Association of Fidaxomicin with C. difficile spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production.

Background: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production. Methods: Prevalent UK C. difficile ribotypes (n=10) were incubated with 200mg/L fidaxomicin, vancomycin or a non-antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay. Results: Fidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean=10.1mg/L; range= 4.0-14mg/L) and faecal filtrate (mean =17.4mg/L; 8.4-22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples. Conclusion: Fidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates

From Eshu to Obatala: animals used in sacrificial rituals at Candomblé "terreiros" in Brazil

<p>Abstract</p> <p>Background</p> <p>The practice of sacrifice has occurred in several cultures and religions throughout history and still exists today. Candomblé, a syncretical Afro-Brazilian religion, practices the sacrificial ritual called "<it>Orô</it>" by its adherents. The present work aims to document the use of animal species in these sacrificial practices in the cities of Caruaru (PE) and Campina Grande (PB) in Norteastern Brazil, and to further understand the symbolism of these rituals.</p> <p>Methods</p> <p>Semi-structured and unstructured interviews and informal discussions were held with 11 Candomblé priests and priestesses between the months of August 2007 and June 2008. We attended rituals performed at "terreiros" where animals were sacrificed, in order to obtain photographic material and observe the procedures and techniques adopted.</p> <p>Results</p> <p>A total of 29 animal species were used during sacrificial rituals according to the priests and priestesses. These species were classified in 5 taxanomic groups: Molluscs (n = 1), Amphibians (n = 2), Reptiles (n = 2), Birds (n = 10) and Mammals (n = 14). According to Candomblé beliefs, animals are sacrificed and offered to their deities, known as orishas, for the prosperity of all life. There is a relationship between the colour, sex and behaviour of the animal to be sacrificed, and the orisha to whom the animal is going to be offered. The many myths that form the cosmogony of Candomblé can often explain the symbolism of the rituals observed and the animal species sacrificed. These myths are conveyed to adherants by the priests and priestesses during the ceremonies, and are essential to the continuation of this religion.</p> <p>Conclusion</p> <p>Candomblé is a sacrificial religion that uses animals for its liturgical purposes. The principal reason for sacrifice is to please supernatural deities known as orishas in order to keep life in harmony. This is accomplished through feeding them in a spiritual sense through sacrifice, maintaining a perfect link between men and the gods, and a connection between the material world (called <it>Aiyê</it>) and the supernatural world (called <it>Orun</it>).</p

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe