Metagenomic next-generation sequencing reveals co-infection with Legionella pneumophila and Fusobacterium necrophorum in a patient with severe pneumonia: a case report.

BACKGROUND: Legionella pneumonia is one of the most severe types of atypical pneumonia, impairing multiple organ systems, posing a threat to life. Diagnosing Legionella pneumonia is challenging due to difficulties in culturing the bacteria and limitations in immunoassay sensitivity and specificity. CASE PRESENTATION: This paper reports a rare case of sepsis caused by combined infection with Legionella pneumophila and Fusobacterium necrophorum, leading to respiratory failure, acute kidney injury, acute liver injury, myocardial damage, and electrolyte disorders. In addition, we systematically reviewed literature on patients with combined Legionella infections, analyzing their clinical features, laboratory results and diagnosis. CONCLUSIONS: For pathogens that require prolonged incubation periods and are less sensitive to conventional culturing methods, metagenomic next-generation sequencing (mNGS) can be a powerful supplement to pathogen screening and plays a significant role in the auxiliary diagnosis of complex infectious diseases.

Rapid detection of FadA in Fusobacterium nucleatum using the quantitative LAMP colorimetric phenol red method in stool samples from colorectal cancer patients.

The study aimed to develop a quantitative colorimetric loop-mediated isothermal amplification technique using the phenol red indicator (QLAMP-PhR) for detecting Fusobacterium nucleatum (Fn) levels in colorectal cancer (CRC) patients and healthy individuals. QLAMP-PhR assays were conducted on 251 stool samples specific for the Fn FadA gene. Six primers were synthesized and utilized with master mix reagents, and a phenol red indicator was employed to enhance the QLAMP-PhR technique. A standard quantitative analysis curve was generated using a logarithmic function (absorbance vs. concentration) by serially diluting the copy number of genomic DNA templates (Fn ATCC25586). The CRC group exhibited a significantly higher abundance of Fn compared to the healthy control group (P < 0.001). These findings suggest that the QLAMP-PhR technique effectively identifies Fn specifically by its gene for the key virulence factor FadA. Additionally, ideas for developing a real-time QLAMP-PhR test were presented. Compared to the traditional polymerase chain reaction (PCR) technique, QLAMP-PhR offers several advantages including rapidity, simplicity, specificity, sensitivity, and cost-effectiveness method that can quantitatively screen for Fn presence in normal populations. The QLAMP-PhR method represents a sensitive and specific amplification assay for the rapid detection of the Fn pathogen. To the best of our knowledge, this study is the first to report the application of QLAMP-PhR for detecting FadA in Fn.

Symptoms predictive of Fusobacterium necrophorum pharyngotonsillitis - an observational study of cases presenting to hospitals in Southern Sweden.

OBJECTIVES: Fusobacterium necrophorum is a common cause of pharyngotonsillitis. However, no guidelines exist on when to diagnose or treat it. We aimed to investigate associations between clinical criteria and F. necrophorum-positivity in pharyngotonsillitis and assess the predictive potential of a simple scoring system. METHODS: Pharyngotonsillitis patients who were tested for F. necrophorum (PCR) and presented to hospitals in the Skåne Region, Sweden, between 2013-2020 were eligible. Data were retrieved from electronic chart reviews and registries. By logistic regression we investigated associations between F. necrophorum-positivity and pre-specified criteria: age 13-30 years, symptom duration ≤ 3 days, absence of viral symptoms (e.g. cough, coryza), fever, tonsillar swelling/exudate, lymphadenopathy and CRP ≥ 50 mg/L. In secondary analyses, associated variables were weighted by strength of association into a score and its predictive accuracy of F. necrophorum was assessed. RESULTS: Among 561 cases included, 184 (33%) had F. necrophorum, which was associated with the following criteria: age 13-30, symptom duration ≤ 3 days, absence of viral symptoms, tonsillar swelling/exudate and CRP ≥ 50 mg/L. Age 13-30 had the strongest association (OR5.7 95%CI 3.7-8.8). After weighting, these five variables had a sensitivity and specificity of 68% and 71% respectively to predict F. necrophorum-positivity at the proposed cut-off. CONCLUSION: Our results suggest that F. necrophorum cases presenting to hospitals might be better distinguished from other pharyngotonsillitis cases by a simple scoring system presented, with age 13-30 being the strongest predictor for F. necrophorum. Prospective studies, involving primary care settings, are needed to evaluate generalisability of findings beyond cases presenting to hospitals.

