Intra-spinal abscess due to Bacteroides fragilis and Klebsiella pneumoniae co-infection in a child with spinal dysraphism.

Bacteroides fragilis (B. fragilis) is an uncommon cause of spinal abscess. We present a case of an 18-month-old child, with spinal dysraphism-Spina bifida occulta, who developed intra-spinal abscess infection with B. fragilis and Klebsiella pneumoniae. Magnetic resonance imaging (MRI) of the brain and spine showed multiple abscesses extending through the presacral fistula into the spinal cord. Patient was surgically treated along with administration of antimicrobial agents (ceftriaxone and metronidazole), resulting in an excellent clinical outcome.

Bacteroides fragilis vertebral osteomyelitis: A rare clinical entity.

Acute pyogenic vertebral osteomyelitis is mainly attributed to haematogenous spread of aerobic bacteria, while anaerobic osteomyelitis results from contiguous spread of polymicrobial infections through breaks in the gut mucosal barrier and involves the vertebral bodies in only about 2%-5%. Herein, we report two cases of vertebral osteomyelitis due to Bacteroides fragilis. It is noteworthy that cases of vertebral osteomyelitis due to Bacteroides fragilis have been attributed to the extension of intra-abdominal or pelvic floor infections. However, in the two cases described, there was no history of a previous medical intervention nor an intestinal or pelvic floor infection. Early recognition of the aetiological agent that causes vertebral osteomyelitis may lead to the timely treatment and therefore, may deter any neurosurgical/orthopaedic interventions.

A systemic review of the role of enterotoxic Bacteroides fragilis in colorectal cancer.

Enterotoxigenic Bacteroides fragilis (ETBF) has received significant attention for a possible association with, or causal role in, colorectal cancer (CRC). The goal of this review was to assess the status of the published evidence supporting (i) the association between ETBF and CRC and (ii) the causal role of ETBF in CRC. PubMed and Scopus searches were performed in August 2021 to identify human, animal, and cell studies pertaining to the role of ETBF in CRC. Inclusion criteria included the use of cell lines, mice, exposure to BFT or ETBF, and detection of bft. Review studies were excluded, and studies were limited to the English language. Quality of study design and risk of bias analysis was performed on the cell, animal, and human studies using ToxRTools, SYRCLE, and NOS, respectively. Ninety-five eligible studies were identified, this included 22 human studies, 24 animal studies, 43 cell studies, and 6 studies that included both cells and mice studies. We found that a large majority of studies supported an association or causal role of ETBF in CRC, as well as high levels of study bias was detected in the in vitro and in vivo studies. The high-level heterogeneity in study design and reporting made it difficult to synthesize these findings into a unified conclusion, suggesting that the need for future studies that include improved mechanistic models, longitudinal in vitro and in vivo evidence, and appropriate control of confounding factors will be required to confirm whether ETBF has a direct role in CRC etiopathogenesis.

Risk Factors for Enterotoxigenic Bacteroides fragilis Infection and Association with Environmental Enteric Dysfunction and Linear Growth in Children: Results from the MAL-ED Study.

Despite reports of enterotoxigenic Bacteroides fragilis (ETBF) isolation from asymptomatic children, no reports exist regarding the possible association of ETBF with long-term complications such as development of environmental enteric dysfunction (EED) and subsequent linear growth faltering in childhood. We aimed to establish a potential association between the burden of asymptomatic ETBF infection and EED and linear growth at 24 months of age using the data collected from 1,715 children enrolled in the multi-country birth cohort study, known as the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health study. Using Poisson regression models, we evaluated the site-specific incidence rate and, subsequently, identified the risk factors and assessed the association between the burden of ETBF infection and EED score and linear growth at 24 months of age. The overall incidence rate of ETBF infections per 100 child-months across all study sites was 10.6%, with the highest and lowest incidence of ETBF infections being reported in Tanzania (19.6%) and Peru (3.6%), respectively. Female gender, longer duration of breastfeeding, and improved water access, sanitation, and hygiene practices, such as improved drinking water source, improved sanitation, and improved floor material in households, along with enhanced maternal education and less crowding in the households were found to be protective against incidences of ETBF infection. The burden of ETBF infections was found to have significant associations with EED and linear growth faltering at 24 months of age across all the study sites. Our findings warrant regular clinical monitoring to reduce the burden of ETBF infections and diminish the burden of enteropathy and linear growth faltering in childhood.

Fusobacterium nucleatum and Bacteroides fragilis detection in colorectal tumours: Optimal target site and correlation with total bacterial load.

