Superior mesenteric veinous thrombosis with Bacteroides fragilis infection: a case report / 中国热带医学

@#Abstract: Superior mesenteric veinous thrombosis (SMVT) is a rare complication that often occurs in conjunction with intra-abdominal diseases such as diverticulitis, appendicitis, inflammatory bowel disease, etc. Its clinical symptoms are non-specific and include fevers, abdominal pain; it has no specific symptoms, and the diagnosis depends on clinical laboratory tests and imaging studies. The occurrence of superior mesenteric veinous thrombophlebitis is related to septic phlebitis caused by the sloughing of the embolus containing bacteria into the portal vein with blood flow. Due to the nonspecific clinical features of this disease, diagnosing it based on clinical characteristics and microbiological aspects is a challenge. A case of superior mesenteric veinous septic thrombophlebitis caused by Bacteroides fragilis infection is reported and to provide a reference for the diagnosis and treatment of such diseases. The patient was a 34-year-old man who was admitted the hospital with intermittent abdominal pain and fever. Computed tomography (CT) showed partial thrombosis of the superior mesenteric vein, colonoscopy revealed diverticulitis in the ileoceca, and the blood culture grew Bacteroides fragilis. The patient was treated with anti-infection (ceftazidime 2.0 g q12h intravenous infusion for 11 days; metronidazole 0.5 g, q8h intravenous infusion for 3 days) and anticoagulation (rivaroxaban 20 mg qd orally for 8 days. On the 11th day of hospitalization, the patient's condition improved, and he was discharged. In this case, for patients with fever and abdominal pain, superior mesenteric venous thrombophlebitis should be included in the differential diagnosis. Through auxiliary examination, blood sample culture and other technologies, clear diagnosis should be made in time to improve patient outcomes.

Mechanism of Polysaccharides from Two Spleen-invigorating Chinese Medicine Prescriptions in Regulating Growth of Bacteroides fragilis in vitro： Based on Differential Expression of Polysaccharide Utilization Loci / 中国实验方剂学杂志

ObjectiveTo investigate the effects of using the polysaccharides from two Chinese medicine compound prescriptions as the carbon source on the growth of Bacteroides fragilis and to decipher the mechanism from the perspective of differential expression of polysaccharide utilization loci （PULs） based on transcriptomics. MethodThe media with different carbon sources ［20% polysaccharides of Lizhongtang， polysaccharides of Shenling Baizhusan， glucose， and brain heart infusion （BHI） Broth］ were used for the anaerobic culture of B. fragile ATCC25285. The effects of different carbon sources on the growth of B. fragilis ATCC25285 were determined by continuous sampling and spectrophotometry. Then， transcriptome sequencing was performed for the cultures obtained with different carbon sources to study the mechanism of different carbon sources in regulating bacterial growth. ResultThe concentration of bacteria with the polysaccharide of Lizhongtang， polysaccharide of Shenling Baizhusan， BHI Broth， and glucose as the carbon sources peaked at 26， 32， 26， 38 h， respectively， and the bacteria in all the four groups achieved robust growth. Gene ontology （GO） enrichment indicated that the differentially expressed genes in the Lizhongtang polysaccharide group and Shenling Baizhusan polysaccharide group were concentrated in the transport and transmembrane transport of dicarboxylic acid. The Shenling Baizhusan polysaccharide and BHI Broth groups showed high expression of PUL 4 and 27， glycoside hydrolase 13 （GH13）， and glycosyl transferases 5 （GT5）. PUL9 was highly expressed in Shenling Baizhusan polysaccharide group， and PUL 17， 19， and 20， GH3， and GH144 in the BHI Broth group. PUL27 and GT5 were highly expressed in Shenling Baizhusan polysaccharide and glucose groups. PUL 4 and 9 and GH13 were only highly expressed in Shenling Baizhusan polysaccharide group， and PUL 2， 17， and 19 and GH2 in the glucose group. Both Lizhongtang polysaccharide group and BHI group highly expressed PUL 4， 17， 19， 20， and 27， GH3， and GH144. PUL 2， 8， 23， and 27， GH2， and GH57 were highly expressed in Lizhongtang polysaccharide group， while GH13 showed high expression in the BHI group. Both the glucose and Lizhongtang polysacharride groups showed high expression of PUL 4 and 27 and GH2. PUL 4， 8， 20， and 23， GH3， and GH144 were highly expressed in Lizhongtang polysaccharide group， while PUL30 was highly expressed in the glucose group. ConclusionThe in vitro experiments and transcriptome sequencing results confirmed that the expression of PULs and GH may provide benefits or costs to the adaptive growth of Bacteroides fragilis ATCC25285 cultured with different carbon sources， which may be one of the mechanisms by which polysaccharides from Chinese medicine compound prescriptions regulate the growth of B. fragilis ATCC25285. The findings can provide a reference for further research on the relationship between B. fragilis metabolic pathway and polysaccharides of Chinese medicine compound prescriptions.

