BACKGROUND: Faecal microbiota transplantation (FMT) is the standard treatment for patients with multiple recurrent Clostridioides difficile infection (rCDI). Recently, new commercially developed human microbiota-derived medicinal products have been evaluated and Food and Drug Administration-approved with considerable differences in terms of composition, administration, and targeted populations. OBJECTIVES: To review available data on the different microbiota-derived treatments at the stage of advanced clinical evaluation and research in rCDI in comparison with FMT. SOURCES: Phase II or III trials evaluating a microbiota-derived medicinal product to prevent rCDI. CONTENT: Two commercial microbiota-derived medicinal products are approved by the Food and Drug Administration: Rebyota (RBX2660 Ferring Pharmaceuticals, marketed in the United States) and VOWST (SER-109 -Seres Therapeutics, marketed in the United States), whereas VE303 (Vedanta Biosciences Inc) will be studied in phase III trial. RBX2660 and SER-109 are based on the processing of stools from healthy donors, whereas VE303 consists of a defined bacterial consortium originating from human stools and produced from clonal cell banks. All have proven efficacy to prevent rCDI compared with placebo in patients considered at high risk of recurrence. However, the heterogeneity of the inclusion criteria, and the time between each episode and CDI diagnostics makes direct comparison between trials difficult. The differences regarding the risk of recurrence between the treatment and placebo arms were lower than previously described for FMT (FMT: Δ = 50.5%; RBX2660-phase III: Δ = 13.1%; SER-109-phase III: Δ = 28%; high-dose VE303-phase-II: Δ = 31.7%). All treatments presented a good overall safety profile with mainly mild gastrointestinal symptoms. IMPLICATIONS: Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI.
- MeSH
- Clostridioides difficile * MeSH
- fekální transplantace MeSH
- klostridiové infekce * mikrobiologie MeSH
- lidé MeSH
- mikrobiota * MeSH
- recidiva MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Clostridioides difficile is a leading cause of healthcare-associated infections. The main objective was to assess the current landscape of CDI infection prevention and control (IPC) practices. An anonymous survey of IPC practices for CDI was conducted between July 25 and October 31, 2022. Precautions for symptomatic patients were applicable for 75.9% and were discontinued 48 h minimum after the resolution of diarrhea for 40.7% of respondents. Daily cleaning of CDI patients' rooms was reported by 23 (42.6%). There was unexpected heterogeneity in IPC practices regarding the hospital management of CDI.
The ribotyping of Clostridioides difficile is one of the basic methods of molecular epidemiology for monitoring the spread of C. difficile infections. In the Czech Republic, this procedure is mainly available in university hospitals. The introduction of ribotyping in a tertiary health care facility such as Liberec Regional Hospital not only increases safety in the facility but also supports regional professional development. In our study, 556 stool samples collected between June 2017 and June 2018 were used for C. difficile infection screening, followed by cultivation, toxinotyping, and ribotyping of positive samples. The toxinotyping of 96 samples revealed that 44.8% of typed strains could produce toxins A and B encoded by tcdA and tcdB, respectively. The ribotyping of the same samples revealed two epidemic peaks, caused by the regionally most prevalent ribotype 176 (n = 30, 31.3). C. difficile infection incidence ranged between 5.5 and 4.2 cases per 10,000 patient-bed days. Molecular diagnostics and molecular epidemiology are the two most developing parts of clinical laboratories. The correct applications of molecular methods help ensure greater safety in hospitals.
BACKGROUND: Only a few studies dealt with the occurrence of endospore-forming clostridia in the microbiota of infants without obvious health complications. METHODS: A methodology pipeline was developed to determine the occurrence of endospore formers in infant feces. Twenty-four fecal samples (FS) were collected from one infant in monthly intervals and were subjected to variable chemical and heat treatment in combination with culture-dependent analysis. Isolates were identified by MALDI-TOF mass spectrometry, 16S rRNA gene sequencing, and characterized with biochemical assays. RESULTS: More than 800 isolates were obtained, and a total of 21 Eubacteriales taxa belonging to the Clostridiaceae, Lachnospiraceae, Oscillospiraceae, and Peptostreptococcaceae families were detected. Clostridium perfringens, C. paraputrificum, C. tertium, C. symbiosum, C. butyricum, and C. ramosum were the most frequently identified species compared to the rarely detected Enterocloster bolteae, C. baratii, and C. jeddahense. Furthermore, the methodology enabled the subsequent cultivation of less frequently detectable gut taxa such as Flavonifractor plautii, Intestinibacter bartlettii, Eisenbergiella tayi, and Eubacterium tenue. The isolates showed phenotypic variability regarding enzymatic activity, fermentation profiles, and butyrate production. CONCLUSIONS: Taken together, this approach suggests and challenges a cultivation-based pipeline that allows the investigation of the population of endospore formers in complex ecosystems such as the human gastrointestinal tract.
