Megacolon tóxico: A propósito de un caso / Toxic Megacolon. Case Report

RESUMEN El megacolon tóxico es una enfermedad mortal, que se presenta, con mayor frecuencia, como una complicación de la inflamación intestinal, infecciones e isquemia intestinal. Se caracteriza por la presencia de diarrea sanguinolenta, distensión abdominal, signos de toxicidad sistémica y, en estudios de imagen, se observa dilatación colónica segmentaria. Para el diagnóstico, según los criterios de Jalan, se tiene en cuenta la dilatación colónica más de 6 cm, tres de los siguientes: fiebre, taquicardia, leucocitosis o anemia, y cualquiera de los siguientes criterios: hipotensión, hipovolemia, trastorno electrolítico y estado mental alterado. En este artículo, se presenta el caso de una paciente mujer que ingresa por cuadro de dolor abdominal y diarrea crónica con estudio de imagen, en la que se visualiza dilatación de todo el marco colónico. Se realizan los estudios correspondientes y se diagnostica megacolon tóxico por colitis ulcerativa, por lo que recibe tratamiento médico con evolución favorable. Es dado de alta y reingresa por shock séptico, se realizan estudios y se identifica infección por Clostridium difficile. Se inicia tratamiento antibiótico, pero presenta evolución desfavorable, lo que ocasionó el fallecimiento de la paciente. El presente caso representa la alta mortalidad de esta enfermedad.

ABSTRACT Toxic megacolon is a fatal disease, most commonly occurring as a complication of inflammatory bowel disease, infections, and intestinal ischemia. It is characterized by the presence of bloody diarrhea, abdominal distension, signs of systemic toxicity, and segmental colonic dilation is observed in imaging studies. For the diagnosis, according to the Jalan criteria, colonic dilation of more than 6 cm is taken into account, three of the following: fever, tachycardia, leukocytosis or anemia, and any of the following criteria: hypotension, hypovolemia, electrolyte disorder and altered mental status. This article presents the case of a female patient who was admitted with abdominal pain and chronic diarrhea with an imaging study showing dilation of the entire colonic framework. The corresponding studies were carried out which indicated that she had a toxic megacolon due to colitis. ulcerative, receives medical treatment with favorable evolution, is discharged and readmitted for septic shock, studies are performed and Clostridium difficile infection is identified, antibiotic treatment is started but the evolution is unfavorable, which caused the death of the patient. The present case represents the high mortality of this disease.

Tétanos: una enfermedad inmunoprevenible / Tetanus: an immunopreventable disease

Resumen El tétanos es causado por el Clostridium tetani, una bacteria ubicua que frente a condiciones de anaerobio sis puede sintetizar y liberar sus toxinas, responsables del cuadro clínico. Dado que es una bacteria que se encuentra en el suelo y en el tracto gastrointestinal de muchas especies, se trata de una enfermedad no erra dicable pero si controlable a través de la inmunización para la prevención. Las tasas de inmunización han disminuido en los últimos años, evento que se ha acentuado durante la COVID-19. Se presentan a continuación dos casos clínicos in gresados durante el año 2022. El primero es un hombre de 39 años cuya puerta de entrada fue una herida de arma de fuego conevolución favorable y el segundo caso se trata de una mujer de 83 años sin puerta de entrada clara quien falleció durante su internación en terapia intensiva. La importancia de esta presentación es mos trar la gravedad de la enfermedad, cuyavaloración es principalmente clínica y no debe escapar al algoritmo de diagnósticos diferenciales, acentuando que se debe instaurar el tratamiento de forma precoz o frente a la duda consultar con un centro especializado. Asímismo, es importante revisar las tasas de inmuni zación en nuestro país y los cambios que se presentaron durante la pandemia, teniendo en cuenta, como se ha expuesto previamente, se trata de una enfermedad in munoprevenible.

