) was initiated, along with oral tacrolimus continuously (1.2\u0026nbsp;mg every 12 h).Her ALT and AST were decreased gradually during hospitalization.\u003c/p\u003e\n\u003cp\u003eOn the 25th hospital day, she presented with fever, cough with whitish sputum, and shortness of breath. Coarse crackles were heard over both lung fields. Laboratory data revealed a white blood cell(WBC) count of 25.45\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L with neutrophil predominance (79%)(normal: 4\u0026ndash;10\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L), C-reactive protein(CRP) 51.26\u0026nbsp;mg/dl (normal: 0-3.5\u0026nbsp;U/L)and procalcitonin(PCT) 0.22\u0026nbsp;ng/mL(normal: 0-0.1\u0026nbsp;U/L). Computed tomography scan of the chest showed patchy infiltrations were seen in the upper lobe of right lung and lower lobe of left lung (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, A). After the culture of blood and sputum, empiric antibiotics with meropenem (80\u0026nbsp;mg every 8\u0026nbsp;h), micafunginand (30\u0026nbsp;mg every day) and vancomycin (160\u0026nbsp;mg every 12\u0026nbsp;h) were administered for 6 days. Pathogenic serological and antibody-based assays, blood culture and respiratory culture were negative.\u003c/p\u003e\n\u003cp\u003eOn the 31th admission, the patient needed mechanic ventilation because of worsening dyspnea. She was transferred to PICU. Her vital signs on arrival to PICU were as follows: blood pressure of 80/33\u0026nbsp;mmHg (mean arterial pressure of 48.7\u0026nbsp;mmHg), a respiratory rate of 50 breaths/minute, a heart rate of 240 beats/minute, a temperature of 38.3℃, and an oxygen saturation by pulse oximetry of 85% while breathing ambient air. Physical examination revealed with rales on auscultation, low skin temperature of limbs and capillary refill time 3 seconds. After a critical care medicine evaluation was requested, the patient was diagnosed by severe sepsis with septic shock likely resulting from HAP. Aggressive intravenous fluids resuscitation and vasopressors (norepinephrine, vasopressin) were initiated on arrival to PICU, and the patient was subsequently intubated and placed on mechanical ventilation because of worsening tachypnea and increased FiO\u003csub\u003e2\u003c/sub\u003e requirements. Meanwhile, she was treated with continuous renal replacement therapy (CRRT) to eliminate inflammatory factors for 2 days. Empiric antibiotics with meropenem (370\u0026nbsp;mg every 8\u0026nbsp;h), caspofungin (30\u0026nbsp;mg every day) and vancomycin (140\u0026nbsp;mg every 8\u0026nbsp;h) were continued to be administered, along with oral tacrolimus and methylprednisolone.\u003c/p\u003e\n\u003cp\u003eWe sent samples of blood and sputum to BGI Group (Beijing, China) for mNGS. Though Serum antibody, blood culture and respiratory culture were negative, mNGS indicated L. pneumophila in blood and sputum. For blood, there was 1044 raw reads and 516 raw reads for sputum of L. pneumophila. Intravenous antibiotic therapy followed by azithromycin (80\u0026nbsp;mg every day) for 10 days. On day three of PICU admission, vasopressors were titrated off. Computed tomography scan of the chest disclosed decreased infiltrations over the both lung (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, B). The patient was extubated on the 5th day of PICU. Finally, after a 2-week stay in the PICU, her abnormal laboratory tests have returned to normal, and the patient recovered without any long-term sequelae.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA five-year-old boy with Burkitt lymphoma was in the end of early chemotherapy. He was presented with multiple ulcers in oral mucosa for 10\u0026nbsp;days. Abnormal laboratory tests showed a WBC count of 0.16\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L with percentage of neutrophil 0.06%, hemoglobin 108\u0026nbsp;g/L (normal: 115\u0026ndash;150\u0026nbsp;U/L) and a platelet count of 56\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L(normal: 125\u0026ndash;350\u0026nbsp;U/L). He was admitted to the hospital because of the diagnosis of myelosuppression (Ⅳ \u0026deg;) and ulcerative stomatitis. On admission, the patient was in the state of tracheotomy. The WBC and percentage of neutrophils decreased significantly, empiric antibiotics with meropenem (500\u0026nbsp;mg every 8\u0026nbsp;h), sulfamethoxazole (400\u0026nbsp;mg Q6H) and trimethoprim (80\u0026nbsp;mg Q6H) and vancomycin (330\u0026nbsp;mg every 8\u0026nbsp;h) were administered for 6\u0026nbsp;days.