Endophthalmitis caused by Bacteroides fragilis after pars plana vitrectomy and treatment approach

Rationale: Endophthalmitis is an uncommon but serious ocular infection often resulting in probable visual loss. Bacteroides fragilis is a rare cause of endophthalmitis. Patient concerns: A 46-year-old male patient complained of eye pain and low vision after pars plana vitrectomy. Diagnosis: Bacteroides fragilis endophthalmitis after pars plana vitrectomy was diagnosed. Interventions: Pars plana vitrectomy and silicone oil implantation were performed. Outcomes: Early treatment and choice of tamponade in endophthalmitis after pars plana vitrectomy may possibly prevent evisceration and progression of endophthalmitis. Lessons: Bacteroides fragilis can be seen in cases of endophthalmitis after pars plana vitrectomy.

Treatment of psoriasis vulgaris using Bacteroides fragilis BF839: a single-arm, open preliminary clinical study / 生物工程学报

Psoriasis is considered as an inflammatory disease driven by T cells, and its pathogenesis is closely related to the imbalance of intestinal bacteria flora. It has been reported that Bacteroides fragilis could play an anti-inflammatory role by regulating the expression of cytokines in T cells. To date, there is no report using B. fragilis to treat psoriasis. In this study, we explored the therapeutic effect of B. fragilis BF839 on psoriasis. We selected 27 psoriasis patients who were treated in the Second Affiliated Hospital of Guangzhou Medical University from April to October 2019. The patients were given B. fragilis BF839 orally for 12 weeks while maintaining the original treatment. The psoriasis area and severity index (PASI) score was evaluated before and after the treatment. The rate of drug withdrawal and reduction after 12 weeks of treatment were calculated. Our results showed that the rate of 12-week trial completion was 96.3% (26/27). We used PASIN to define the proportion of people whose PASI score decreased more than or equal to N% after treatment. At 12 weeks, PASI30, PASI50, and PASI75 were 65.4%, 42.3%, and 19.2%, respectively. The PASI score was 9.1±5.9 and 5.8±4.9 before and after 12 weeks of treatment respectively, and the difference was statistically significant (P0.05). The adverse reaction rate of patients was 3.8% (1/26) within 12 weeks of treatment, including 1 case of constipation, and the rate of drug withdrawal and reduction was 60.0%. The above results suggest that B. fragilis BF839 may be functional on the treatment of psoriasis by reducing the PASI score and the drug usage rate with few side effect, which deserves further study.

Recuperación de bacterias aerobias y anaerobias de pacientes con apendicitis aguda mediante botellas de hemocultivo / Recovery of aerobic and anaerobic bacteria from patients with acute appendicitis using blood culture bottles

Introducción. La apendicitis aguda es la primera causa de abdomen agudo; sin embargo, poco se conoce sobre las bacterias asociadas y su perfil de sensibilidad. Objetivo. Identificar y determinar el patrón de resistencia de las bacterias aerobias y anaerobias aisladas en cultivo de líquido periapendicular tomado de los pacientes con apendicitis aguda, y establecer la proporción de bacterias según la fase clínica. Materiales y métodos. Se llevó a cabo un estudio descriptivo y prospectivo en el Hospital Universitario de San José de Bogotá (Colombia), en pacientes mayores de 16 años sometidos a apendicectomía abierta. Se tomaron muestras de líquido periapendicular, las cuales se sembraron directamente en botellas de hemocultivos para aerobios y anaerobios. Resultados. Se incluyeron 154 pacientes. Del total de cultivos, el 87 % (n=134) fueron positivos: 77 % (n=118) para aerobios y 51 % (n=79) para anaerobios. La proporción de cultivos positivos fue inferior en los casos de apendicitis no complicada, en comparación con aquellos de apendicitis complicada (80 % (66/83) Vs. 95 % (67/71); p=0,003). Los microorganismos aislados con mayor frecuencia fueron: Escherichia coli (53 %) (n=84), Bacteroides sp. (25 %) (n=25), Propionibacterium acnes (21 %) (n=21), Staphylococci coagulasa negativo (17 %) (n=27), Enterococcus sp. (10 %) (n=15) y Fusobacterium sp. (11 %) (n=11). La sensibilidad de E. coli a la amplicilina sulbactam fue de 30 %. La sensibilidad de Bacteroides spp. a la clindamicina y la ampicilina sulbactam fue de 91 %. El 100 % de los anaerobios fueron sensibles a piperacilina tazobactam, ertapenem, meropenem y metronidazol. Conclusiones. Los cultivos intraoperatorios son pertinentes en la apendicitis para determinar el patrón epidemiológico local, y establecer los antibióticos profilácticos y terapéuticos para esta enfermedad. Su siembra directa en botellas de hemocultivo permite una gran recuperación de microorganismos.

