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.

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 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.

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.

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.

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.

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.

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.

A case report of severe Fusobacterium nucleatum sepsis secondary to nephrectomy.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a resident anaerobic bacterium, which in rare cases may invade blood from the head and neck or the digestive tract to cause bacteremia and induce venous thrombosis. F. nucleatum is closely related to abdominal tumors, but it has not been reported in relation to renal tumors. We report herein a possible case. CASE PRESENTATION: This patient had kidney cancer with thrombosis in the right renal vein but had no sign of infection. After radical nephrectomy, thrombi formed in his left renal vein, and when removed, severe sepsis occurred. He did not respond to treatment with antibiotics and died, but the blood culture done confirmed that he had F. nucleatum bacteremia. CONCLUSION: F. nucleatum may also be associated with kidney cancer, and could cause post-operative renal vein thrombosis, and sepsis or septic shock after thrombectomy.

Diagnosis, treatment and prognosis of otomastoiditis induced by Fusobacterium necrophorum: A retrospective multicentre cohort study.

OBJECTIVES: Otomastoiditis caused by the anaerobic Fusobacterium necrophorum (F. necrophorum) often induces severe complications, such as meningitis and sinus thrombosis. Early diagnosis is difficult, partly because little is known about specific early signs. Comprehensive research about clinically chosen antimicrobial therapy has not been done yet and prognostic information about otomastoiditis caused by F. necrophorum is scarce. More knowledge about this subject is required. METHODS: In this retrospective cohort study, we included all cases of otomastoiditis caused by F. necrophorum treated in two university medical centres in the Netherlands during the past 10 years. Data was gathered from patient records and analysed using independent sample T-tests and Chi2-tests. RESULTS: This study reveals that otomastoiditis caused by F. necrophorum potentially induces neurological sequelae. Thereby, 80% of all included patients (n = 16) needed readmission within six months due to recurrence or complications of otomastoiditis caused by F. necrophorum. Mean (range) of age, CRP and temperature were 4.5 years (0.9-29.3), 243 mg/L (113-423) and 40 °C (37-41). All patients were hospitalized and treated with antibiotics, mostly metronidazole (n = 13/16) and a ß -lactam (n = 15/16). Additional treatment contained low molecular weight heparin (83%, n = 10/12), dexamethasone (78%, n = 7/9) and/or surgery (80%, n = 12/16, whereof 9/12 mastoidectomy). CONCLUSIONS: Patients and/or their parents need to be informed about this potential unfortunate prognosis when otomastoiditis caused by F. necrophorum is diagnosed. To improve early diagnosis, otomastoiditis caused by F. necrophorum should be suspected and therefore immediately cultured when a) young children present with otomastoiditis, with b) high CRP values, and/or c) vomiting and decreased consciousness.

Short blood culture time-to-positivity in Fusobacterium necrophorum bacteremia is associated with Lemierre's syndrome.

The usefulness of blood culture time-to-positivity (TTP) in the diagnosis of endovascular infections has previously been shown. Here, we investigated TTP in 41 patients with F. necrophorum bacteraemia and found an association between short TTP and Lemierre's syndrome (p = 0.026).

Fusobacterium necrophorum oral infections - A need for guidance.

F. necrophorum, a gram-negative obligate anaerobe, causes pharyngotonsillitis, peritonsillar abscess and the Lemierre Syndrome as well as other significant infections. Clinical information on this bacterium has increased dramatically over the past 20 years, yet no standard guidance exists for treating these infections. While data support F. necrophorum as a cause of pharyngotonsillitis, no consensus exists on the clinical importance of these findings especially in the 15-30 age group. Similarly, recent data find this bacterium the most frequent and most likely to recur in peritonsillar abscess for that age group. Should this impact how we treat these patients? Finally, we have no studies of either antibiotics or anticoagulation for the Lemierre Syndrome. Thus, each physician making the diagnosis of the Lemierre Syndrome chooses antibiotics (and their duration) and whether or not to anticoagulate without guidance. Infectious disease specialists and hospitalists would benefit from consensus expert opinions based on reviewing data on these infections.

Postpartum Fusobacterium gonidiaformans bacteremia.

We present a case of a healthy 29 year-old female with an uneventful vaginal delivery who had transient, sudden onset of rigors and fever 36 hours postpartum. She was found to have Fusobacterium gonidiaformans bacteremia due to retained placental tissue. We report this organism as it is not well-described and rarely reported. It does bear some similarities to other Fusobacterium species that have been reported to cause septicemia in young otherwise healthy patients.

An immunocompetent patient with culture-negative multiple brain abscesses caused by Fusobacterium nucleatum.