\u003c/p\u003e\n\u003cp\u003eOn the 3th hospital day, the patient occurred fever, cough with yellow sputum at the tracheotomy. Widespread patchy infiltrations were seen in various segments of both lungs on computed tomography of the thorax (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, C). On the 5th hospital day, the respiratory symptoms of the patient gradually worsening. He was transferred to PICU. His physical examinations at PICU admission included: blood pressure of 87/53\u0026nbsp;mmHg (mean arterial pressure of 61.0\u0026nbsp;mmHg), a respiratory rate of 40 breaths/minute, a heart rate of 160 beats/minute, a temperature of 36.3℃, multiple ulcers in oral mucosa, rales on auscultation, low skin temperature of limbs and capillary refill time 5 seconds. Laboratory findings showed a WBC count of 0.14\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L with 0.21% neutrophil, hemoglobin 99\u0026nbsp;g/L and a platelet count of 39\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L, CRP 281.36\u0026nbsp;mg/dl, PCT49.34\u0026nbsp;ng/mL and interleukin-6 (IL-6) 19259.97\u0026nbsp;pg/mL (normal: 1.7\u0026ndash;16.6\u0026nbsp;pg/mL). Arterial blood gas (ABG)showed a pH of 7.408 (normal:7.35\u0026ndash;7.45), a pCO\u003csub\u003e2\u003c/sub\u003e level of 56.7\u0026nbsp;mmHg (normal: 35\u0026ndash;45\u0026nbsp;mmHg), and a paO\u003csub\u003e2\u003c/sub\u003e level of 33.10\u0026nbsp;mmHg (normal: 80\u0026ndash;100\u0026nbsp;mmHg), Lactate 2.52\u0026nbsp;mmol/L (normal: 0\u0026ndash;2\u0026nbsp;mmol/L). The patient was diagnosed by severe sepsis with septic shock likely resulting from HAP. Aggressive intravenous fluids resuscitation and vasopressors (norepinephrine, vasopressin) were initiated on arrival to PICU. And he was complicated by respiratory distress so that he required mechanic ventilation. He was treated with CRRT to eliminate IL6 for 6 days. On the 6th hospital day, the patient suddenly developed ventricular fibrillation with cyanosis and weak heart sound. An oxygen saturation by pulse oximetry of 88% while mechanic ventilation fall to 60%. Blood pressure fall to 60/40\u0026nbsp;mmHg.He was treated with cardiopulmonary resuscitation and intermittent intravenous injections of 1:10000 adrenaline. He recovered after 15 minutes. Serum antibody, blood culture and respiratory culture were negative.\u003c/p\u003e\n\u003cp\u003eWe also sent samples of blood and sputum to BGI Group (Beijing, China) for mNGS. mNGS indicated Legionella pneumophila in blood and sputum. For blood, there was 2280 raw reads and 3372326 raw reads for sputum of L. pneumophila. He received Azithromycin (245\u0026nbsp;mg every day) therapy for 10 days. On the 12th hospital day, vasopressors were titrated off. On the 15th day of admission, chest radiography disclosed decreased infiltrations over the both lung (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, D). And the patient was extubated. On the 28th hospital day, he was transferred to general ward because of stable vital signs and normal laboratory examination. He had no discomfort follow up 2 months.\u003c/p\u003e"},{"header":"Discussion And Conclusions ","content":"\u003cp\u003eIn this report, we describe unusual cases of severe HAP and septic shock resulting from L. pneumophila. We identified L. pneumophila through mNGS of blood and sputum early in the course of illness. As we know, this is the first presentation of children with HAP and septic shock related to L. pneumophila infection in the English-language. Although authors have pointed out the importance of mNGS, especially in critically ill patients \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, it is also the first report that patients with HAP and septic shock involved L. pneumophila were diagnosed by mNGS in children.\u003c/p\u003e\n\u003cp\u003eHAP is a frequent complication of hospitalization. It has an assignable mortality rate of more than 8% \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. The spectrum of causative organisms in HAP is more likely to involve gram-negative bacilli such as Pseudomonas aeruginosa or Staphylococcus aureus and Streptococcus pneumoniae in adults, not Legionella \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. L. pneumophila can be isolated in HAP of immunocompromised adults, but Legionella pneumophila is rarely isolated in children \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Furthermore, culturing L. pneumophila requires a specific medium, which makes it difficult to obtain a positive result \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Therefore, it is difficult to identify bacteria when patients have sepsis and septic shock because of HAP \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Sepsis and septic shock are the main causes of childhood mortality all over the world. If doctors can conform pathogeny of sepsis, the mortality will decrease. As a result, pediatric doctors do not tend to systematically pursue diagnostic testing for L. pneumophila. Pediatric data from studies suggest that severe diseases of L. pneumophila occur in children with malignant neoplasms, organ transplantation, underlying pulmonary disease and immunosuppression with corticosteroids \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eL. pneumophila belongs to Legionella which found in the environment, such as freshwater environments, moist soil and so on \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Human infection most commonly occurs as a result of contaminated manmade water sources, whirlpool spa humidifiers and evaporative condensers \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Generally, human