Our aim was to study Clostridium difficile infection (CDI) in peripartum women in France and compare them to cases published in the literature. We characterize these infections regarding clinico-biological features and specific risk factors in order to raise awareness for obstetricians and midwifes. Eight antepartum and six post-partum CDI cases were retrospectively studied in 6 French centers during the period between 2008 and 2013. In addition, 59 literature cases were reviewed. Cases were identified with CDI clinical symptoms associated to characteristic imagery or detection of C. difficile toxins. The key risk factors of CDI (antibiotherapy, hospitalization) and other risk factors (cesarean section, obstetric complications, corticotherapy, and underlying disease) were retrospectively collected. Most of the cases were exposed to at least one key risk factor of CDI: previous exposure to antibiotics and/or hospitalization. The post-partum cases often had cesarean section: 67% (4/6) in French cases and 89% (31/35) in literature cases. Metronidazole was the most used antibiotic. Relapses occurred in two French cases and in nine published cases. Two French cases and 15 literature cases were reported to have complications (pseudomembranous colitis, toxic megacolon, death…). Diverse C. difficile PCR ribotypes were involved, but the BI/NAP1/027 strain was not detected in the French case series contrary to the literature cases. The delay for diagnosis CDI could be long and peripartum CDI could be severe. In case of unexplained diarrhea in pregnant women, clinicians need to consider CDI and ask for research of C. difficile and its toxins in stool.

Clostridium difficile is a major cause of hospital-associated diarrhoea, and in severe cases leads to pseudomembranous colitis and toxic megacolon. The frequency of C. difficile infection (CDI) has increased in recent decades, with 453 000 cases identified in 2011 in the USA. This is related to antibiotic-selection pressure, disruption of normal host intestinal microbiota and emergence of antibiotic-resistant C. difficile strains. The burden of community-acquired CDI has been increasingly appreciated, with disease identified in patients previously considered low-risk, such as young women or patients with no prior antibiotic exposure. C. difficile has been identified in livestock animals, meat products, seafood and salads. It has been postulated that the pool of C. difficile in the agricultural industry may contribute to human CDI. There is widespread environmental dispersal of C. difficile spores. Domestic households, turf lawns and public spaces are extensively contaminated, providing a potential reservoir for community-acquired CDI. In Australia, this is particularly associated with porcine-derived C. difficile UK PCR ribotype 014/020. In this article, the epidemiological differences between hospital- and community-acquired CDI are discussed, including some emerging evidence for community-acquired CDI being a possible zoonosis.

Clostridium difficile is a spore forming bacterium and the leading cause of colitis and antibiotic associated diarrhoea in the developed world. Effective recovery of spores, particularly in low numbers, is imperative to obtain accurate prevalence data, due to the low number of spores found within non-clinical samples (<20/ml). Through comparison of C. difficile enrichment media, this study showed the importance of selecting an effective enrichment media. Commonly used broths, such as Cooked Meat broth, promote significantly less growth than other available broths such as Brain Heart Infusion broth, BHI. The optimization of BHI using selective antibiotics, moxalactam and norfloxacin, and sodium taurocholate at a concentration of 0.4%, allowed for high growth rate (0.465 hour-1), short lag times (<14 hours) and recovery of spores at low concentrations. The optimized broth, designated BHIMN-T, out-performed other commonly used broths so can be recommended for future studies.

