RESUMO
Type D enterotoxemia, caused by Clostridium perfringens epsilon toxin (ETX), is one of the most economically important clostridial diseases of sheep. Acute type D enterotoxemia is characterized by well-documented lesions in the nervous, cardiocirculatory, and pulmonary systems. However, discrepancies and confusion exist as to whether renal lesions are part of the spectrum of lesions of this condition, which is controversial considering that for many decades it has been colloquially referred to as "pulpy kidney disease." Here, the authors assess renal changes in an experimental model of acute type D enterotoxemia in sheep and evaluate the possible role of ETX in their genesis. Four groups of 6 sheep each were intraduodenally inoculated with either a wild-type virulent C. perfringens type D strain, an etx knockout mutant unable to produce ETX, the etx mutant strain complemented with the wild-type etx gene that regains the ETX toxin production, or sterile culture medium (control group). All sheep were autopsied less than 24 hours after inoculation; none of them developed gross lesions in the kidneys. Ten predefined histologic renal changes were scored in each sheep. The proportion of sheep with microscopic changes and their severity scores did not differ significantly between groups. Mild intratubular medullary hemorrhage was observed in only 2 of the 12 sheep inoculated with the wild-type or etx-complemented bacterial strains, but not in the 12 sheep of the other 2 groups. The authors conclude that no specific gross or histologic renal lesions are observed in sheep with experimental acute type D enterotoxemia.
Assuntos
Infecções por Clostridium , Doenças dos Ovinos , Ovinos , Animais , Clostridium perfringens/genética , Enterotoxemia/microbiologia , Infecções por Clostridium/patologia , Infecções por Clostridium/veterinária , Rim/patologia , Doenças dos Ovinos/patologiaRESUMO
Sarcina ventriculi is a gram-positive bacterium, able to survive in extreme low pH environment. It's first description dates from 1842, by John Goodsir. Since then, just a few cases have been reported. In veterinary medicine, especially in ruminants, it causes bloating, vomiting, gastric perforation and death of the animal. It is commonly associated with delayed gastric emptying or obstruction to gastric outlet, although it's pathogenicity in humans is not fully understood. We report two cases with identification of the bacteria in gastric specimens stained with hematoxylin-eosin staining, in different clinical settings. The first patient is a young female patient, presenting cardiac arrest and death after gastric perforation and the second patient an adult male presenting with gastric adenocarcinoma, treated with partial gastrectomy followed by adjuvant chemoradiation. In our literature review, we identified forty-five cases reporting Sarcina ventriculi appearance, with a sudden increase since 2010.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Pessoa de Meia-Idade , Sarcina/patogenicidade , Infecções por Clostridium/patologia , Gastroparesia/complicaçõesRESUMO
One of the main challenges associated with Clostridioides difficile infection (CDI) in humans and domestic animals is the lack of an effective preventive strategy. One strategy with promising results is the oral administration of non-toxigenic strains of C. difficile (NTCD). Recently, Z31, a NTCD strain isolated from a healthy dog, showed promising results to prevent CDI in hamsters. Thus, the present study aimed to evaluate the capacity of Z31 to prevent CDI in piglets using an experimental model. Twenty neonatal piglets were randomly distributed in three groups: G1 - 106 spores of Z31 followed by 107 spores of a toxigenic C. difficile strain (nâ¯=â¯7), G2 (positive control) - 107 spores of a toxigenic C. difficile strain (nâ¯=â¯7), and G3 (negative control) - no biological inoculum (nâ¯=â¯6). All animals were kept in individual insulators and observed for 60â¯h. Data regarding clinical signs, macro and microscopic lesions, toxigenic culture of C. difficile, and detection of A/B toxins in the feces were evaluated. All evaluated parameters were significantly lower in animals that received Z31 compared to the positive control. Thus, oral administration of Z31 was able to prevent CDI in piglets in an experimental model.