The diagnosis and treatment of brain abscesses have advanced due to the utilization of modern microbiological and neurosurgical methods. Here we present a 49-year-old female patient presented with headache and neurological symptoms. Initial evaluation revealed multiple ring-enhanced brain lesions and a lung cavitary lesion initially suspected to represent a malignant process. Stereotactic aspiration provided the diagnosis of brain abscesses but yielded negative cultures. 16S ribosomal RNA analysis enabled the identification of Fusobacterium nucleatum. For ten weeks, the patient was treated with ceftriaxone and metronidazole. A marked clinical and radiological improvement was noted. Brain abscess is a severe intracranial infectious process with significant morbidity and mortality. Microbiological analysis is challenging due to the location of the infection, the broad spectrum of causative agents, and the low yield of cultures. Fusobacterium nucleatum is an anaerobic bacteria with a tendency to abscess formation and is isolated from 2% of brain abscesses. The utilization of 16S RNA analysis improves microbiological identification rates in brain abscesses, as in other infectious entities, enabling better pathogen characterization and more suitable treatment.

Fusobacterial brain abscess caused by paradoxical embolization associated with Ebstein's anomaly in an adult patient: A case report.

Brain abscess remains a life-threatening condition. Here, we are reporting a case of brain abscess due to Fusobacterium nucleatum in a previously known case of Ebstein anomaly. A 44-year-old male presented with the complaints of headache, and fever. Cerebral imaging revealed parieto-occipital (PO) abscess. The abscess was drained and culture showed growth of Fusobacterium nucleatum. This report illustrates the importance of considering anaerobes as the cause of brain abscess, underscores the usefulness of MALDI, which facilitated the selection of appropriate and prompt adjuvant antibiotic therapy and a favourable outcome.

Fusobacterium nucleatum bacteremia with pneumopathy in a patient receiving eculizumab: A case report.

Fusobacterium nucleatum is a common oral commensal bacterium capable of severe invasive infections. We report a case of a diffuse bilateral pneumopathy with F. nucleatum-positive blood culture successfully treated by common antibiotics in a patient receiving eculizumab for a drug-induced thrombotic microangiopathy (TMA). It is the first described case of a severe F. nucleatum-associated infection in a patient undergoing terminal complement inhibitor therapy. We suggest providing preventive dental care before eculizumab initiation.

Atypical presentation of Lemierre's syndrome: case report and literature review.

BACKGROUND: The classic Lemierre's syndrome refers to a septic thrombosis of the internal jugular vein, usually caused by a Fusobacterium necrophorum infection starting in the oral cavity, and typically complicated by pulmonary emboli. However, unusual forms of the disorder have been rarely reported. CASE PRESENTATION: We describe an unusual case of a previously healthy 58-year-old male with Lemierre's syndrome, manifesting with lumbar pain and fever. A thrombosis of the iliac veins and abscesses in the right iliac and the left psoas muscles was diagnosed by a computed tomography scan, together with a right lung pneumonia complicated by pleural effusion and an L4-L5 spondylodiscitis. Blood culture and pus drainage were positive for Fusobacterium nucleatum and an atypical Lemierre's syndrome was suspected. The patient was treated with anticoagulant therapy for 12 weeks and intravenous antibiotic therapy for 6 weeks with a good evolution and resolution of the thrombosis. CONCLUSIONS: This case illustrates the thrombogenic and thromboembolic tendency of Fusobacterium nucleatum and its potential invasiveness, regardless of the site of primary infection. The concept of an atypical Lemierre's syndrome is redefined here to take into consideration non-cervical sites.

Lemierre's syndrome: One rare disease-Two case studies.

WHAT IS KNOWN AND OBJECTIVE: Lemierre's syndrome is often misdiagnosed as a common cold or viral infection. Fusobacterium necrophorum is the most common causative organism. The recommended treatment regimen is 6 weeks of a beta-lactam antibiotic along with metronidazole. CASE DESCRIPTION: We present two cases of Lemierre's syndrome with internal jugular vein thrombophlebitis and positive blood cultures for F. necrophorum. The first case was successfully treated with 6 weeks of a beta-lactam antibiotic and 4 weeks of metronidazole, while the second case was successfully treated with 4 weeks of a beta-lactam antibiotic and 2 weeks of metronidazole. WHAT IS NEW AND CONCLUSION: Two cases of Lemierre's syndrome were treated successfully with only 2-4 weeks of metronidazole therapy. Shorter duration of metronidazole therapy should be explored in future studies.

Rare isolation of Fusobacterium varium from a case of Fournier's gangrene.

Fusobacterium is a gram negative obligate anaerobic bacilli, a normal inhabitant of gastrointestinal tract, oropharynx and female genital tract. Here we report a case of Fourniers gangrene from which Fusobacterium varium has been isolated along with certain other pathogens. There are only a few reported cases of Fusobacterium varium in literature and it has never been reported from Fournier's gangrene. Through this report we intend to shed some light on the pathogenic potential of anaerobes which are considered as normal flora.