Clostridium difficile infection (CDI) continues to possess a significant disease burden in the United States (US) as well as all over the world. Given the increase in severity and recurrence rate, the decrease in cure rate, and the fact that the virulent ribotype 027 strain remains one of the most commonly identified strains in the US, the Infectious Diseases Society of America (IDSA) published a clinical practice guideline in February 2018 moving away from metronidazole as the first-line treatment for initial CDI and recommending either oral vancomycin or fidaxomicin. The aim of this study is to evaluate the clinical data available comparing the efficacy of primary treatment of CDI between those two antibiotics. We performed a PubMed, PubMed Central, and ScienceDirect database search without restriction to regions, publication types, or languages. A comprehensive literature search was performed from January 1, 1980 up to March 20, 2018. We used the following keywords in different combinations: Clostridium difficile, Clostridium difficile infection, CDI, C. diff, C. difficile, fidaxomicin, vancomycin, pseudomembranous colitis, and antibiotic-associated colitis. The search was limited to human studies. Data were independently extracted by two reviewers with disagreements resolved by a third author. We pooled an odds ratio (OR) on two primary outcomes: Clinical cure rate and rate of recurrence during the follow-up period. The computer search was also supplemented with manual searches by the authors of the retrieved review articles and primary studies. The search phrase "((Clostridium difficile) AND vancomycin) AND fidaxomicin" had the highest yield results. We identified four observational studies with a total of 2,303 patients with CDI that met our inclusion criteria. Compared with vancomycin, fidaxomicin use was associated with a significantly lower recurrence of CDI with a pooled OR of 0.47 (95% confidence interval (CI), 0.37 - 0.60, I2 = 0). On the other hand, there was no significant association of fidaxomicin use with CDI cure rate compared to vancomycin with a pooled OR of 1.22 (95% CI, 0.93 - 1.60, I2 = 0). In light of the recently updated clinical practice guidelines by the IDSA, our review suggests that fidaxomicin has a more sustained clinical response with a statistically significant lower recurrence rate. Although fidaxomicin appears to be the better drug with statistical significance, its cost-effectiveness continues to be an ongoing controversy. More randomized clinical trials are needed to shed light on this matter to assess if there is any clinical significance in fidaxomicin superiority.

Clostridium difficile is recognized as a problematic pathogen, causing severe enteric diseases including antibiotic-associated diarrhea and pseudomembranous colitis. The emergence of antibiotic resistant C. difficile has driven a search for alternative anti-infection modalities. A promising strategy for controlling bacterial infection includes the use of bacteriophages and their gene products. Currently, knowledge of phages active against C. difficile is still relatively limited by the fact that the isolation of phages for this organism is a technically demanding method since bacterial host themselves are difficult to culture. To isolate and characterize phages specific to C. difficile, a genotoxic agent, mitomycin C, was used to induce temperate phages from 12 clinical isolates of C. difficile. Five temperate phages consisting of ΦHR24, ΦHN10, ΦHN16-1, ΦHN16-2, and ΦHN50 were successfully induced and isolated. Spotting assays were performed against a panel of 92 C. difficile isolates to screen for susceptible bacterial hosts. The results revealed that all the C. difficile phages obtained in this work displayed a relatively narrow host range of 0-6.5% of the tested isolates. Electron microscopic characterization revealed that all isolated phages contained an icosahedral head connected to a long contractile tail, suggesting that they belonged to the Myoviridae family. Restriction enzyme analysis indicated that these phages possess unique double-stranded DNA genome. Further electron microscopic characterization revealed that the ΦHN10 absorbed to the bacterial surface via attachment to cell wall, potentially interacting with S-layer protein. Bacteriophages isolated from this study could lead to development of novel therapeutic agents and detection strategies for C. difficile.

Clostridium difficile is a Gram-positive spore-former bacterium and the leading cause of nosocomial antibiotic-associated diarrhea that can culminate in fatal colitis. During the infection, C. difficile produces metabolically dormant spores, which persist in the host and can cause recurrence of the infection. The surface of C. difficile spores seems to be the key in spore-host interactions and persistence. The proteome of the outermost exosporium layer of C. difficile spores has been determined, identifying two cysteine-rich exosporium proteins, CdeC and CdeM. In this work, we explore the contribution of both cysteine-rich proteins in exosporium integrity, spore biology and pathogenesis. Using targeted mutagenesis coupled with transmission electron microscopy we demonstrate that both cysteine rich proteins, CdeC and CdeM, are morphogenetic factors of the exosporium layer of C. difficile spores. Notably, cdeC, but not cdeM spores, exhibited defective spore coat, and were more sensitive to ethanol, heat and phagocytic cells. In a healthy colonic mucosa (mouse ileal loop assay), cdeC and cdeM spore adherence was lower than that of wild-type spores; while in a mouse model of recurrence of the disease, cdeC mutant exhibited an increased infection and persistence during recurrence. In a competitive infection mouse model, cdeC mutant had increased fitness over wild-type. Through complementation analysis with FLAG fusion of known exosporium and coat proteins, we demonstrate that CdeC and CdeM are required for the recruitment of several exosporium proteins to the surface of C. difficile spores. CdeC appears to be conserved exclusively in related Peptostreptococcaeace family members, while CdeM is unique to C. difficile. Our results sheds light on how CdeC and CdeM affect the biology of C. difficile spores and the assembly of the exosporium layer and, demonstrate that CdeC affect C. difficile pathogenesis.