Introduction: Acute appendicitis is the first cause of acute abdomen, however, there is a little information about the associated bacteria and its sensibility profile. Objetive: To identify and to determine the resistance pattern of aerobic and anaerobic bacteria isolated in periapendicular fluid cultures taken in patients with acute appendicitis and to establish the proportions of isolates according to the clinical phase. Materials and methods: A descriptive and prospective study was undertaken at the Hospital Universitario de San José (Bogotá, Colombia) of patients older than sixteen years of age, undergoing an open appendectomy. A sample of periappendiceal fluid was taken, which was deposited directly into aerobic and anaerobic blood culture bottles. Results: One hundred and fifty-four patients were included. The overall positivity of cultures was 87% (n=1344); 77% (n=118) for aerobes and 51% (n=79) for anaerobes. The proportion of positive cultures was lower in the uncomplicated appendicitis cases as compared to the complicated ones (80% (66/83) vs. 95%(67/71), p = 0.003). The microorganisms isolated most frequently were: Escherichia coli (53%) (n=84); Bacteroides spp. (25%) (n=25); Propionibacterium acnes (21%) (n=21); coagulase negative Staphylococci (17%) (n=27); Enterococcus spp. (11%) (n=15), and Fusobacterium spp. (11%) (n=11). The sensitivity of E.coli to ampicillin/sulbactam was 30%. The sensitivity of Bacteroides spp. to clindamycin and ampicillin/sulbactam was 91%. All anaerobe isolates were sensitive to piperacillin/tazobactam, ertapenem, meropenem and metronidazole. Conclusions: Intraoperative cultures in acute appendicits are relevant in order to determine the local epidemiological pattern and to establish prophylactic and therapeutic antibiotics for this pathology; direct inoculation in blood culture bottles allows a high recovery of microorganisms.

Role of Bacteroides fragilis in Colorectal Diseases and Prospect of Microflora Therapy / 胃肠病学

Bacteroides fragilis (BF) is a symbiotic bacterium in human intestine, and has a variety of effect on intestinal environment. BF can be divided into enterotoxigenic Bacteroides fragilis (ETBF) and nontoxigenic Bacteroides fragilis (NTBF). ETBF can lead to diarrhea, colitis, inflammatory bowel disease and colorectal cancer, while NTBF has a protective effect on intestinal homeostasis. NTBF not only can provide nutritional support for other microorganisms, but also enhance the anti-inflammatory effect of immune cells. This article reviewed the effect of BF on colorectal diseases and prospect of microflora therapy.

Inactivation of MarR gene homologs increases susceptibility to antimicrobials in Bacteroides fragilis

ABSTRACT Bacteroides fragilis is the strict anaerobic bacteria most commonly found in human infections, and has a high mortality rate. Among other virulence factors, the remarkable ability to acquire resistance to a variety of antimicrobial agents and to tolerate nanomolar concentrations of oxygen explains in part their success in causing infection and colonizing the mucosa. Much attention has been given to genes related to multiple drug resistance derived from plasmids, integrons or transposon, but such genes are also detected in chromosomal systems, like the mar (multiple antibiotic resistance) locus, that confer resistance to a range of drugs. Regulators like MarR, that control expression of the locus mar, also regulate resistance to organic solvents, disinfectants and oxygen reactive species are important players in these events. Strains derived from the parental strain 638R, with mutations in the genes hereby known as marRI (BF638R_3159) and marRII (BF638R_3706) were constructed by gene disruption using a suicide plasmid. Phenotypic response of the mutant strains to hydrogen peroxide, cell survival assay against exposure to oxygen, biofilm formation, resistance to bile salts and resistance to antibiotics was evaluated. The results showed that the mutant strains exhibit statistically significant differences in their response to oxygen stress, but no changes were observed in survival when exposed to bile salts. Biofilm formation was not affected by either gene disruption. Both mutant strains however, became more sensitive to multiple antimicrobial drugs tested. This indicates that as observed in other bacterial species, MarR are an important resistance mechanism in B. fragilis.