Abstract Tetanus is an infectious disease caused by a ubiqui tous bacterium Clostridium tetani, that synthesizes and releasesa potent neurotoxin under anaerobic conditions, which is responsible for the clinical manifestations. As it is found in soil contaminated with animal and human excreta, it is difficult to eradicate but it may be prevented by immunization. Immunization rate has decreased in the last years, especially during the COVID-19 pandemic. We report two cases of tetanus, attended during 2022. A 39-year-old man whose entry route was a gunshot wound and he was discharged from the intensive care unit (ICU) and a second case of an 83-year-old woman with unknown entry point, who died during her ICU stay. The cases reported highlight that it is a life-threatening disease, its diagnosis is mainly clinical and it should be in the algorithm of differential diagnoses. We emphasize about the prompt treatment administration or consulta tion to a specialized healthcare center. The importance of this presentation is to show the severity of the dis ease, whose assessment is mainly clinical and should not escape the algorithm of differential diagnoses, em phasizing that treatment should be instituted early or when in doubt consult a specialized center. In addition to this, it is important to check theimmunization rate in our country, especially during thepandemic, becauseit is a vaccine-pre ventable disease.

Neonatal Tetanus: demographics, clinical management and outcomes of A Study of 7 Cases in Afghanistan

This study aims to study the demographics, treatment and outcome of neonatal tetanus patients managed at Nangarhar Regional Hospital Afghanistan from June 2019-January 2021. Seventeen neonates were studied. All presented with fever, poor sucking and limb stiffness, with a history of unsterile delivery and uncertain maternal tetanus immunity status. Low-resource settings continue to report high mortality from neonatal tetanus, due to lack of sophisticated management modalities like neuromuscular blockade and invasive ventilation [20-23].The age group of mothers 21-25 of admitted neonates shows high frequency i.e 42.85%. Education of mother of admitted neonates was Primary education i.e 57.14%. 71.42 % (5) mothers not vaccinated. The vaccination awareness should be implemented in community by organising various awareness camp town wise. Government should implement the education mandatory and free for below poverty class and females.

Bacteriemia por Clostridium tertium en un paciente con cirrosis hepática / Clostridium tertium bacteremia in patient with liver cirrhosis

Resumen Clostridium tertium es una bacteria de la familia Clos tridiaceae que se puede encontrar colonizando el tracto gastrointestinal. A diferencia de otros miembros de su familia, no produce exotoxinas. Fue descripto por prime ra vez en 1917 y en el año 1963 se pudo establecer como patógeno en humanos. Desde entonces, se han reportado casos principalmente en huéspedes inmunosuprimi dos, prevalentemente con foco primario abdominal. Se describe el caso de un hombre de 48 años de edad con antecedentes de cirrosis e infección por virus de la hepatitis C, presentó una hernia umbilical atascada que requirió resección y anastomosis intestinal, con cultivos de líquido abdominal y hemocultivos positivos para Clostridium tertium. Este caso es de importancia clínica por la baja prevalencia de este germen, la posibilidad de resistencia a los esquemas antibióticos usuales y de subdiagnóstico del microorganismo dada su similitud morfológica y de crecimiento con Bacillus o Lactobacillus.

Abstract Clostridium tertium is a bacterium of the Clostridiaceae family which can be found colonizing the gastrointes tinal tract. Unlike other members of its family, it does not produce exotoxins. It was described for the first time in 1917 and in 1963 it was established as a pathogen in humans. Since then, cases have been reported mainly in immunosuppressed hosts, predominantly with primary focus at the abdominal level. The case of a 48-year-old man with a history of cirrhosis and hepatitis C virus infection is described. He presented an obstructed um bilical hernia that required intestinal resection and anastomosis, with positive blood and abdominal fluid cultures for Clostridium tertium. This case is of clinical importance due to the low prevalence of this germ, the possibility of resistance to usual antibiotic regimens and its sub diagnostic given the morphological and growth similarities with Bacillus or Lactobacillus.