infection is incidental and usually asymptomatic or mild and unrecognized. But individuals at higher risk for developing serious Legionnaires\u0026rsquo; disease are olders, severe combined immune deficiency, cancer or organ transplantation \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Since the identification of L. pneumophila in 1977,research on adults indicates that the incidence rate is up to 1.4 case notifications per 100,000 individuals \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Over decades, L. pneumophila infection has been reported increasingly in immunocompromised patients, but our understanding of its epidemiology depends on case reports \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. A patient with L. pneumophila infection shows pneumonic as well as a variety of extrapulmonary manifestations, such as headache, encephalopathy, relative bradycardia, abdominal pain, hepatic involvement, electrolyte imbalance and other multisystemic findings \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Severe extrapulmonary findings of L. pneumophila infection are rare, especially in children \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn this report, our patients presented with HAP and septic shock resulting from L. pneumophila. Review the literature, extrapulmonary findings involved sepsis and septic shock are few in adults \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. The clinical data of patients with sepsis and septic shock related to L. pneumophila are depicted in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. There are four patients in total who are adults who are mostly olders with chronic disease or bad habits. They had sepsis and septic shock along with respiratory symptoms or pneumonia. The primary antibiotics for L. pneumophila infection are quinolones or beta-lactam therapy. In this paper, our immunocompromised patients had liver transplantation or lymphadenoma. They had higher risk for developing severe Legionnaires\u0026rsquo; disease. We chose azithromycin as the main antibiotic treatment. In addition, we take advantage of CRRT to remove inflammatory mediators, as well as improving circulation and clinical manifestations. The advantages of CRRT for sepsis and sepsis shock have been reported in the literature \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFor L. pneumophila infection, the time to detection is still crucial for the final outcome of the disease, especially for at-high-risk populations. In addition to clinical manifestations, laboratory tests are also essential for diagnosis; therefore, specific detection methods include serological and antibody-based detection, culture, urine antigen detection and nucleic acid amplification detection \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. These methods have been developed to evaluate L. pneumophila using sputum or respiratory secretions, blood or tissue, urine or serum samples \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. However, culture on a prescribed growth medium is still the standard reference method for the diagnosis and identification of L. pneumophila, it is very difficult to isolate bacteria from samples \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. mNGS is a high-throughput pathogen identification method, which is superior to the existing microbial diagnosis methods in the identification of culturable pathogens \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. From Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, there were many ways to detect pathogeny; the positive rate of blood culture was very low. In this report, polymerase chain reaction (PCR) and serologic testing were performed as well as culture of blood and sputum at PICU admission. And there was a negative consequence. We sent samples of blood and sputum for mNGS just as described in the literature \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Finally, we identified the presence of L. pneumophila with the help of mNGS. Under azithromycin treatment, the patients recovered at last.\u003c/p\u003e\n\u003cp\u003eTaken together, sepsis or sepsis shock caused by L. pneumophila is rare, especially in children. The detection time of pathogen is very important at high-risk population. mNGS is useful for conforming hard-to-culture pathogens, and it has short turnaround time. Therefore, it is useful for severely ill patients especially. It is sensitive but expensive, so doctors must assess the value of mNGS for identifying pathogens. In a few words, pediatric physicians should be aware that L. pneumophila can cause 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.