- MeSH
- Clostridium * genetika MeSH
- feces mikrobiologie MeSH
- Firmicutes genetika MeSH
- kojenec MeSH
- lidé MeSH
- mikrobiota * MeSH
- RNA ribozomální 16S genetika MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Environmental microorganisms usually exhibit a high level of genomic plasticity and metabolic versatility that allow them to be well-adapted to diverse environmental challenges. This study used shotgun metagenomics to decipher the functional and metabolic attributes of an uncultured Paracoccus recovered from a polluted soil metagenome and determine whether the detected attributes are influenced by the nature of the polluted soil. Functional and metabolic attributes of the uncultured Paracoccus were elucidated via functional annotation of the open reading frames (ORFs) of its contig. Functional tools deployed for the analysis include KEGG, KEGG KofamKOALA, Clusters of Orthologous Groups of proteins (COG), Comprehensive Antibiotic Resistance Database (CARD), and the Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT V6) for antibiotic resistance genes, TnCentral for transposable element, Transporter Classification Database (TCDB) for transporter genes, and FunRich for gene enrichment analysis. Analyses revealed the preponderance of ABC transporter genes responsible for the transport of oligosaccharides (malK, msmX, msmK, lacK, smoK, aglK, togA, thuK, treV, msiK), monosaccharides (glcV, malK, rbsC, rbsA, araG, ytfR, mglA), amino acids (thiQ, ynjD, thiZ, glnQ, gluA, gltL, peb1C, artP, aotP, bgtA, artQ, artR), and several others. Also detected are transporter genes for inorganic/organic nutrients like phosphate/phosphonate, nitrate/nitrite/cyanate, sulfate/sulfonate, bicarbonate, and heavy metals such as nickel/cobalt, molybdate/tungstate, and iron, among others. Antibiotic resistance genes that mediate efflux, inactivation, and target protection were detected, while transposable elements carrying resistance phenotypes for antibiotics and heavy metals were also annotated. The findings from this study have established the resilience, adaptability, and survivability of the uncultured Paracoccus in the hydrocarbon-polluted soil.
- MeSH
- ABC transportéry genetika MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální toxiny * MeSH
- Clostridioides difficile * genetika MeSH
- metagenom MeSH
- Paracoccus * genetika MeSH
- půda chemie MeSH
- těžké kovy * MeSH
- transpozibilní elementy DNA MeSH
- uhlovodíky MeSH
- Publikační typ
- časopisecké články MeSH
Klostrídiová kolitída bola dlhodobo považovaná za infekciu asociovanú s hospitalizáciou a súčasnou antibiotickou liečbou. Narastajúci počet prípadov v komunite však v posledných rokoch viedol k prehodnoteniu tradičného chápania jej epidemiologických charakteristík. Komunitné formy boli navyše mnohokrát zaznamenané u detí, mladých dospelých či ľudí bez komorbidít a s negatívnou anamnézou užívania antibiotík v predchorobí. Uvedené skupiny boli tradične považované za nízkorizikové pre vznik ochorenia. Mnohé štúdie tak prirodzene skúmali vplyv asymptomatických prenášačov Clostridioides difficile, vrátane novorodencov a dojčiat, na prenos pôvodcu ochorenia v komunite. Predmetom výskumu sa stal aj výskyt tejto baktérie u zvierat, v potrave a environmentálnom prostredí. Snahou bolo ozrejmiť úlohu uvedených faktorov v šírení pôvodcu v komunitných podmienkach. V článku sumarizujeme aktuálne poznatky o potvrdených a potencionálnych rizikových faktoroch komunitnej formy klostrídiovej kolitídy, spoločne s výsledkami štúdií skúmajúcich charakteristiky týchto pacientov. Zároveň prinášame informácie o problematike výskytu klostrídiovej kolitídy v detskej populácii, ktorá je s komunitnou formou infekcie úzko previazaná.