Trasplante de microbiota fecal como alternativa de tratamiento por infecciones de clostridoides difficile / Fecal microbiota transplantation as a treatment alternative for clostridoides difficile infections / Transplante de microbiota fecal como tratamento alternativo para infecções clostridioides difficile

La infección por Clostridioides difficile es una amenaza para la salud pública, está asociada a la atención médica, cuya complicación más frecuente es la infección recurrente, con tasas de hasta el 60% después del tercer episodio. Las opciones de tratamiento para la recurrencia de esta infección son limitadas. Una gran paradoja es tratar una infección asociada a antibióticos con más antibióticos, por ello, la piedra angular en el manejo de esta infección es la restauración de la microbiota intestinal mediante el trasplante de microbiota fecal. Objetivo. Determinar la eficacia y seguridad del trasplante de microbiota fecal para el tratamiento de la infección recurrente por Clostridioides difficile. Metodología. Se realizó una revisión bibliográfica narrativa de la literatura científica en las bases de datos PubMed y Cochrane Library empleando los Descriptores en Ciencias de la Salud (DeCS) y Medical Subject Headings (MeSH), junto con los operadores booleanos "AND/Y", "OR/O"; donde se recopilaron los estudios que cumplieron con los criterios de inclusión. Conclusión. Se concluyó que el trasplante de microbiota fecal en la infección recurrente por Clostridioides difficile es un tratamiento eficaz y seguro, con eventos adversos mínimos, aunque la seguridad a largo plazo no está bien establecida.

Clostridioides difficile infection is a public health threat, is associated with health care, the most common complication of which is recurrent infection, with rates of up to 60% after the third episode. Treatment options for recurrence of this infection are limited. A great paradox is to treat an antibiotic-associated infection with more antibiotics; therefore, the cornerstone in the management of this infection is the restoration of the intestinal microbiota by fecal microbiota transplantation. Objective. To determine the efficacy and safety of fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection. Methodology. A narrative bibliographic review of the scientific literature was carried out in the PubMed and Cochrane Library databases using the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH), together with the Boolean operators "AND/Y", "OR/O"; where the studies that met the inclusion criteria were collected. Conclusion. It was concluded that fecal microbiota transplantation in recurrent Clostridioides difficile infection is an effective and safe treatment, with minimal adverse events, although long-term safety is not well established.

A infecção por Clostridioides difficile é uma ameaça à saúde pública associada ao cuidado com a saúde, cuja complicação mais comum é a infecção recorrente, com taxas de até 60% após o terceiro episódio. As opções de tratamento para infecções recorrentes são limitadas. Um grande paradoxo é tratar uma infecção associada a antibióticos com mais antibióticos, portanto, a pedra fundamental no manejo desta infecção é a restauração da microbiota intestinal através do transplante da microbiota fecal. Objetivo. Determinar a eficácia e segurança do transplante de microbiota fecal para o tratamento de infecções recorrentes por Clostridioides difficile. Metodologia. Uma revisão bibliográfica narrativa da literatura científica foi realizada nas bases de dados da Biblioteca PubMed e Cochrane utilizando os Descritores de Ciências da Saúde (DeCS) e os Títulos de Assuntos Médicos (MeSH), juntamente com os operadores booleanos "AND/Y", "OR/O"; onde foram compilados os estudos que preenchiam os critérios de inclusão. Conclusão. Concluiu-se que o transplante de microbiota fecal em infecção recorrente por Clostridioides difficile é um tratamento eficaz e seguro com o mínimo de eventos adversos, embora a segurança a longo prazo não esteja bem estabelecida.

Fulminant endogenous panophthalmitis caused by Clostridium septicum infection / Panoftalmite endógena fulminante por infecção por Clostridium septicum

ABSTRACT We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.

RESUMO Este é o relato de um caso incomum de panoftalmite endógena fulminante por Clostridium septicum. Um paciente do sexo masculino, 74 anos, apresentou amaurose súbita no olho direito, que em poucas horas evoluiu para celulite orbitária, endoftalmite, isquemia do segmento anterior e perfuração secundária do olho. Foi realizado um estudo diagnóstico completo, que incluiu uma tomografia computadorizada com contraste cranial e orbital, um exame de ressonância magnética, hemocultura e hemograma completo. Nenhum agente causal foi identificado. A infecção por Clostridium septicum causou uma panoftalmite gasosa fulminante. Apesar do tratamento com antibióticos de amplo espectro, foi necessário eviscerar o globo ocular. O estudo de seguimento mostrou um adenocarcinoma de cólon como a origem da infecção. A panoftalmite por Clostridium septicum é um tipo raro, mas muito agressivo de infecção orbitária. Essa infecção deve sugerir a busca por um processo neoplásico no trato gastrointestinal, em muitos casos não diagnosticado anteriormente.