Assuntos
Antibiose , Terapia Biológica/métodos , Clostridiales/crescimento & desenvolvimento , Infecções por Clostridium/prevenção & controle , Administração Oral , Animais , Animais Recém-Nascidos , Toxinas Bacterianas/análise , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Modelos Animais de Doenças , Fezes/química , Suínos , Resultado do TratamentoRESUMO
AIM: To evaluate the effect on the nonsteroidal anti-inflammatory drug indomethacin on Clostridium difficile infection (CDI) severity. MATERIALS & METHODS: Indomethacin was administered in two different mouse models of antibiotic-associated CDI in two different facilities, using a low and high dose of indomethacin. RESULTS: Indomethacin administration caused weight loss, increased the signs of severe infection and worsened histopathological damage, leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed mice infected with C. difficile had enhanced intestinal inflammation with increased expression of KC, IL-1ß and IL-22 compared with infected mice unexposed to indomethacin. CONCLUSION: These results demonstrate a negative impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in mice and suggest that targeting the synthesis or signaling of prostaglandins might be an approach to ameliorating the severity of CDI.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Clostridioides difficile , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/patologia , Indometacina/efeitos adversos , Intestinos/patologia , Índice de Gravidade de Doença , Animais , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Modelos Animais de Doenças , Indometacina/administração & dosagem , Interleucina-1beta/metabolismo , Interleucinas/metabolismo , Intestinos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Antagonistas de Prostaglandina/efeitos adversos , Prostaglandinas/biossíntese , Fatores de Risco , Redução de Peso , Interleucina 22RESUMO
Clostridium difficile infection (CDI) are the leading cause of world-wide nosocomial acquired diarrhea. The current main clinical challenge in CDI is the elevated rate of infection recurrence that may reach up to 30% of the patients, which has been associated to the formation of dormant spores during the infection. We sought to characterize the effects of oral administration of specific anti-spore IgY in mouse models of CDI and recurrent CDI. The specificity of anti-spore IgY was evaluated in vitro. In both, initiation mouse model and recurrence mouse model, we evaluated the prophylactic and therapeutic effect of anti-spore IgY, respectively. Our results demonstrate that anti-spore IgY exhibited high specificity and titers against C. difficile spores and reduced spore adherence to intestinal cells in vitro. Administration of anti-spore IgY to C57BL/6 mice prior and during CDI delayed the appearance of the diarrhea by 1.5 day, and spore adherence to the colonic mucosa by 90%. Notably, in the recurrence model, co-administration of anti-spore IgY coupled with vancomycin delayed the appearance of recurrent diarrhea by a median of 2 days. Collectively, these observations suggest that anti-spore IgY antibodies may be used as a novel prophylactic treatment for CDI, or in combination with antibiotics to treat CDI and prevent recurrence of the infection.
Assuntos
Galinhas/imunologia , Clostridioides difficile/imunologia , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle , Imunoglobulinas/administração & dosagem , Imunoglobulinas/farmacologia , Imunoglobulinas/uso terapêutico , Esporos Bacterianos/imunologia , Adesinas Bacterianas/efeitos dos fármacos , Administração Oral , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/farmacologia , Anticorpos Antibacterianos/uso terapêutico , Proteínas de Bactérias/imunologia , Células CACO-2 , Infecções por Clostridium/patologia , Colo/microbiologia , Diarreia/tratamento farmacológico , Modelos Animais de Doenças , Combinação de Medicamentos , Fezes/microbiologia , Humanos , Imunização Passiva , Imunoglobulina G/sangue , Imunoglobulinas/isolamento & purificação , Imunoterapia , Intestinos/imunologia , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Vancomicina/farmacologiaRESUMO
One of the main clinical challenges of Clostridium difficile infections (CDI) is the high rate of relapse episodes. The main determinants involved in relapse of CDI include the presence of antibiotic-resistant C. difficile spores in the colonic environment and a permanent state of dysbiosis of the microbiota caused by antibiotic therapy. A possible scenario is that phenotypes related to the persistence of C. difficile spores might contribute to relapsing infections. In this study, 8 C. difficile isolates recovered from 4 cases with relapsing infection, and 9 isolates recovered from single infection cases were analyzed for PCR ribotyping and the presence of tcdA, tcdB and cdtAB genes. Factors associated to spore persistence, sporulation, spore adherence and biofilm formation and sporulation during biofilm formation were characterized. We also evaluated motility and cytotoxicity. However, we observed no significant difference in the analyzed phenotypes among the different clinical outcomes, most likely due to the high variability observed among strains within clinical backgrounds in each phenotype and the small sample size. It is noteworthy that C. difficile spores adhered to similar extents to undifferentiated and differentiated Caco-2 cells. By contrast, spores of all clinical isolates tested had increased germination efficiency in presence of taurocholate, while decreased sporulation rate during biofilm development in the presence of glucose. In conclusion, these results show that, at least in this cohort of patients, the described phenotypes are not detrimental in the clinical outcome of the disease.