Identification of the alpha-enolase P46 in the extracellular membrane vesicles of Bacteroides fragilis

BACKGROUND Members of the Bacteroides fragilis group are the most important components of the normal human gut microbiome, but are also major opportunistic pathogens that are responsible for significant mortality, especially in the case of bacteraemia and other severe infections, such as intra-abdominal abscesses. Up to now, several virulence factors have been described that might explain the involvement of B. fragilis in these infections. The secretion of extracellular membrane vesicles (EMVs) has been proposed to play a role in pathogenesis and symbiosis in gram-negative bacteria, by releasing soluble proteins and other molecules. In B. fragilis, these vesicles are known to have haemagglutination and sialidosis activities, and also contain a capsular polysaccharide (PSA), although their involvement in virulence is still not clear. OBJECTIVE The aim of this study was to identify proteins in the EMV of the 638R B. fragilis strain by mass spectrometry, and also to assess for the presence of Bfp60, a surface plasminogen (Plg) activator, previously shown in B. fragilis to be responsible for the conversion of inactive Plg to active plasmin, which can also bind to laminin-1. METHODS B. fragilis was cultured in a minimum defined media and EMVs were obtained by differential centrifugation, ultracentrifugation, and filtration. The purified EMVs were observed by both transmission electron microscopy (TEM) and immunoelectron microscopy (IM). To identify EMV constituent proteins, EMVs were separated by 1D SDS-PAGE and proteomic analysis of proteins sized 35 kDa to approximately 65 kDa was performed using mass spectrometry (MALDI-TOF MS). FINDINGS TEM micrographs proved the presence of spherical vesicles and IM confirmed the presence of Bfp60 protein on their surface. Mass spectrometry identified 23 proteins with high confidence. One of the proteins from the B. fragilis EMVs was identified as an enolase P46 with a possible lyase activity. MAIN CONCLUSIONS Although the Bfp60 protein was not detected by proteomics, α-enolase P46 was found to be present in the EMVs of B. fragilis. The P46 protein has been previously described to be present in the outer membrane of B. fragilis as an iron-regulated protein.

Relationships between the enrichment of ETBF, Fn, Hp in intestinal and colorectal cancer / 中华肿瘤杂志

Objective@#To explore relationships between the enrichment of ETBF, Fn, Hp in feces, tissues and colorectal cancer.@*Methods@#Feces, lesion tissue and adjacent tissue from 24 patients with colorectal cancer and 31 patients with adenomas were collected, and we collected Feces and tissue of 20 healthy control persons. Then the copy numbers of enterotoxigenic B. fragilis (ETBF), Fusobacterium nucleatum (Fn) and Helicobacter pylori (Hp) were determined by quantitative real-time PCR. Immunohistochemical method was used to examine the expression intensity of EGFR and p53, and the relationships between different expression intensity of EGFR, p53 and the numbers of three bacterias.@*Results@#In the feces, copy numbers of ETBF and Fn were as follous: colorectal cancer group>adenomas group>healthy control group (P<0.05). Copy numbers of Hp were as follous: colorectal cancer group>healthy control group (P<0.01); adenomas group>healthy control group (P<0.01). In the tissue, copy numbers of ETBF, Fn were as follows: colorectal cancer group>adenomas group>healthy control group (P<0.05). Copy numbers of Hp were as follows: colorectal cancer group>healthy control group (P<0.01); adenomas group>healthy control group (P<0.01). Copy numbers of those three bacteria in the lesion tissue and the adjacent tissue had no significant difference. This happened both in colorectal cancer group and adenomas group. The different expression intensity of EGFR, p53 and the number of three bacteria showed no obviously statistical correlation(P>0.05).@*Conclusion@#Adenomatous polyp and colorectal cancer patients show high enrichment of ETBF, Fn and Hp in both feces and tissues. ETBF, Fn and Hp probably contribute to the development of adenomatous polyp and colorectal cancer. Trial registration Chinese Clinical Trial Registry, ChiCTR-BOC-17012509.