Comparison of biological characteristics of major epidemic strains of Clostridium difficile from nosocomial infectious diarrhea / 中华检验医学杂志

Objective:This work aims to investigate the virulence features, spore formation and the resistance mechanisms of major sequence types (STs) of clinical Clostridium difficile isolates from nosocomial infectious diarrhea. Methods:Clostridium difficile isolates were prospectively collected from 816 loose stool samples of in patients with antibiotic associated diarrhea at the Beijing Friendship Hospital of Capital Medical University from September 2017 to September 2019. The main ST types ST81 (26 strains), ST8 (15 strains) and ST42 (14 strains) of C. difficile were used as experimental strains. The polymerase chain reaction (PCR) and enzyme-linked immunoassay (ELISA) were performed to detect toxin genes and toxin production of different C. difficile ST types, respectively. The count of the colony forming units (CFU) of the strains as conducted by using the brain-heart infusion (BHI) agar plates. The antimicrobial resistance patterns of the strains to eleven kinds of antibiotics were determined by agar dilution method. The antimicrobial resistance genes: gyrA, gyrB and ermB were amplified and sequenced from the stains. Mutations in the resistance genes were analyzed by sequencing. Measure data was compared by Kruskal Wallis Test, differences in the resistance rates in three group were compared using Fisher exact test. Results:ST81 strains were identified as the tcdA-tcdB+/ cdtA-cdtB-toxin type, ST8 and ST42 strains belonged to tcdA+tcdB+/ cdtA-cdtB-toxin type. The toxin production of ST42 strains (41.9) were higher than ST8 (2.4) and ST81 groups (0.83) (all P<0.001). The number of spore quantities of ST81, ST8 and ST42 strains were 494×10 5CFU/ml, 160×10 5CFU/ml and 166×10 5CFU/ml, respectively. The spore quantities of ST81 strains were much higher than that of ST81 and ST42 strains (all P<0.001). From the in vitro susceptibility test, 100% (26/26) ST81 strains were featured as multi-drug resistant (MDR), and they were resistant to moxifloxacin, ceftriaxone, erythromycin and clindamycin. The resistance rates of ST8 strain to moxifloxacin, erythromycin and clindamycin were 9/15, 11/15 and 11/15, respectively. ST81 strains had higher resistance rates to moxifloxacin, clindamycin and erythromycin, compared to ST8 strains ( P=0.001, P=0.005 and P=0.005). All ST42 strains were susceptible to ceftriaxone and 3/14 ST42 strains were resistant to moxifloxacin. ST81 strains had higher resistance rates to ceftriaxone and moxifloxacin than the ST42 strains (both P<0.001). The positive rate of ermB in ST81 strains (100%, 26/26) were higher the ST8 strains (11/15) ( P<0.005). Amino acid mutation analysis showed that ST81and ST8 stains had one amino acid substitution in both GyrA and GyrB, but the amino acid substitutions were different in GyrB between two ST types. ST81 strains had two point-mutations: Thr82 replaced by Ile in GyrA, and Asp426 replaced by Val in GyrB. ST8 strains had point-mutation: Thr82 replaced by Ile in GyrA; Asp426 replaced by Asn in GyrB. For ST42 strains, Thr82 was replaced by Ile in GyrA. Conclusions:ST81 and ST42 strains were MDR. ST81 had higher spore ability, whereas ST42 strains had more virulence. ST81 strains and most of ST8 strains had high level of fluoroquinolones resistance. It is important to supervise persistently these three ST genotypes to prevent further dissemination.

