Surto de botulismo em bovinos leiteiros associado ao consumo de resíduo de fecularia: relato de caso / Botulism outbreak in dairy cattle associated with cassava by-product intake: case report / Brote de botulismo en ganado lechero asociado al consumo de residuos de almidón: informe de un caso

O resíduo de fecularia é um subproduto da agroindústria utilizado com frequência na alimentação de bovinos leiteiros pelo alto teor energético e baixo custo. No entanto, possui características propícias ao desenvolvimento de microrganismos patogênicos como o Clostridium botulinum, causador do botulismo. Este relato é o primeiro na literatura consultada a descrever um surto de botulismo em uma propriedade de bovinos leiteiros devido ao consumo de massa de mandioca, alimento ofertado em muitas propriedades do Oeste do Paraná. 16 animais, de um total de 24 morreram em um período de 14 dias, com sinais clínicos de respiração abdominal, sialorreia, paresia de membros pélvicos, decúbito esternal seguido de lateral permanente, diminuição dos tônus mandibular e lingual e morte em até 48 horas. Os animais não eram vacinados para clostridioses e recebiam o resíduo em cocho coletivo. O diagnóstico foi baseado no histórico, na avaliação das condições de armazenamento do alimento na propriedade, no exame físico e na ausência de lesões macroscópicas e histológicas. Conclui-se que o resíduo de fecularia deteriorado é um substrato propício para desenvolvimento do C. Botulinum sendo um alimento passível de provocar surtos de botulismo em bovinos leiteiros com alta morbidade e letalidade.

Cassava is an industry by-product waste used to feeding cattle due to its low cost and high energy. However, this food presents characteristics to development of pathogenic microorganisms such as Clostridium botulinum causer of botulism. This disease results from the ingestion of preformed neurotoxins that act at the neuromuscular junctions causing flaccid paralysis of striated muscles. This is the first report to describe botulism due the intake of cassava by-product (tapioca waste), a common food offered in the west of Parana State. 16 dairy cattle died from a total of 24 animals in 14 days. The clinical signs were dyspnea with abdominal pattern, sialorrhea, pelvic limb paresis, decreased mandibular and tongue tonus and permanent sternal progressing to lateral decubitus and death until 48 hours after the onset of signs. The diagnosis was based on anamnesis, evaluation of food storage conditions, clinical examination, and the absence of macroscopic and histology lesions. It was concluded that cassava by-product has conditions to the development of Clostridium botulinum and can cause botulism outbreak with high morbidity and lethality.

El residuo de almidón es un subproducto de la agroindustria que suele utilizarse para alimentar al ganado lechero por su alto contenido energético y su bajo coste. Sin embargo, tiene características favorables para el desarrollo de microorganismos patógenos como Clostridium botulinum, causante del botulismo. Este informe es el primero en la literatura que describe un brote de botulismo en una hacienda de ganado lechero debido al consumo de pasta de mandioca, alimento ofrecido en muchas propiedades del oeste de Paraná. 16 animales, de un total de 24, murieron en un período de 14 días, con signos clínicos de respiración abdominal, sialorrea, paresia de los miembros pélvicos, decúbito esternal seguido de decúbito lateral permanente, disminución del tono mandibular y lingual y muerte en 48 horas. Los animales no estaban vacunados contra la clostridioses y recibían sus desechos en un comedero comunitario. El diagnóstico se basó en la anamnesis, la evaluación de las condiciones de almacenamiento de los alimentos en la propiedad, el examen físico y la ausencia de lesiones macroscópicas e histológicas. Se concluye que el residuo de almidón descompuesto es un sustrato favorable para el desarrollo de C. botulinum y es un alimento que puede causar brotes de botulismo en ganado lechero con alta morbilidad y letalidad.

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.

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.

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.

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.

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.

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.

Experience of a gastroenterology center in fecal microbiota transplantation in the treatment of Clostridioides Difficile / Experiência de um centro de gastroenterologia em transplante de microbiota fecal no tratamento de Clostridioides difficile

Background: The treatment of Clostridioides difficile is based on an antibiotics cycle, but for individuals who have more than two recurrences, fecal microbiota transplantation can be considered as a therapeutic option. Objective: To describe the technique and results of fecal microbiota transplantation performed for recurrent infection by Clostridioides difficile. Methods: Retrospective, cross-sectional study based on a review of medical records of patients undergoing transplantation of fecal microbiota. Data were obtained on the criteria used to select the donor, the preparation of stools in the laboratory and the method of delivery of the material offered, as well as information regarding the characteristics of the recipient, such as: gender, age, comorbidities, hospitalizations, use of antibiotics prior to infection, clinical presentation, diagnosis and treatments performed for Clostridioides difficile. After transplantation, data on efficacy, outcome, follow-up time and procedure complications were considered. Results: Between 2012 and 2019, 11 patients underwent fecal microbiota transplantation. The use of antibiotics prior to infection occurred in 9 patients, no patient was hospitalized in the previous 6 months due to another etiology. All had at least 2 cycles of vancomycin for recurrent disease. Of the total of 11 patients, 2 required 2 infusions and 1 patient required 3, totaling 15 fecal microbiota transplants. The success rate was 81.8% with only one infusion and 90.9% resolution considering patients who needed more than one infusion. Conclusion: Fecal microbiota transplantation is a feasible therapy with resolution in 90.9% of cases as a treatment for recurrent Clostridioides difficile infection.