Metronidazole-Induced Encephalopathy in Treatment for a Thoracic Aortic Aneurysm Infected by Bacteroides fragilis / 日本心臓血管外科学会雑誌

A 77-year-old man presented with fever and back pain. Computed tomography revealed a distal arch aneurysm. Bacteroides fragilis was found in a blood culture, and we diagnosed a thoracic infected aneurysm. Because of the rapid enlargement of the aneurysm and his frailty, a TEVAR procedure was urgently performed. He left the hospital after antibiotic treatment with meropenem. However, he was re-hospitalized due to recurrence of the infection. The infection was well-controlled by treatment with intravenous meropenem, and the subsequent oral administration of metronidazole (MNZ). He was re-hospitalized again 7 weeks after discharge due to unsteady gait and articulatory disorder. MNZ-induced encephalopathy (MIE) was diagnosed because FLAIR brain magnetic resonance imaging revealed an area of high signal intensity in the bilateral basal dentate nuclei. These symptoms improved after MNZ was changed to AMPC/CVA. Fifteen months later, the patient was doing well and had no recurrence of the infection. We performed TEVAR for a patient with a thoracic aneurysm infected by B. fragilis. The recurrence of the infection was controlled by adequate antibiotic therapy, which included the administration of MNZ. However, patients who are treated with MNZ should be carefully observed to detect the development of neurological signs, as MNZ may induce encephalopathy. The early detection and withdrawal of metronidazole is important for the improvement of MIE.

Multidrug-resistant Bacteroides fragilis Isolated from a Case of Pyopneumothorax.

Aim: The aim of this case report is to present an unusual case of multidrug- resistant Bacteroides fragilis from a patient with pyopneumothorax who had a blunt injury to the thorax and got admitted in a tertiary care hospital, South India. Presentation of Case: The patient developed pyopneumothorax after a blunt injury and on admission was treated empirically with piperacillin-tazobactam and metronidazole. Following antibiotic sensitivity testing the B. fragilis strain isolated showed multidrug resistance including metronidazole. Imipenem was initiated replacing empiric therapy with a successful clinical outcome. Discussion: Bacteroides species are obligate anaerobic bacteria that are usually found in the gastrointestinal tract of the human body. Bacteroides species are the most commonly isolated anaerobic organisms from intra-abdominal lesions and rarely from intrathoracic disease conditions like pyopneumothorax. Pyopneumothorax caused by Bacteroides species is associated with high treatment failure and mortality rates in antibiotic-resistant cases. Though metronidazole is the mainstay of treating anaerobic infections, attention has to be given to the possibility of multidrug resistance when treating critical diseases. Conclusion: This case report summarizes the multidrug- resistance in Bacteroides fragilis strain isolated from a case of pyopneumothorax. The situation calls attention to the possibility of multidrug-resistance being underestimated when given as empirical therapy and institution of appropriate and timely antibiotic policy measures to prevent mortality.

Bacteroides nordii and Bacteroides salyersiae Isolated from Post-operative Peritonitis Patients

In this study, we report three cases in which two species of the Bacteroides fragilis group, 'Bacteroides nordii' and 'Bacteroides salyersiae', were isolated from peritoneal fluid cultures from post-operative peritonitis patients. The two species of the B. fragilis group were initially misidentified as B. fragilis/Bacteroides stercoris and Bacteroides ovatus by Rapid ID 32A (bioMérieux, France), and finally confirmed as B. nordii and B. salyersiae using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16s rRNA sequencing. For the identification of anaerobes, particularly B. fragilis group organisms, MALDI-TOF MS is a useful method not only because of its concordance with 16S rRNA sequencing results, but also because of its rapidity and simple procedure.