Protective effect of Clostridium butyricum on renal tissue in db/db mice and its mechanism / 中华内分泌代谢杂志

Objective:To investigate the effect of Clostridium butyricum on renal tissue of db/db mice and to explore its mechanism. Methods:Fourteen-week-old db/db mice were divided into db/db group( n=10) and db/db+ Cb group( n=7) according to random number table method. Age-matched db/m mice were selected as the normal control group. The db/m and db/db mice were administered 0.9% sodium chloride solution by gavage, while the db/db+ Cb mice were administered an equivalent amount of Clostridium butyricum solution by gavage for 8 weeks. Serum creatinine , fasting blood glucose, urinary albumin to creatinine ratio(ACR) and other biochemical indicators were also detected. HE staining was used to observe the pathological changes of kidney tissue. The expressions of peroxisome proliferators-activated receptor γ coactivator-1α(PGC-1α) mRNA were detected by realtime PCR, while the expressions of nuclear factor-κB(NF-κB), glucagon-like peptide 1 receptor(GLP-1R), and adenosine monophosphate-activated protein kinase(AMPK) in kidney tissue were determined by immunohistochemistry and Western blotting. The levels of intestinal flora, serum and fecal short-chain fatty acids(SCFAs) were measured by 16S rRNA, liquid chromatograph-mass spectrometer, and gas chromatograohy-mass spectrometry respectively. Results:Compared to db/db mice, db/db+ Cb mice showed improvement in general condition after supplementation with Clostridium butyricum. Fasting blood glucose, blood urea nitrogen, albumin-to-creatinine ratio(ACR), blood creatinine, and levels of interleukin-6(IL-6) in kidney tissue were reduced(all P<0.05). The pathology showed various degrees of amelioration of kidney tissue injury in mice. The expression of PGC-1α mRNA increased in kidney tissue( P<0.05). Decreased expression of NF-κB protein, as well as increased expression of GLP-1R and phosphorylated(p-)AMPK/AMPK protein(all P<0.05) were detected in kidney tissues. Clostridium butyricum modulated the composition of the gut microbiota with elevated total SCFAs in blood and feces. Conclusion:Clostridium butyricum increased the expression of GLP-1R in kidney tissue, promoted AMPK phosphorylation, and alleviated renal tissue damage in mice. This suggests that it may be associated with regulating the abundance of SCFA-producing bacterial populations.

Etiology and prognostic factors of necrotizing enterocolitis in infants after neonatal period with hematochezia / 中国小儿急救医学

Objective:To analyze the etiology and prognostic factors of necrotizing enterocolitis(NEC) in infants after neonatal period with hematochezia.Methods:The clinical data of 62 infants older than 28 days with NEC and hematochezia diagnosed at Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2021 were retrospectively analyzed, summarizing the etiology of NEC in this age group and analyze the factors affecting the prognosis of NEC.According to IgE detection results of food allergens, the infants were divided into milk protein positive group and milk protein negative group.According to the absolute value level of peripheral blood eosinophils, they were divided into increased eosinophils group(≥0.5×10 9/L) and normal eosinophils group(<0.5×10 9/L). They were divided into three groups according to co-infection: NEC group(no co-infection), NEC+ clostridium difficile associated diarrhea(CDAD) group, and NEC+ other infection group(salmonella infection or sepsis). According to different feeding methods, they were divided into normal amino acid group(osmotic pressure 310 mOsm/L), diluted amino acid group(osmotic pressure 233 mOsm/L), and deep hydrolysis group(osmotic pressure 185 mOsm/L). The relief time of clinical symptoms, the recovery time of intestinal gas accumulation, feeding time to achieve physiological requirements, and the length of hospital stay in each group were compared. Results:Among 62 cases, there were 27 males and 35 females.The median age of onset was 1.4(1.2, 2.3) months.The median birth weight was 3.2(2.9, 3.4)kg.Full-term infants accounted for 87.1%.Cesarean accounted for 62.9%.Fifty-three patients(85.5%)had allergic symptoms.Thirteen patients(21.0%)had family history of allergy.Cow milk protein allergy was diagnosed in 29 cases.Thirty-two cases(51.6%) had elevated peripheral blood eosinophils.The hospitalization time of milk protein positive group was longer than that of negative group( P=0.047). The clinical remission rate after hypoallergenic formula feeding for 1 day of increased eosinophils group was higher than that of normal eosinophil group(100.0% vs.65.0%, P=0.002). Ten patients(16.1%)were complicated with clostridium difficile infection, two patients(3.2%) with salmonella enteritis, and four patients(6.5%) with sepsis.Both the hospital stay and feeding time to achieve physiological requirements of NEC+ other infection group were longer than the other two groups( P<0.05). NEC+ CDAD group had a higher rate of repeated hospitalizations(40.0%, P=0.004). The mean recovery time of intestinal gas accumulation was(4.5±2.9)days.After(3.9±3.0)days, hypoallergenic formula feeding started.After one day of feeding, the clinical remission rate was 79.0%.The average time to achieve physiological requirements was(5.8±3.2)days.The clinical symptom relief time of diluted amino acid group was shorter( P=0.006), but there was no statistical difference in feeding time to achieve physiological requirements and hospitalization time between each group( P>0.05). Conclusion:Cow′s milk protein allergy and infection(especially CDAD)are closely related to the occurrence and development of NEC after neonatal period with hematochezia.The administration of diluted amino acid-based formulae close to the osmotic pressure of breast milk and targeted anti-infective therapy could shorten the clinical remission time of NEC and reduce the risk of repeated hospitalization.