Assuntos
Clostridioides difficile/patogenicidade , Infecções por Clostridium/microbiologia , Esporos Bacterianos/crescimento & desenvolvimento , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Células CACO-2 , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/fisiologia , Infecções por Clostridium/patologia , Estudos de Coortes , Farmacorresistência Bacteriana , Humanos , Fenótipo , Recidiva , Esporos Bacterianos/genética , Esporos Bacterianos/metabolismo , Esporos Bacterianos/patogenicidade , VirulênciaRESUMO
The prevalence of Clostridium difficile infections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This C. difficile variant elicited higher white blood cell counts and caused disease in younger patients than did other strains isolated during the outbreak. Furthermore, it had a recurrence rate, a 30-day attributable disease rate, and disease severity as great as those of the epidemic strain NAP1. Pulsed-field gel electrophoresis genotyping indicated that the outbreak strains belong to a previously undescribed variant, designated NAPCR1. Whole-genome sequencing and ribotyping indicated that the NAPCR1 variant belongs to C. difficile ribotype 012 and sequence type 54, as does the reference strain 630. NAPCR1 strains are resistant to fluoroquinolones due to a mutation in gyrA, and they possess an 18-bp deletion in tcdC that is characteristic of the epidemic, evolutionarily distinct, C. difficile NAP1 variant. NAPCR1 genomes contain 10% more predicted genes than strain 630, most of which are of hypothetical function and are present on phages and other mobile genetic elements. The increased virulence of NAPCR1 was confirmed by mortality rates in the hamster model and strong inflammatory responses induced by bacteria-free supernatants in the murine ligated loop model. However, NAPCR1 strains do not synthesize toxin A and toxin B at levels comparable to those in NAP1 strains. Our results suggest that the pathogenic potential of this emerging C. difficile variant is due to the acquisition of hypothetical functions associated with laterally acquired DNA.
Assuntos
Clostridioides difficile/isolamento & purificação , Clostridioides difficile/patogenicidade , Infecções por Clostridium/epidemiologia , Diarreia/epidemiologia , Surtos de Doenças , Animais , Clostridioides difficile/classificação , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Costa Rica/epidemiologia , Infecção Hospitalar/induzido quimicamente , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , DNA Bacteriano/genética , Diarreia/microbiologia , Diarreia/patologia , Modelos Animais de Doenças , Eletroforese em Gel de Campo Pulsado , Feminino , Transferência Genética Horizontal , Genótipo , Hospitais , Humanos , Intestinos/patologia , Masculino , Mesocricetus , Camundongos , Dados de Sequência Molecular , Tipagem Molecular , Estudos Retrospectivos , Ribotipagem , Análise de Sequência de DNA , Análise de Sobrevida , Virulência , Fatores de Virulência/genéticaRESUMO
Clostridium difficile is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis in healthcare settings. However, the host factors involved in the intestinal inflammatory response and pathogenesis of C. difficile infection (CDI) are largely unknown. Here we investigated the role of leukotrienes (LTs), a group of pro-inflammatory lipid mediators, in CDI. Notably, the neutrophil chemoattractant LTB4, but not cysteinyl (cys) LTs, was induced in the intestine of C57BL/6 mice infected with either C. difficile strain VPI 10463 or strain 630. Genetic or pharmacological ablation of LT production did not ameliorate C. difficile colitis or clinical signs of disease in infected mice. Histological analysis demonstrated that intestinal neutrophilic inflammation, edema and tissue damage in mice during acute and severe CDI were not modulated in the absence of LTs. In addition, CDI induced a burst of cytokines in the intestine of infected mice in a LT-independent manner. Serum levels of anti-toxin A immunoglobulin (Ig) G levels were also not modulated by endogenous LTs. Collectively, our results do not support a role for LTs in modulating host susceptibility to CDI in mice.
Assuntos
Clostridioides difficile/crescimento & desenvolvimento , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Colite/microbiologia , Colite/patologia , Leucotrienos/metabolismo , Animais , Clostridioides difficile/imunologia , Modelos Animais de Doenças , Feminino , Histocitoquímica , Camundongos Endogâmicos C57BLRESUMO
The objective of this study was to describe the first report involving a case of equine acute myonecrosis caused by C. novyi type A with an emphasis on clinical signs, the pathological and bacteriological analysis, and molecular identification of the microorganisms as the key of the definitive diagnosis.
Assuntos
Infecções por Clostridium/veterinária , Clostridium/classificação , Clostridium/isolamento & purificação , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/patologia , Miosite/veterinária , Necrose/veterinária , Animais , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Histocitoquímica , Doenças dos Cavalos/microbiologia , Cavalos , Miosite/diagnóstico , Miosite/microbiologia , Miosite/patologia , Necrose/diagnóstico , Necrose/microbiologia , Necrose/patologia , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
The objective of this study was to describe the first report involving a case of equine acute myonecrosis caused by C. novyi type A with an emphasis on clinical signs, the pathological and bacteriological analysis, and molecular identification of the microorganisms as the key of the definitive diagnosis.