Enterotoxigenic and non-enterotoxigenic Bacteroides fragilis from fecal microbiota of children

Enterotoxigenic Bacteroides fragilis (ETBF) is an important part of the human and animal intestinal microbiota and is commonly associated with diarrhea. ETBF strains produce an enterotoxin encoded by the bft gene located in the B. fragilis pathogenicity island (BfPAI). Non-enterotoxigenic B. fragilis (NTBF) strains lack the BfPAI and usually show two different genetic patterns, II and III, based on the absence or presence of a BfPAI-flanking region, respectively. The incidence of ETBF and NTBF strains in fecal samples isolated from children without acute diarrhea or any other intestinal disorders was determined. All 84 fecal samples evaluated were B. fragilis-positive by PCR, four of them harbored the bft gene, 27 contained the NTBF pattern III DNA sequence, and 52 were considered to be NTBF pattern II samples. One sample was positive for both ETBF and NTBF pattern III DNA sequences. All 19 B. fragilis strains isolated by the culture method were bft-negative, 9 belonged to pattern III and 10 to pattern II. We present an updated overview of the ETBF and NTBF incidence in the fecal microbiota of children from Sao Paulo City, Brazil.

Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis / Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis

Introduction: Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. Objective: To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. Methods: A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Results: Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. Conclusion: From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

Introducción: Metronidazol es el antimicrobiano de elección para el manejo de infecciones anaeróbicas. Su administración requiere de dosis múltiples provocando aumento en errores medicamentosos. Debido al efecto post-antibiótico y a la actividad bactericida concentración-dependiente, la administración de metronidazol en intervalos ampliados de administración permitiría alcanzar parámetros PK/PD efectivos. Objetivo: Evaluar la probabilidad de alcanzar una relación PK/PD efectiva con la administración de 1.000 mg cada 24 h de metronidazol para infecciones por Bacteroides fragilis. Método: Se realizó un ensayo clínico sobre un grupo de voluntarios a quienes se les administró una monodosis oral de 500 y 1.000 mg de metronidazol, respectivamente. Se establecieron parámetros farmacocinéticos empleando el método trapezoidal. Se realizó una simulación de Markov que permitiera establecer la probabilidad de alcanzar una relación AUC0-24 h/CIM > 70 en infecciones por B. fragilis. Resultados: Se determinaron los valores de Cmax (24,03 ± 6,89 mg/L), t max (1,20± 0,8h) y AUC0-24 h (241,91 ± 48,14 mg*h/L), con lo cual la probabilidad de alcanzar una relación AUC0-24 h/CIM > 70 con 1.000 mg de metronidazol fue superior a 99%. Conclusión: Con la administración de 1.000 mg cada 24 h sería posible alcanzar una relación PK/PD efectiva para el tratamiento de infecciones anaeróbicas.

Antimicrobial Susceptibility of Clinical Isolates of Bacteroides fragilis Group Organisms Recovered from 2009 to 2012 in a Korean Hospital

BACKGROUND: Periodic monitoring of antimicrobial resistance trends of clinically important anaerobic bacteria such as Bacteroides fragilis group organisms is required. We determined the antimicrobial susceptibilities of clinical isolates of B. fragilis group organisms recovered from 2009 to 2012 in a tertiary-care hospital in Korea. METHODS: A total of 180 nonduplicate clinical isolates of B. fragilis group organisms were collected in a tertiary care hospital. The species were identified by conventional methods: the ATB 32A rapid identification system (bioMerieux, France) and the Vitek MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (bioMerieux). Antimicrobial susceptibility was determined by the CLSI agar dilution method. RESULTS: Imipenem and meropenem resistance rates were 0-6% for B. fragilis group isolates. The rate of resistance to piperacillin-tazobactam was 2% for B. fragilis and 0% for other Bacteroides species, but 17% for B. thetaiotaomicron isolates. High resistance rates to piperacillin (72% and 69%), cefotetan (89% and 58%), and clindamycin (83% and 69%) were observed for B. thetaiotaomicron and other Bacteroides spp. The moxifloxacin resistance rate was 27% for other Bacteroides spp. The MIC50 and MIC90 of tigecycline were 2-4 microg/mL and 8-16 microg/mL, respectively. No isolates were resistant to chloramphenicol or metronidazole. CONCLUSIONS: Imipenem, meropenem, chloramphenicol, and metronidazole remain active against B. fragilis group isolates. Moxifloxacin and tigecycline resistance rates are 2-27% and 8-15% for B. fragilis group isolates, respectively.