Lemierre syndrome with pulmonary empyema caused by Prevotella intermedia.

Lemierre syndrome is a rare disease that is most often caused by Fusobacterium necrophorum We present a case caused by Prevotella intermedia in a young, healthy man, complicated by multiple cavitary lung lesions, loculated pleural effusions requiring chest tube placement and trapezius abscess. Our case highlights (a) P. intermedia as a rare cause of Lemierre syndrome and (b) clinical response to appropriate antimicrobial therapy may be protracted.

Epidemiology and Clinical Outcomes of Fusobacterium Infections: A Six-Year Retrospective Study.

Background and Objectives: Anaerobic bacteria like Fusobacterium can lead to severe and life-threatening infections. The inherent complexities in the isolation of these bacteria may result in diagnostic and therapeutic delays, thereby escalating both morbidity and mortality rates. We aimed to examine data from patients with infections due to Fusobacterium to gain insights into the epidemiology and clinical outcomes of patients with these infections. Methods and Results: We conducted a retrospective analysis of clinical data from a cohort of patients with cultures positive for Fusobacterium species at a tertiary care medical center in the United States. Between 2009 and 2015, we identified 96 patients with cultures positive for Fusobacterium. Patients could be categorized into three groups based on the site of primary infection. Patients with head and neck infections constituted 37% (n 36). Patients with infections of other soft tissue sites accounted for 38.5% (n 37). Patients with anaerobic bacteremia due to Fusobacterium formed 24% (n 23) of the cohort. Surgical intervention coupled with antibiotic therapy emerged as cornerstones of management for patients with head and neck or other soft tissue infections, who generally exhibited more favorable outcomes. Patients with bacteremia were older, more likely to have malignancy, and had a high mortality rate. When speciation was available, Fusobacterium necrophorum was the most frequently isolated species. Conclusions: Our retrospective analysis of epidemiology and clinical outcomes of Fusobacterium infections revealed three distinct cohorts. Patients with head, neck, or soft tissue infections had better outcomes than those with bacteremia. Our findings highlight the importance of employing management strategies based on infection site and underlying comorbidities in patients with Fusobacterium infections. Further research is needed to investigate the optimal therapeutic strategies and identify prognostic indicators to improve clinical outcomes for these complex infections.

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

The first case report: diagnosis and management of necrotizing fusobacterium lung abscess via BALF next-generation sequencing.

BACKGROUND: Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can lead to diagnostic difficulties. METHODS: We report a case of F. necrophorum lung abscess diagnosed by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF). RESULTS: BALF-NGS detected F. necrophorum, guiding subsequent targeted antibiotic therapy. With active drainage and metronidazole treatment, the patient's condition was effectively treated. CONCLUSION: BALF-NGS is a valuable tool for the rapid diagnosis of infections caused by difficult-to-culture bacteria. It played a decisive role in the early identification of F. necrophorum, enabling timely and targeted antibiotic intervention. Early diagnosis and appropriate treatment are crucial for the management of F. necrophorum pneumonia.

Fusobacterium necrophorum intratonsillar abscess as a source of bacteremia in a patient with a history of substance abuse.

A 22-year-old male, with a history of recreational drug use, was admitted with a 24-hour history of sore throat, bilateral otalgia, fever, chills, sweats, and pain in the upper chest. The blood cultures were positive for Fusobacterium necrophorum. A thoracic and neck soft tissue computed tomography (CT) scan revealed an intratonsillar abscess and pulmonary septic emboli. Initial treatment with Piperacillin-tazobactam and Clindamycin was de-escalated after 5 days. The patient made a complete recovery after 22 days of antibiotic treatment.