Design, synthesis and biological evaluation of 8-hydroxyquinoline derivatives as potential clostridium difficile antibiotics / 药学实践杂志

Objective To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection (CDI) because of the high recurrence rate. Methods A series of 8-hydroxyquinoline derivatives were designed and synthesized based on 8-hydroxyquinoline scarffold. Results The activity test against C. difficile showed that most of the molecules exhibited good antibacterial activity against C. difficile, and compound 6f showed attractive anti-C. difficile activity. Conclusion A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found, which could be used as good lead compounds for further development.

A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia

@#Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.

Management of diarrhea after kidney transplantation / 器官移植

Diarrhea is a frequent complication after kidney transplantation, which is a common clinical manifestation of prevalent diseases following multiple types of organ transplantation. The common causes of diarrhea after kidney transplantation include adverse reactions of immunosuppressants, infectious diseases and de novo postoperative inflammatory bowel disease, etc. Diarrhea could seriously affect the quality of life of kidney transplant recipients, and may lead to allograft dysfunction or even death of recipients. Because the causes of diarrhea after kidney transplantation are complicated and probably overlap with each other, along with individual differences among recipients, the etiological diagnosis and targeted treatment of diarrhea after kidney transplantation should follow the principles of gradual and phased treatment. In this article, the epidemiology and harm, common causes and management strategies of diarrhea after kidney transplantation were summarized, aiming to deepen the clinicians' understanding and enhance the diagnosis and treatment levels of diarrhea after kidney transplantation, thereby improving the quality of life and prognosis of kidney transplant recipients.

Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

Aetiology of hospital-acquired diarrhoea in under-five children from an urban hospital in East Delhi, India

Background & objectives: Majority of the studies of hospital-acquired diarrhoea conducted in Western countries have focused on the detection of Clostridium difficile in stool samples. Limited Asian and Indian literature is available on hospital-acquired diarrhoea. This study was aimed to describe the aetiological profile for hospital-acquired diarrhoea in children aged below five years. Methods: One hundred children aged one month to five years who developed diarrhoea (?3 loose stools for >12 h) after hospitalization for at least 72 h were enrolled. Children who were prescribed purgatives or undergoing procedures such as enema and endoscopy or those with underlying chronic gastrointestinal disorders such as celiac disease and inflammatory bowel disease were excluded from the study. Stool samples from the enrolled children were subjected to routine microscopic examination, modified Ziel- Nielson (ZN) staining for Cryptosporidium and culture for various enteropathogens. Multiplex PCR was used to identify the strains of diarrhoeagenic Escherichia coli. Rotavirus detection was done using rapid antigen kit. Toxins (A and B) of C. difficile were detected using enzyme immunoassay. Results: Of the 100 samples of hospital-acquired diarrhoea analysed, diarrhoeagenic E. coli (DEC) was found to be the most common organism, detected in 37 per cent of cases (enteropathogenic E. coli-18%, enterotoxigenic E. coli-8%, enteroaggregative E. coli-4% and mixed infections-7%). Cryptosporidium was detected in 10 per cent of cases. Rotavirus was detected in six per cent and C. difficile in four per cent of cases. Interpretation & conclusions: The findings of this study suggest that the aetiological profile of hospital- acquired diarrhoea appears to be similar to that of community-acquired diarrhoea, with DEC and Cryptosporidium being the most common causes. The efforts for the prevention and management of hospital-acquired diarrhoea should, thus, be directed towards these organisms.