Contexto: O tratamento do Clostridioides difficile é baseado em ciclo antimicrobiano, mas para os indivíduos que apresentam mais de duas recorrências, pode-se considerar o transplante de microbiota fecal como opção terapêutica. Objetivo: Descrever a técnica e os resultados do transplante de microbiota fecal realizados para infecção recorrente por Clostridioides difficile. Métodos: Estudo retrospectivo, transversal, baseado em revisão de prontuários de pacientes submetidos ao transplante de microbiota fecal. Foram obtidos dados sobre os critérios empregados para seleção do doador, o preparo das fezes e o método de entrega do material, além de informações referentes às características do receptor, como: sexo, idade, comorbidades, internamentos, uso de antimicrobiano prévio à infecção, apresentação clínica, diagnóstico e tratamentos realizados para o Clostridioides difficile. Após o transplante, dados sobre eficácia, desfecho, tempo de seguimento e complicações do procedimento foram considerados. Resultados: Entre 2012 e 2019, 11 pacientes foram submetidos ao transplante de microbiota fecal. O uso de antimicrobiano prévio à infecção ocorreu em 9 pacientes, nenhum paciente internou nos 6 meses anteriores por outra etiologia. Todos fizeram pelo menos 2 ciclos de vancomicina para doença recorrente. Do total de 11 pacientes, 2 necessitaram de 2 infusões e 1 paciente necessitou de 3, totalizando 15 transplantes de microbiota fecal. O sucesso foi de 81,8% com apenas uma infusão e resolução de 90,9% considerando pacientes que necessitaram de mais de uma infusão. Conclusão: O transplante de microbiota fecal é uma terapia factível e com resolução em 90,9% dos casos como tratamento de infecção recorrente por Clostridioides difficile.

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.

The protective effects of dietary Clostridium butyricum supplementation on hepatic ischemia reperfusion injury in rats

Purpose: This study investigated the effects of oral administration of Clostridium butyricum (C. butyricum) on inflammation, oxidative stress, and gut flora in rats with hepatic ischemia reperfusion injury (HIRI). Methods: The rats from C. butyricum group were given C. butyricum for 5 days. Then, hepatic ischemia for 30 min and reperfusion for 6 h were performed in all the rats. After the animals were sacrificed, alanine transaminase (ALT), aspartate aminotransferase (AST), lipopolysaccharide (LPS) in serum, short-chain fatty acids (SCFAs), and gut microbiota composition in feces, and malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), Toll-like receptor 4 (TLR4), nuclear factor-kappa Bp65 (NF-κBp65) and histological analysis in the liver were performed. Results: The rats given C. butyricum showed decreased ALT, AST, LPS, and MDA; improved GSH and histological damage; changes in SCFAs; declined TNF-α, IL-6, TLR4, and pNF-κBp65/NF-κBp65; and changes in the gut microbial composition, which decreased the Firmicutes/Bacteroidetes ratio and increased the relative abundance (RA) of probiotics. Conclusions: C. butyricum supplementation protected against HIRI by regulating gut microbial composition, which contributed to the decreased LPS and attenuation of inflammation and oxidative stress. These indicate C. butyricum may be a potent clinical preoperative dietary supplement for HIRI.

Type C botulism in dogs from rural properties located in Goiânia, Brazil

Botulism is a disease usually fatal, caused by the ingestion of neurotoxins produced by Clostridium botulinum. In dogs, intoxication is caused by the ingestion of botulinum toxin type C, and animals often recover spontaneously. The present study describes the occurrence of type C botulism in two dogs domiciled on neighboring rural properties in the municipality of Goiânia, state of Goiás, Brazil, probably associated with ingestion of decomposing bovine carcass. Upon clinical evaluation, the dogs were alert in the lateral decubitus position with ascending flaccid paralysis, absence of eyelid reflexes, and reduced muscle tone. Due to their worsening clinical symptoms, the animals died within 12 h and 3 days after supportive treatment. Botulinum toxin type C was identified, in the serum and feces of both dogs, by seroneutralization in mice with homologous monovalent antitoxin. The results of the high-throughput gene sequencing showed that the abundance of C. botulinum in the fecal microbiota of one of the affected dogs was low (0.53%). In this way, the present study highlights the need of sanitary practices related to the appropriate collection and disposal of bovine carcasses in rural areas since they represent a risk factor for the occurrence of botulism in dogs domiciled on rural properties.