Metagenomic analysis of the gastric microbiota cultivable from a patient with gastritis concomitant with Barrett´s esophagus / Análisis metagenómico de la microbiota gástrica cultivable a partir de un paciente con gastritis concomitante con esófago de Barrett

Barrett’s esophagus is a distal metaplasia characterized by the transformation of squamous mucosa into columnar mucosa. This esophageal phenotype is a product not only of the chronic reflux of gastric acids, but also by microorganisms that colonize the oral cavity and stomach. Two classes of microbiota can be identified in Barrett’s esophagus; microbiota type I is associated with the normal esophagus and type II with an inflamed esophagus. The present study describes the gastric microbiota of a patient with antral gastritis concomitant with Barrett’s esophagus absent infection with Helicobacter pylori. Gastric biopsies were obtained following the protocol of Sydney and following ethical practices. The isolates were cultivated under microaerophilic conditions on Columbia Agar supplemented with IsoVitaleX™ and 7% sterile blood. Extracted DNA was sequenced using 454-GS and the results analyzed on the MG-RAST server. Gram negative isolates were found and bacteria resistant to levofloxacin, amoxicillin, tetracycline, erythromycin, and clarithromycin. The phyla Bacteroidetes, Firmicutes, Fusobacteria and Proteobacteria, the genus Bacteroides and the species group Bacteroides fragilis were most abundant. Functionally, the metabolism of carbohydrates, amino acids, and to a lesser extent, the metabolism of cofactors and vitamins were most dominant, and of which the enzymes β-glucosidase (EC 3.2.1.21), β-galactosidase (EC 3.2.1.23) and β-N-acetylhexosaminidase (EC 3.2.1.52) were most dominant. The findings of this study, because they are of only one case may probably suggest a possible pathogenic role, previously undescribed for Bacteroides fragilis, associated with human gastritis when concomitant esophageal pathology exists.

El esófago de Barrett es una metaplasia distal caracterizada por la transformación de la mucosa escamosa a mucosa columnar. Este fenotipo esofágico es producto no solo de la exposición crónica al reflujo de ácidos gástricos sino también a microbios colonizantes de la cavidad oral y del estómago. El esófago Barrett presenta 2 clases de microbiotas; la microbiota tipo I asociada con esófago normal y la tipo II a fenotipos esofágicos inflamatorios. En el presente estudio se describió la microbiota gástrica de una paciente con gastritis antral concomitante con esófago de Barrett sin infección por Helicobacter pylori y se obtuvieron biopsias gástricas siguiendo el protocolo de Sydney y estándares bioéticos. Los cultivos se hicieron en condiciones microaerofílicas en agar Columbia suplementados con isovitalex y sangre estéril al 7%. El ADN extraído fue sometido a secuenciación empleando 454 GS y las lecturas fueron analizadas en el servidor MG-RAST. Se obtuvieron aislamientos gram-negativos y resistentes a levofloxacina, amoxicilina, tetraciclina, eritromicina y claritromicina. Los Phylum Bacteroidetes, Firmicutes, Fusobacteria y Proteobacteria, el género Bacteroides y las especies de grupo Bacteroides fragilis fueron los más abundantes. Funcionalmente, el metabolismo de carbohidratos, aminoácidos y en menor grado el metabolismo de cofactores y vitaminas fueron los más dominantes; de los cuales las enzimas la β-glicosidasa (EC 3.2.1.21), β-galactosidasa (EC 3.2.1.23) y la β-N-acetilhexosaminidasa (EC 3.2.1.52) fueron las más dominantes. Estos resultados, por ser de un solo caso, solo podrían sugerir un posible papel patogénico no descrito para Bacterioides fragilis asociado con gastritis humana cuando existe patología esofágica concomitante.

Prevalence and antibiotic susceptibility of Bacteroides fragilis group isolated from stool samples in North Lebanon

Fifty one strains of the Bacteroides fragilis group were isolated from 45 fecal samples. Classical phenotypic identification showed that 16 isolates were B. thetaiotaomicron, 12 B. uniformis, 9 B. eggerthii,7 B. vulgatus,3 B. caccae,2 Parabacteroides distasonis with 1 identified B. ovatus and 1 B. fragilis. The 51 strains were tested for susceptibility against 16 antimicrobial agents and the MICs for metronidazole were determined. The tests showed that imipenem, meropenem and chloram-phenicol were the most effective antibiotics (98%, 98% and 92.16% of susceptibility, respectively) followed by ticarcillin/clavulanic acid, piperacillin/tazobactam, rifampin (88.24% susceptibility), moxifloxacin 86.27% and tigecycline 84.31%. Ofloxacin and cefotaxime were the least effective antibiotics with 27.45% and 0% of activity respectively. Only six of the 51 isolated strains were resistant to metronidazole with MICs = 64 mg/L (1 strain) and > 256 mg/L (5 strains).