Low usefulness of reporting tonsillar PCR Ct-values in pharyngeal infections with Fusobacterium necrophorum.

Tonsillar Fusobacterium necrophorum PCR Ct-values were higher in participants with asymptomatic tonsillar carriage than patients with pharyngeal infections. However, Ct-values were not associated with severity of disease or predictive of development of complications and hence lacked clinical usefulness. The reporting of F. necrophorum Ct-values in clinical samples is not recommended.

Peritonsillar abscess caused by Mycoplasma hominis and Fusobacterium necrophorum following oral sex.

Mycoplasma hominis is a bacterium that colonizes the genital tract of some females and males, as well as their respiratory tracts. Although only two cases of deep neck infection have been reported, the associations between the onset and sexual intercourse have not been reported. A healthy 19-year-old female was diagnosed with a left peritonsillar abscess. The patient had sexual intercourse with a new partner, including oral sex, two days prior to symptom onset. It was not known whether the male partner had urethritis symptoms. M. hominis and Fusobacterium necrophorum were isolated from the abscess culture. The patient's condition improved after drainage, and sulbactam ampicillin was switched to oral clindamycin.

Cryptogenic pyogenic liver abscess caused by Fusobacterium necrophorum in an immunocompetent patient.

Pyogenic liver abscesses are potentially fatal conditions that require prompt treatment with drainage and appropriate antimicrobial therapy. Fusobacterium necrophorum is a gram-negative rod that is found in the oral cavity, gastrointestinal tract and female genital tract. It is an extremely rare cause of liver abscess, particularly in the absence of risk factors or exposures. We describe an unusual case of a cryptogenic F. necrophorum hepatic abscess without a clear source despite extensive investigation in a young, immunocompetent patient without known risk factors or exposures for such an infection.

Fusobacterium Necrophorum bacteremia involving multi-organ systems.

A 62-year-old African American man with a history of avascular necrosis (AVN) of the right hip joint presented with severe right hip pain, dyspnea, fever, tachycardia, and hypertension. Computed tomography (CT) scan showed bilateral airspace opacities with a mild tree-in-bud nodularity in the left lower lobe. Ultrasonography of the lower extremities revealed a deep venous thrombus (DVT) in the right deep veins. Blood cultures grew Fusobacterium necrophorum. CT and magnetic resonance imaging showed right hip joint destruction and septic arthritis. The patient had a complicated hospital course leading to total hip arthroplasty with antibiotic-impregnated cementing.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Culture-Negative Fusobacterium nucleatum Brain Abscess and Pleural Empyema Cases Revealed by 16S rRNA Sequencing.

BACKGROUND: We reported two Fusobacterium nucleatum cases each of brain abscesses and pleural empyema, using 16S rRNA sequencing technology. METHODS: We reviewed clinical records and microbiological findings in four patients with F. nucleatum infection. RESULTS: All conventional culture results from peripheral blood, cerebrospinal fluid, and pleural fluid samples were found to be negative for this pathogen. Three patients were treated with antimicrobial agents for more than a week before specimen sampling. All patients recovered from their fusobacterial infections and were discharged. CONCLUSIONS: Molecular identification methods such as 16S rRNA sequencing should accompany conventional culture to detect obligate anaerobic bacteria in deep-seated sites and organs.

Complex Lemierre syndrome with multisystemic abscesses.

We present here the challenging case of severe Lemierre syndrome in a healthy woman in her late twenties, whose clinical presentation was characterised by lung abscesses and disseminated systemic abscesses in the brain, the abdomen and the soft-tissues, as a likely consequence of a patent foramen ovale. Blood cultures were positive for Fusobacterium necrophorum and a right lingual vein thrombosis was detected at a late stage when the patient developed a septic shock. Initial antimicrobial therapy with metronidazole and ceftriaxone was modified to meropenem due to progressive worsening. The patient underwent laparoscopy and neurosurgical drainage of a cerebral abscess. She spent many days in the intensive care unit and recovered fully after 6 weeks on meropenem therapy. Although considered rare, the incidence of Lemierre syndrome, a potentially life-threatening condition, is increasing. The clinician should promptly recognise and treat it while being aware of its potential atypical presentations.