Perforación colónica y sepsis fulminante asociada a Clostridium septicum como presentación de un cáncer de colon / Colonic perforation and sepsis associated with Clostridium septicum as clinical presentation of colon cancer

Resumen La asociación entre algunas infecciones bacterianas y cáncer de colon está bien documentada. La más descrita es la infección por Streptococcus bovis. Otra bacteria relacionada a neoplasias intestinales es Clostridium septicum. Presentamos el caso clínico de un varón de 62 años que consultó por dolor abdominal, diarrea y fiebre. Se realizó una tomografía computada de abdomen y pelvis que evidenció un engrosamiento de las paredes del ciego con una aparente solución de continuidad en su borde libre. En una laparotomía exploradora se confirmó la presencia de peritonitis y perforación cecal, siendo sometido a una hemicolectomía derecha e ileostomía terminal. El estudio histopatológico reveló la presencia de un adenocarcinoma de tipo células en anillo de sello asociado a isquemia. Los hemocultivos fueron positivos a C. septicum. El paciente falleció por una sepsis fulminante.

Abstract The association between some bacterial infections and colon cancer is well documented. The most described is Streptococcus bovis infection. Another bacteria related to intestinal neoplasms is Clostridium septicum. We present the case of a 62-year-old man who consulted for abdominal pain associated with diarrhea and fever. A computed tomography scan of the abdomen and pelvis was performed, which revealed thickening of the cecum walls with an apparent break in continuity at its free edge. An exploratory laparotomy was performed which confirmed the presence of peritonitis and cecal perforation. A right hemicolectomy and terminal ileostomy were performed. The histopathological study revealed the presence of signet ring cell type adenocarcinoma associated with ischemia. The blood cultures results demonstrated the presence of C. septicum. The patient died due to fulminant sepsis.

Clostridium Difficile is associated with High Mortality among Cirrhotics in India

Background: To assess the prevalence and impact of Clostridium difficile infection (CDI) in hospitalized patients with cirrhosis in India. Methods: In this prospective observational study from June 2015 to March 2016, all hospitalized patients with cirrhosis and acute diarrhea at the time of admission or during hospitalization were included. We studied hospitalized patients with cirrhosis without diarrhea during the same period to detect asymptomatic colonizers.Stool samples were tested for CDI, bacterial cultures, and parasite microscopy in patients with diarrhea.CDI was detected using a stool PCR test that detects the pathogenicity locus of toxigenic Clostridium difficile gene. We analysed the impact of CDI on hospital outcomes and also assessed the risk factors for acquiring CDI. Result: Among 92 hospitalized cirrhotic patients with acute diarrhea [male: 74; median age: 50 (range 19 to 80) years; Child’s class A: B: C: 8:41:43; median MELD score: 18 (range 6 to 44)], 6 (6.5%) had CDI by positive stool PCR. Use of antibiotics (100% CDI Vs 55.8% non-CDI, p= 0.04) and steroids (50% CDI vs 10.5% non-CDI, p =0.028) emerged as risk factors for CDI among cirrhosis patients. Two of the 6 patients (33.3%) with CDI as compared to 6/86 patients (7%) with no CDI died (p-value: 0.08).There were no asymptomatic colonizers amongst 35 hospitalized cirrhosis patients without diarrhea.Conclusions: C. difficile, although uncommon, was an important cause of mortality in cirrhosis patients hospitalized with diarrhea in India.Prior use of antibiotics or steroids were identified as risk factors for CDI.