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePICU Pediatric intensive care unit\u003c/p\u003e\n\u003cp\u003eL. pneumophila Legionella pneumophila\u003c/p\u003e\n\u003cp\u003eHAP Hospital-acquired pneumonia\u003c/p\u003e\n\u003cp\u003emNGS Metagenomics next-generation sequencing\u003c/p\u003e\n\u003cp\u003eALT Alanine aminotransferase\u003c/p\u003e\n\u003cp\u003eAST Aspartate aminotransferase\u003c/p\u003e\n\u003cp\u003eWBC White blood cell\u003c/p\u003e\n\u003cp\u003eCRP C-reactive protein\u003c/p\u003e\n\u003cp\u003ePCT Procalcitonin\u003c/p\u003e\n\u003cp\u003eCRRT Continuous renal replacement therapy\u003c/p\u003e\n\u003cp\u003eIL-6 Interleukin-6\u003c/p\u003e\n\u003cp\u003ePCR Polymerase chain reaction\u003c/p\u003e\n\u003cp\u003eCOPD Chronic obstructive pulmonary disease\u003c/p\u003e\n\u003cp\u003eBALF Bronchoalveolar lavage fluid\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe obtained the written consent for publication from the guardian of the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used in this report are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have no conflicts of interest to declare for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the intellectual content of this manuscript and approved the final manuscript as submitted. MD drafted the initial manuscript. MD and CY interpreted the data. YL revised the article critically for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTan B, Wong JJ, Sultana R, et al. Global case-fatality rates in pediatric severe sepsis and septic shock: a systematic review and meta-analysis. JAMA Pediatr.2019.\u003c/li\u003e\n\u003cli\u003eSchlapbach LJ, Straney L, Alexander J, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13: a multicentre retrospective cohort study. Lancet Infect Dis. 2015; 15:46\u0026ndash;54.\u003c/li\u003e\n\u003cli\u003eWeiss SL, Fitzgerald JC, Pappachan J, et al., Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015; 191:1147\u0026ndash;1157.\u003c/li\u003e\n\u003cli\u003eDunne WM, Picot N, van Belkum A. Laboratory tests for Legionnaire\u0026rsquo; s disease. Infect Dis Clin North Am. 2017;31(1):167\u0026ndash;78.\u003c/li\u003e\n\u003cli\u003eHuahua Yi, Jie Fang, Jingwen Huang, et al. Legionella pneumophila as Cause of Severe Community-Acquired Pneumonia, China. Emerg Infect Dis.2020 Jan;26(1):160-162.\u003c/li\u003e\n\u003cli\u003eWolkewitz M et al. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care. 2008;12(2): R44.\u003c/li\u003e\n\u003cli\u003eWeber DJ, Sickbert-Bennett EE, Brown V , et al. Comparison of hospitalwide surveillance and targeted intensive care unit surveillance of healthcare-associated infections. Infect Control Hosp Epidemiol.2007;28(12):1361\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eDiederen BM. Legionella spp. and Legionnaires\u0026rsquo; disease. J Infect. 2008; 56:1\u0026ndash;12.\u003c/li\u003e\n\u003cli\u003eMercante JW, Winchell JM. Current and emerging Legionella diagnostics for laboratory and outbreak investigations. Clin Microbiol Rev. 2015;28(1):95\u0026ndash;133.\u003c/li\u003e\n\u003cli\u003eRotem Lapidot, Laila Alawdah, J R K\u0026ouml;hler,et al. Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency. Pediatr Infect Dis J. 2018 Apr;37(4):356-358.\u003c/li\u003e\n\u003cli\u003eIvan A Gonzalez, Judith M Martin. Legionella pneumophilia serogroup 1 pneumonia recurrence postbone marrow transplantation. Pediatr Infect Dis J. 2007 Oct;26(10):961-3.\u003c/li\u003e\n\u003cli\u003eYael Shachor-Meyouhas, Sarit Ravid , Suheir Hanna,et al. Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone. J Pediatr.2017 Jul;186:186-188.e1.\u003c/li\u003e\n\u003cli\u003eNewton HJ, Ang DKY, van Driel IR, et al. Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev. 2010;23(2):274\u0026ndash;98.\u003c/li\u003e\n\u003cli\u003eCunha CB, Cunha BA. Legionnaire\u0026rsquo; s disease since Philadelphia: lessons learned and continued progress. Infect Dis Clin North Am. 2017;31(1):1\u0026ndash;5\u003c/li\u003e\n\u003cli\u003eSonia Mondino, Silke Schmidt , Monica Rolando,et al. Legionnaires\u0026rsquo; Disease: State of the Art Knowledge of Pathogenesis Mechanisms of Legionella. Annu Rev Pathol.2020 Jan 24;15:439-466.\u003c/li\u003e\n\u003cli\u003eNeil K, Berkelman R. Increasing incidence of legionellosis in the United States, 1990-2005: changing epidemiologic trends. Clin Infect Dis.2008;47:591-9.\u003c/li\u003e\n\u003cli\u003eCunha BA. Legionnaires\u0026rsquo; disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am. 2010;24(1):73\u0026ndash;105.\u003c/li\u003e\n\u003cli\u003eRotem Lapidot, Laila Alawdah, J R K\u0026ouml;hler ,et al. Hepatic Legionella pneumophila Infection in an Infant with Severe Combined Immunodeficiency. Pediatr Infect Dis J.2018 Apr;37(4):356-358.\u003c/li\u003e\n\u003cli\u003eJose Orsini, Brendan J Frawley, Hannah Gawlak, et al. Severe Sepsis With Septic Shock as a Consequence of a Severe Community-Acquired Pneumonia Resulting From a Combined Legionella pneumophila and Streptococcus pneumoniae Infection. Cureus. 2020 Oct 15;12(10):e10966.\u003c/li\u003e\n\u003cli\u003eFlorence Grattard, S\u0026eacute;verine Allegra, Jerome Morel,et al. Septic shock due to Legionella pneumophila serogroup 2:usefulness of molecular biology for diagnosis, treatment and epidemiological investigation. Intensive Care Med. 2010 Aug;36(8):1439-40.\u003c/li\u003e\n\u003cli\u003eC-C Lai, C-K Tan, C-H Chou, et al. Hospital-Acquired Pneumonia and Bacteremia Caused by Legionella pneumophila in an Immunocompromised Patient.Infection. 