Bacteroides fragilis Toxin Induces IL-8 Secretion in HT29/C1 Cells through Disruption of E-cadherin Junctions

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the beta-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (beta-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the beta-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

Posible papel de Bacteroides fragilis enterotoxigénico en la etiología de la vaginitis infecciosa / Possible role of enterotoxigenic Bacteroides fragilis in the etiology of infectious vaginitis

La vaginitis es un trastorno ginecológico frecuente producido por distintas causas, algunas de las cuales permanecen desconocidas. Bacteroides fragilis es el anaerobio más importante en bacteriología clínica. Algunas cepas son enterotoxigénicas y se asocian con síndromes intestinales y extraintestinales. Recientemente han sido aisladas de pacientes con vaginitis. En este trabajo se planteó investigar la posible asociación de B. fragilis enterotoxigénico con la vaginitis infecciosa. Fueron procesadas 265 muestras de exudado vaginal. 202 de mujeres sintomáticas y 63 mujeres sanas. La identificación de los microorganismos se realizó por métodos convencionales. En 31,2% de las pacientes sintomáticas se identificaron: Gardnerella vaginalis, Candida albicans, Mobiluncus, Mycoplasma hominis, Ureaplasma urealyticum y Streptococcus agalactiae. En 27 pacientes sintomáticas y en 5 mujeres sanas se identificó B. fragilis. Estas cepas fueron cultivadas en medio líquido e incubadas durante 48 h a 36° C en anaerobiosis. La toxicidad en los sobrenadantes se ensayó en células HT-29. 18 cepas de B. fragilis aisladas de pacientes sintomáticas fueron enterotoxigénicas, ya que indujeron alteraciones en la monocapa celular y en las células. No se identificó en mujeres sanas (P<0,05). 77,7% de las cepas de B. fragilis enterotoxigénicas no se encontraron asociadas con otros patógenos específicos. Este hecho sugiere que pudiera ser un agente causante de vaginitis, ya que el efecto de la enterotoxina sobre la E-cadherina del epitelio vaginal podría facilitar la invasión y su posible papel patógeno en la vagina. Esta es la primera investigación que asocia a Bacteroides fragilis enterotoxigénico como posible causa de vaginitis infecciosa.

Vaginitis is a common gynecologic disorder. It is due to several causes, some even unknown. Bacteroides fragilis is the most important anaerobe in clinical bacteriology, some strains of this group are notable for being enterotoxigenic and they have been associated with intestinal and extraintestinal syndromes. They have recently been isolated from patients with vaginitis. The purpose of this study was to investigate a possible association of enterotoxigenic B. fragilis with infectious vaginitis. 265 samples of vaginal exudate were processed, 202 from symptomatic patients and 63 healthy women. The identification of the microorganisms was carried out by conventional methods. In 31.2% of symptomatic patients were identified: Gardnerella vaginalis, Mobiluncus, Candida albicans, Mycoplasma hominis, Ureaplasma urealyticum and Streptococcus agalactiae. B. fragilis was identified in 27 symptomatic patients and 5 healthy women. These strains were cultivated in liquid medium and incubated during 48 h at 36°C in anaerobe chambers. Supernatant activity was assayed in HT-29 cells. Eighteen B. fragilis strains isolated from symptomatic patients were enterotoxigenic, because induced alterations in target cell morphology. It was not identified in healthy women (P<0.05). 77.7% of enterotoxigenic B. fragilis strains were not associated with other specific pathogens. This fact suggests that enterotoxigenic B. fragilis could be a cause for vaginitis. The effect of enterotoxin on E-cadherin of vaginal epithelium could facilitate invasion and its possible pathogenic role in the vagina. This is the first report that associates enterotoxigenic Bacteroides fragilis as a possible cause of infectious vaginitis.

Bacteroides fragilis endocarditis: a case report and review of literature

Endocarditis due to Bacteroides fragilis is a rare disorder. This article describes a case of Bacteroides fragilis endocarditis associated with portal and superior mesenteric venous thrombosis in a patient without preexisting valvular heart disease and review the cases of endocarditis due to this anaerobic bacterium in medical literature since 1980.