Development of a double-antibody sandwich ELISA targeting the receptor binding domain of TcdB toxin of ST11 type Clostridium difficile of porcine origin / 生物工程学报

Clostridium difficile is an important zoonotic intestinal pathogen, which is widely present in humans and a variety of animals. The ST11 type C. difficile is one of the most widespread and harmful subtypes in the world. As a large country in pig farming, China lacks efficient methods for detecting C. difficile of porcine origin, leaving hidden dangers for the prevention and control of C. difficile. The aim of this study was to develop a specific and sensitive double-antibody sandwich ELISA for the epidemiological investigation of ST11 type C. difficile of porcine origin. Firstly, a 97 kDa receptor binding domain (RBD) was expressed in a prokaryotic host and purified. A hybridoma cell line AE2D3 capable of stably secreting monoclonal antibody targeting the RBD was screened, and the antibody subtype was determined to be IgG2b (κ). Secondly, a double antibody sandwich ELISA method was developed, where the monoclonal antibody targeting the RBD was used as a detection antibody, and the rabbit polyclonal antibody was used as a capture antibody. The chessboard method was used to determine the matching concentration of the capture antibody and the detection antibody, the antigen coating conditions, the blocking conditions, the incubation conditions for detection antibody and samples to be tested, as well as the reaction conditions of HRP-conjugated and reaction conditions of TMB chromogenic solution. The negative cutoff OD450 was 0.152, and no cross-reaction with 13 strains of non-ST11 type C. difficile was found. The minimum detection concentration of RBD was 8.83 ng/mL. This specific and sensitive double-antibody sandwich ELISA provides a reliable serological detection method for epidemiological investigation of the ST11 type C. difficile in pig industry.

Immune effects of Clostridium difficile toxoid B vaccine formulated with different mucosal adjuvants through microneedle immunization / 中华微生物学和免疫学杂志

Objective:To investigate the immune effects of Clostridium difficile toxoid B (CdtB) vaccine formulated with different mucosal adjuvants through microneedle immunization, and to provide ideas for the prevention and treatment of Clostridium difficile infection. Methods:CdtB vaccine was prepared with purified Clostridium difficile toxin B(TcdB) after formaldehyde detoxification. Female BALB/c mice were immunized with different doses of vaccine alone or in combination with mucosal adjuvants. The titers of specific serum IgG and fecal IgA were detected at 0 d, 7 d, 14 d, 28 d and 42 d after immunization. The protective effects of CdtB vaccine were evaluated by cell neutralization assay and Clostridium difficile challenge infection. Results:(1) With the increase of immune dose, the mice immunized with CdtB vaccine alone by microneedle not only produced better serum specific IgG, but also had higher level of IgA in feces. (2) When the mice were immunized with CdtB vaccine containing LT or CTB adjuvant by microneedle, the trend of serum specific IgG titer in each group increased with the increase of immune dose, especially in the group containing LT adjuvant. There were significant differences in the trend of specific IgA titer in feces between the adjuvant groups and the group without adjuvant, but the adjuvant effect was not obvious. (3) No significant difference in serum IgG titer was observed between the mice immunized with 10 μg CdtB by microneedle or intraperitoneal injection, but microneedle immunization significantly increased fecal IgA level. (4) The neutralization titers of specific antibodies in mouse serum after immunization and the test results of challenge protection in mice confirmed that the use of CdtB vaccine had certain protective effects.Conclusions:CdtB vaccine had better immune effects in mice through microneedle immunization, but the adjuvant effects of LT and CTB were not significant.

Advances in application of volatile organic compounds in the rapid detection of clostridium difficile infection / 国际儿科学杂志

Clostridium difficile infection(CDI)is a global public health issue and one of the most common pathogenic infections in the community and hospitals, causing varying degrees of diarrhea and pseudomembranous colitis.The current CDI diagnosis is based on the detection of clostridium difficile(CD)associated toxins or toxin encoding genes in patients′ stool, but these traditional microbiological techniques have limitations that may delay disease diagnosis.In clinical and research, CD has a distinct odor "horse barn odor" , which is caused by the volatile organic compounds(VOCs). VOCs in human breath, blood, urine and feces have recently received increased attention as potential noninvasive diagnostic biomarkers for a wide range of diseases, including infectious diseases and digestive tract disorders.It was discovered that VOCs from CD, with their potential characteristic VOCs, contributed to the rapid diagnosis of CDI.In this paper, we review VOCs and their application in the rapid detection of CDI.