2010 Apr;38(2):135-7.\u003c/li\u003e\n\u003cli\u003eTF Marrie, RS Martin, et al. Persistent Legionella pneumophila bacteraemia in an immunocompromised host. J Infect. 1988 Mar;16(2):203-4.\u003c/li\u003e\n\u003cli\u003eAyman Karkar, Claudio Ronco. Prescription of CRRT: a pathway to optimize therapy. Ann Intensive Care. 2020 Mar 6;10(1):32.\u003c/li\u003e\n\u003cli\u003eSophia Yohe, Bharat Thyagarajan. Review of Clinical Next-Generation Sequencing. Arch Pathol Lab Med. 2017 Nov;141(11):1544-1557.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe clinical data of patients with sepsis and septic shock related to Legionella infection.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMedical history\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEtiology\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eDiagnosis and follow-up of Legionella infection\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ein anti-\u003c/p\u003e\n\u003cp\u003einfectious treatment\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDate\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAuthors\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSample\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTechnique\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eResult\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003esystemic arterial hypertension, dyslipidemia, COPD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003edyspnea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood\u003c/p\u003e\n\u003cp\u003eTracheal aspirate\u003c/p\u003e\n\u003cp\u003eUrine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCulture\u003c/p\u003e\n\u003cp\u003ePCR\u003c/p\u003e\n\u003cp\u003eCulture\u003c/p\u003e\n\u003cp\u003eImmunochro-\u003c/p\u003e\n\u003cp\u003ematographic assay\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAzithromycin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJose, et al \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSmoking\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFever, cough\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTracheal aspirate\u003c/p\u003e\n\u003cp\u003eBlood\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16rDNA PCR\u003c/p\u003e\n\u003cp\u003eRapid antigen test\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026mdash;\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFlorence, et al \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ehypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMultiple purpura, Thrombocytopenia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood\u003c/p\u003e\n\u003cp\u003eUrine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCulture\u003c/p\u003e\n\u003cp\u003eIndirect immu- nofluorescence\u003c/p\u003e\n\u003cp\u003e16rDNA PCR\u003c/p\u003e\n\u003cp\u003eimmuno-chromaographic assay and enzyme immunoassay\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative Positive\u003c/p\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCiprofloxacin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eC.-C. Lai,et al \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFever, myalgia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood\u003c/p\u003e\n\u003cp\u003eBALF\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCulture\u003c/p\u003e\n\u003cp\u003edirect immuno- flourescence\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eErythromycin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1988\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTF Marrie, et al \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003eCOPD, chronic obstructive pulmonary disease; PCR, polymerase chain reaction; BALF, bronchoalveolar lavage fluid.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Legionella pneumophila, sepsis shock, metagenomics next-generation sequencing","lastPublishedDoi":"10.21203/rs.3.rs-122218/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-122218/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\u003cp\u003eLegionella 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.\u003c/p\u003e\u003cp\u003eCase presentation\u003c/p\u003e\u003cp\u003eThere 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.\u003c/p\u003e\u003cp\u003eConclusions\u003c/p\u003e\u003cp\u003eThough 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.\u003c/p\u003e","manuscriptTitle":"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","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-10 21:17:21","doi":"10.21203/rs.3.rs-122218/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"370ee00a-9d46-4214-bf36-3129b855386c","owner":[],"postedDate":"December 10th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1396635,"name":"Pediatrics"}],"tags":[],"updatedAt":"2020-12-20T12:20:35+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-10 21:17:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-122218","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-122218","identity":"rs-122218","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}