BACKGROUND: Mucosal infiltration by certain bacterial species may contribute to the development and progression of colorectal cancer (CRC). There is considerable variation in reported detection rates in human CRC samples and the extent to which bacterial infiltration varies across regions of the primary tumour is unknown. This study aimed to determine if there is an optimal site for bacterial detection within CRC tumours. METHODS: Presence of target bacterial species was assessed by quantitative real-time PCR (qPCR) in 42 human CRC tumours. Abundance in primary tumour regions, normal epithelium and at metastatic sites was investigated in an expanded cohort of 51 patients. Species presence/absence was confirmed by diversity profiling in five patients. Correlation with total bacterial load and clinicopathological features was assessed. RESULTS: Fusobacterium nucleatum and Bacteroides fragilis were detected in tumours from 43% and 24% of patients, respectively (17% positive for both species). The optimal detection site was the tumour luminal surface (TLS). Patients testing positive at the TLS frequently tested negative at other sites, including central tumour and invasive margin. F. nucleatum was detected at a higher frequency in tumour versus normal epithelium (p < 0.01) and was associated with more advanced disease (p = 0.01). Detection of both species correlated with total bacterial load. However, corroboration of qPCR results via diversity profiling suggests detection of these species may indicate a specific microbial signature. CONCLUSIONS: This study supports a role for F. nucleatum in CRC development. Presence of F. nucleatum and B. fragilis varies across primary tumour regions, with the TLS representing the optimal site for bacterial detection.

A preliminary study on the role of Bacteroides fragilis in stent encrustation.

OBJECTIVE: To preliminarily study the characteristics of bacterial flora distribution in the urine of ureteral stent encrustation patients as well as the relation between Bacteroides and stent encrustation. METHODS: Patients undergoing ureteral stenting were included in the study and divided into encrustation group and non-encrustation group based on the condition of stent encrustation. The urine of patients was collected to undergo 16s DNA test to compare the bacterial flora distribution characteristics of the two groups. The bacterial genus with highest abundance in the urine of encrustation group was used for animal experiment. A rat model with a foreign body in the bladder was created, in which the rats were injected with the aforesaid bacterial genus. A control group injected with normal saline was also formed. The incidence of foreign body tube encrustation between the two groups was compared. RESULTS: The urine collected from the patients in encrustation group contained a variety of bacteria, while dominant bacteria genera included g_Lactobacillus (23.1%), g_Bacteroides (18.8%) and g_norank_Bacteroides (17.1%). While the urine from the non-encrustation group was less diverse in bacteria flora, as the major bacteria genera were g_Escherichia-Shigella (32.2%), g_Enterococcus (24.9%) and g_Pseudomonas (18.2%). Bacteroidetes in the encrustation group were significantly higher, therefore Bacteroides fragilis in this genus was adopted for animal experiment, resulting in a higher incidence of foreign body tube encrustation in the bladder among rats. CONCLUSION: The present study enriches our knowledge about ureteral stent encrustation and reveals that the target regulation of urine bacteria is worth further research and clinical application.

Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation.

Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic Bacteroides fragilis (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the Bacteroides fragilis toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.

First case of COVID-19 complicated with fulminant myocarditis: a case report and insights.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Enterotoxigenic Bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model.

The azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model is commonly used to study colitis-associated cancer. The human commensal bacterium, enterotoxigenic Bacteroides fragilis (ETBF) secretes the Bacteroides fragilis toxin (BFT) which is necessary and sufficient to cause colitis. We report that BALB/c mice infected with WT-ETBF and administered three cycles of AOM/DSS developed numerous, large-sized polyps predominantly in the colorectal region. In addition, AOM/DSS-treated BALB/c mice orally inoculated with wild-type nontoxigenic Bacteroides fragilis (WT-NTBF) overexpressing bft (rETBF) developed numerous polyps whereas mice infected with WT-NTBF overexpressing a biologically inactive bft (rNTBF) did not promote polyp formation. Unexpectedly, the combination of AOM+ETBF did not induce polyp formation whereas ETBF+DSS did induce polyp development in a subset of BALB/c mice. In conclusion, WT-ETBF promoted polyp development in AOM/DSS murine model with increased colitis in BALB/c mice. The model described herein provides an experimental platform for understanding ETBF-induced colonic tumorigenesis and studying colorectal cancer in wild-type mice.

Enterotoxigenic Bacteroides fragilis: A Possible Etiological Candidate for Bacterially-Induced Colorectal Precancerous and Cancerous Lesions.

Enterotoxigenic Bacteroides fragilis (ETBF) produces Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC). In experimental models, ETBF has been shown to contribute to colon carcinogenesis. The present study was conducted to investigate mucosal colonization of ETBF in the colon to find a possible association between the presence of ETBF and precancerous and cancerous lesions. The mucosal biopsies of involved sites were obtained from 68 patients with precancerous and cancerous lesions and 52 healthy controls (HC). The samples were cultured on Bacteroides Bile Esculin agar. Then, specific primers were designed to detect B. fragilis and bft gene using quantitative real-time PCR, and the possible links of ETBF with clinicopathological characteristics was evaluated. Also real-time PCR was performed to detect the bft gene subtypes. Bacteroides fragilis was detected in 51% of the patients and 48% of HCs cultures. The 16SrRNA gene was found to be present in 63 and 81% of the patients and HCs' samples, respectively. Moreover, the bft gene was detected in 47 and 3.8% of the patients and HCs, respectively. Also, B. fragilis was significantly more abundant in the patients' samples compared to those of HCs. In the patient group, higher odds ratio (OR) of ETBF was significantly associated with serrated lesions and adenoma with low-grade dysplasia. The bft1 gene was the most prevalent subtype of bft gene, followed by the bft2 gene. This was the first study in Iran to demonstrate increased positivity of ETBF in patients with precancerous and cancerous lesions. In this study, the bft gene was found to be associated with CRC, especially in the patients with precancerous lesions and initial carcinogenic lesions. Moreover, the results suggest that mucosal BFT exposure is common and could be a risk factor and a screening marker for developing CRC.

