Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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.

OBJECTIVE: We aimed to explore the impact of social distancing on the incidence and microbiology of peritonsillar abscess (PTA).
METHODS: We performed a cross-sectional analysis of all patients with PTA and their microbiological findings in the 2 years preceding versus the 2 years following the COVID-19 lockdown in Denmark (11 March 2020), who were admitted to the Ear-Nose-Throat Department, Aarhus University Hospital. Age-stratified population data for the catchment area were obtained from Statistics Denmark.
RESULTS: The annual incidence rate was significantly higher in the 2-year period before (21.8 cases/100 000 inhabitants) compared with after (14.9 cases/100 000) the lockdown (p < 0.001). The number of cases with growth of Streptococcus pyogenes was significantly higher in the period before (n = 67) compared with after (n = 28) the lockdown (p < 0.001), whereas the number of cases positive for Fusobacterium necrophorum (n = 60 vs. n = 64) and streptococcus anginosus group (SAG) (n = 37 vs. n = 43) were stabile (p 0.79 and p 0.58, respectively). The relative prevalence of S. pyogenes was significantly higher in the period before (67/246 cultures, 27%) compared with after (28/179, 16%) the lockdown (p 0.007). On the contrary, the relative prevalence of F. necrophorum and SAG is significantly lower before (60/246, 24% and 37/246, 15%) compared with after (64/179, 36% and 43/179, 24%) the lockdown (p 0.013 and p 0.023).
CONCLUSIONS: Social distancing had a significant impact on the incidence and microbiology of PTA. Our findings suggest that S. pyogenes-positive PTA is highly related to direct social interaction, and represents a contagious pathogen. By contrast, PTA development caused by F. necrophorum and SAG is unrelated to direct social interaction and may be derived from flora imbalance.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.

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.
This was a retrospective, registry-based study of pharyngotonsillitis cases tested for F. necrophorum (polymerase chain reaction) and β-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.
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).
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 necrophorum causes a range of mild to life threatening infections and there is uncertainty in terms of diagnosis and treatment due to the lack of knowledge on their pathogenic mechanisms. This study characterised genomes of F. necrophorum to compare their virulence factors and investigate potential infection markers. 27 isolates of F. necrophorum from patients with pharyngotonsillitis were subjected to whole genome sequencing and compared with 42 genomes published in the NCBI database. Phylogenomics, pangemome, pan-GWAS and virulome were analysed to study strain variations with reference to virulence factors. Core genome based phylogenomic tree exhibited three clades of which Clade A belonged to F. necrophorum subsp necrophorum, clades B and C were F. necrophorum subsp funduliforme. Pan-GWAS and Pan-Virulome suggest some marker genes associated with clinical sources of isolation that needs further validation. Our study highlights some interesting features of the pathogenesis of F. necrophorum infections. Although the animal isolate genomes had some marker genes, the genomes of human isolates did not exhibit clear correlation to their clinical sources of isolation. This prompts to think of other mechanisms such as co-infections or host factors that can be involved in the pathogenesis.

OBJECTIVE: 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 β -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.

The past decade has witnessed a rise in Fusobacterium infections. This study aimed to describe the epidemiology, clinical and demographic characteristics and outcomes associated with Fusobacterium infections in hospitalized children in central Israel.
We retrospectively analyzed the medical records of children <18 years old who had been admitted with a diagnosis of invasive Fusobacterium infection (IFI) between January 2010 and April 2020. Clinical, laboratory and microbiologic data were retrieved. IFI diagnosis was based upon microbiological identification in any specimen by culture or by 16S ribosomal RNA polymerase chain reaction.
Fifty-one children (26 boys) with a median age of 3 years (range, 5-16 years) were included. Hospitalizations for IFI increased from 19 of 100,000 admissions between 2010 and 2015 to 50 of 100,000 between 2016 and 2020, representing a 2.5-fold increase. Most of the infections were from an otogenic source (n = 28, 55%) followed by an oropharyngeal/respiratory source (n = 21, 41%). The most common complications were subperiosteal and epidural abscesses (41% and 37%, respectively). Thrombosis was diagnosed in 11 children, 10 of whom had sinus vein thrombosis. All had an otogenic source. Children with otogenic compared with all other infection sources were significantly younger (median age of 1.9 vs. 3 years; P < 0.001). Forty-seven children (92%) underwent a surgical intervention. All patients survived, one with neurologic sequelae.
The admissions for IFI in children increased 2.5-fold during the last decade. The most common source is otogenic, especially among younger children, and it is associated with high complication rates. Current management, including combinations of antibiotics and surgical interventions, leads to favorable outcome.

While Fusobacterium necrophorum historically has been considered normal tonsillar flora, recent studies from Europe and the US have suggested that carriage occur transiently in adolescence and young adulthood. However, no studies originating from Africa exist. In this cross-sectional study of tonsillar carriage of F. necrophorum, we aimed to investigate geographical differences in tonsillar carriage rates of F. necrophorum in healthy participants aged 15-25 years in Sweden and Zambia and further investigate the age distribution of tonsillar carriage in Zambia. Specimens were obtained by tonsillar swabs and analyzed with real-time PCR for F. necrophorum. In participants aged 15-25 years, tonsillar carriage was more common in Sweden 21/100 (21%) than in Zambia 6/192 (3%), p < 0.001. In Zambian participants aged above 25 years tonsillar carriage was rare 1/76 (1%). In conclusion, the high rate of tonsillar carriage in participants aged 15-25 years in Sweden has implications on the interpretation of tonsillar findings in patients with pharyngotonsillitis. Interestingly, a geographical difference was found with tonsillar carriage rarely identified in Zambia.