Associations Between Findings of Fusobacterium necrophorum or ß-Hemolytic Streptococci and Complications in Pharyngotonsillitis-A Registry-Based Study in Southern Sweden.

BACKGROUND: Most pharyngotonsillitis guidelines focus on the identification of group A streptococci (GAS), guided by clinical scores determining whom to test with a rapid antigen detection test. Nevertheless, many patients testing negative with this test are evaluated for group C/G streptococci (GCS/GGS) and Fusobacterium necrophorum, yet their importance remains debated. Our primary aim was to evaluate associations between complications and findings of F. necrophorum, GAS, or GCS/GGS in pharyngotonsillitis. METHODS: This was a retrospective, registry-based study of pharyngotonsillitis cases tested for F. necrophorum (polymerase chain reaction) and ß-hemolytic streptococci (culture) in the Skåne Region, Sweden, in 2013-2020. Patients with prior complications or antibiotics (within 30 days) were excluded. Data were retrieved from registries and electronic charts. Logistic regression analyses were performed with a dichotomous composite outcome of complications as primary outcome, based on International Classification of Diseases, Tenth Revision, codes. Cases with negative results (polymerase chain reaction and culture) were set as reference category. Complications within 30 days were defined as peritonsillar or pharyngeal abscess, otitis, sinusitis, sepsis or septic complications, recurrence of pharyngotonsillitis (after 15-30 days) or hospitalization. RESULTS: Of 3700 registered cases, 28% had F. necrophorum, 13% had GCS/GGS, 10% had GAS, and 54% had negative results. The 30-day complication rates were high (20%). F. necrophorum (odds ratio, 1.8; 95% confidence interval, 1.5-2.1) and GAS (1.9; 1.5-2.5) were positively associated with complications, whereas GCS/GGS were negatively associated (0.7; 0.4-0.98). CONCLUSIONS: Our results indicate that F. necrophorum is a relevant pathogen in pharyngotonsillitis, whereas the relevance of testing for GCS/GGS is questioned. However, which patient to test and treat for F. necrophorum remains to be defined.

Atypical involvement of the thyro-linguo-facial vein in Lemierre syndrome.

Fusobacterium necrophorum is a Gram-negative anaerobic bacterium that can lead to severe infection in young patients even without immunodeficiency. Due to the length of time for isolation and speciation of this Gram-negative bacillus (typically 5-8 days), and its potential mortality, broad-spectrum antibiotic therapy should be started without delay. With a cervical thrombosis, even on an unusual site and with a standard condition such as tonsillitis, Lemierre syndrome should be considered. We report a case of Lemierre syndrome in a previously healthy young woman.

Myometritis with pelvic septic vein thrombophlebitis secondary to Fusobacterium necrophorum sepsis.

A young woman in her 20s presented with fever, abdominal pain and malodourous vaginal discharge. She was found to be in septic shock, in the setting of a recent medical abortion with subsequent intrauterine device placement. Her blood cultures grew Fusobacterium necrophorum Despite appropriate antibiotic therapy, the fever failed to defervesce. Subsequent evaluation revealed septic thrombophlebitis of the right gonadal vein and branches of the right iliac vein. She improved with a prolonged course of targeted antimicrobial therapy.

Atypical presentation of Lemierre syndrome in a young healthy man with acute jaundice.

This report presents a case of Lemierre syndrome caused by Fusobacterium necrophorum in a healthy young adult who presented atypically with shortness of breath and jaundice but no clinical or diagnostic evidence of thrombophlebitis. Due to this unusual presentation with jaundice, diagnosis was challenging and delayed. However, the patient was successfully initiated on a prolonged course of intravenous antibiotics; he required a period in the intensive care unit and was discharged without significant complications. This report aims to raise awareness of the diagnosis and treatment of this rare condition and to highlight both common and unusual presentations of the syndrome.