Fecal peritonitis in aging rat model. Therapeutic response to different antibiotic strategies.

PURPOSE: To evaluate the response of aging rats with sepsis to two different antibiotic regimens. METHODS: The study was conducted with 30 aging rats (18 month-old) with autologous feces peritonitis. The animals were divided into three groups: Group 0 received no therapeutic intervention (control), while Group 1 received a single dose of 40 mg/kg meropenem and Group 2 received a single dose of 20 mg/kg moxifloxacin. The intervention in both Groups was made 6 hours after induction of peritonitis. The animals were followed up to 15 days for evaluating morbidity and mortality. The weights at baseline were similar in all groups. RESULTS: At the end of follow-up, weight loss was significantly greater (p=0.0045) in Group 0 (non-intervention controls). Culture from a blood sample at the end of follow-up was positive in all the animals in Group 0, in two animals in Group 1 and in four animals in Group 2. Morbidity/mortality was significantly higher in Group 0 compared to both Groups 1 and 2 (p=0.003) but the scores were not significantly different between Groups 1 and 2 (p=0.6967). CONCLUSION: Both antibiotic regimens rendered promising results for the treatment of fecal peritonitis.

Fecal peritonitis in aging rat model. Therapeutic response to different antibiotic strategies

Abstract Purpose: To evaluate the response of aging rats with sepsis to two different antibiotic regimens. Methods: The study was conducted with 30 aging rats (18 month-old) with autologous feces peritonitis. The animals were divided into three groups: Group 0 received no therapeutic intervention (control), while Group 1 received a single dose of 40 mg/kg meropenem and Group 2 received a single dose of 20 mg/kg moxifloxacin. The intervention in both Groups was made 6 hours after induction of peritonitis. The animals were followed up to 15 days for evaluating morbidity and mortality. The weights at baseline were similar in all groups. Results: At the end of follow-up, weight loss was significantly greater (p=0.0045) in Group 0 (non-intervention controls). Culture from a blood sample at the end of follow-up was positive in all the animals in Group 0, in two animals in Group 1 and in four animals in Group 2. Morbidity/mortality was significantly higher in Group 0 compared to both Groups 1 and 2 (p=0.003) but the scores were not significantly different between Groups 1 and 2 (p=0.6967). Conclusion: Both antibiotic regimens rendered promising results for the treatment of fecal peritonitis.

Sepsis Secondary to Bacteroides Fragilis Tubo-Ovarian Abscess Requiring Hysterectomy and Bilateral Salpingo-Oophorectomy.

A 45-year-old, G0P0 premenopausal woman was admitted for investigation of right lower quadrant pain, fever, leucocytosis and right adnexal abscess on CT. She was started on intravenous antibiotics and underwent CT-guided percutaneous drainage from which Bacteroides fragilis was cultured. A few days later, she had an exploratory laparotomy with incision and drainage. Once stabilised, she was discharged on intravenous antibiotics. She was followed outpatient and subsequent imaging demonstrated significant improvement of the abscess. After being asymptomatic for 3 months, she again presented to the emergency department with right lower quadrant abdominal pain, fever and leucocytosis. Two days later, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. She made a full recovery and began treatment with a herbal oestrogen derivative to prevent early menopause.

Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia.

BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum. METHODS: Mucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed. FINDINGS: We found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from the right side of the colon. CONCLUSION: Our results showing association of ETBF positivity and increased abundance with early-stage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis.

Clinical characteristics associated with mortality of patients with anaerobic bacteremia.

The presence of anaerobes in the blood stream is known to be associated with a higher rate of mortality. However, few prognostic risk factor analyses examining whether a patient's background characteristics are associated with the prognosis have been reported. We performed a retrospective case-controlled study to assess the prognostic factors associated with death from anaerobic bacteremia. Seventy-four patients with anaerobic bacteremia were treated between January 2005 and December 2014 at Aichi Medical University Hospital. The clinical information included drug susceptibility was used for analysis of prognostic factors for 30-day mortality. Multivariate logistic analyses revealed an association between the 30-day mortality rate and malignancy (OR: 3.64, 95% CI: 1.08-12.31) and clindamycin resistance (OR: 7.93, 95% CI: 2.33-27.94). The result of Kaplan-Meier analysis of mortality showed that the 30-day survival rate was 83% in clindamycin susceptible and 38.1% in clindamycin resistant anaerobes causing bacteremia. The result of log-rank test also showed that susceptibility to clindamycin affected mortality (P < 0.001). Our results indicated that malignancy and clindamycin susceptibility could be used to identify subgroups of patients with anaerobic bacteremia with a higher risk of 30-day mortality. The results of this study are important for the early and appropriate management of patients with anaerobic bacteremia.