Clostridioides difficile colitis has long been considered an infection associated with hospitalization and concomitant antibiotic treatment. However, the increasing number of community cases in recent years has led to a reassessment of the traditional understanding of its epidemiological characteristics. In addition, community-associated forms have been reported many times in children, young adults, or people without comorbidities and with a negative history of antibiotic use in the pre-disease period. These groups have traditionally been considered low risk for the development of the infection. Thus, many studies have naturally investigated the impact of asymptomatic Clostridioides difficile carriers, including neonates and infants, on the transmission of the causative agent in the community. The prevalence of this bacterium in animals, in food and in the environmental setting has also been the subject of research. The goal was to elucidate the role of these factors in the spread of the agent in community settings. In this article, we summarize the current knowledge on confirmed and potential risk factors for community-acquired Clostridioides difficile infection, together with the results of studies examining patient characteristics. We also provide information on the issue of Clostridioides difficile infection in the paediatric population, which is closely intertwined with the community-acquired form of the infection.
Problematika střevní dysbiózy je v současnosti předmětem intenzivního výzkumu, alterace mikrobioty je dávána do souvislosti s patogenezí řady chorobných stavů. Určitým prototypem nemoci, u které hraje narušení přirozené rovnováhy mikrobiálního ekosystému střeva klíčovou roli, je rekurentní klostridiová kolitida. Velmi nadějnou metodou mající potenciál terapeuticky zasáhnout právě na úrovni alterované intestinální mikrobioty je fekální bakterioterapie. Jedná se dnes již o globálně plně etablovanou metodu, která má za cíl dosáhnout obnovy přirozené mikrobiální homeostázy ve střevě pomocí stolice od zdravého dárce, která je přenesena do střeva pacienta. Obnovením kolonizační rezistence tlustého střeva dokáže transplantace střevní mikrobioty prolomit pomyslný bludný kruh opakovaných atak klostridiové kolitidy. V rámci sekundární profylaxe rekurentní klostridiové kolitidy je fekální bakterioterapie metodou velmi efektivní, bezpečnou a pacienty dobře tolerovanou. Její budoucnost vidíme jednak ve zdokonalování způsobu podání fekálního transplantátu (včetně enterosolventních kapslí), jednak v cílenější manipulaci s intestinální mikrobiotou, což povede k rozšíření indikací o řadu dalších onemocnění.
The problematic of intestinal dysbiosis is currently an object of intensive research, alteration of microbiota is related to pathogenesis of a whole array of disease states. A certain prototype of illness at which disruption of natural balance of intestinal microbial ecosystem plays a key role is recurrent Clostridium difficile colitis. A very hopeful method having the potential to therapeutically intervene exactly at the level of altered intestinal microbiota is fecal bacteriotherapy. It is already globally established method with aim to achieve the restoration of natural microbial homeostasis in the intestine using stool of healthy donor which is transplanted into the intestines of a patient. By restoring the colonization resistance of large intestine, the transplantation of intestinal microbiota can break an imaginary vicious cycle of repeated attacks of Clostridium difficile colitis. Within secondary prophylaxis of recurrent Clostridium difficile colitis, fecal bacteriotherapy is a very effective, safe, and by patients well-tolerated method. We can see its future in both improvement of the fecal transplant administration method (including enteric capsules) and more targeted manipulation with intestinal microbiota which will lead to extension of indications by an array of other illnesses.
- Klíčová slova
- intestinální dysbióza,
- MeSH
- Clostridioides difficile MeSH
- dysbióza terapie MeSH
- fekální transplantace * metody MeSH
- klostridiové infekce terapie MeSH
- lidé MeSH
- pseudomembranózní enterokolitida * terapie MeSH
- střevní mikroflóra MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
A total of, 78 Clostridium septicum (CLSE) isolates were screened for genes encoding: α-toxin, flagellin, and resistance to vancomycin (VANg). The isolates were also tested for their ability to form biofilm and their antibiotic susceptibility. All isolates were positive for α-toxin and flagellin genes. However, only 19 isolates (24.3%) showed prevalence for VANg. We observed the strongest capacity to form a biofilm (100%) in isolates from patients with oncologic or septic and febrile diagnoses. This percentage was also very high in patients with colitis and gastrointestinal hemorrhage (72.7%). No less than 43 isolates showed antibiotic resistance, and 21 were multidrug-resistant (MDR). Interestingly, our studies showed a correlation between antibiotic resistance and biofilm formation. A statistically significant difference was observed between biofilm-forming MDR isolates and those with low/no biofilm-forming ability. However, the most impressive observation was the correlation with mortality rate. While the overall mortality rate for CLSE infections was 16.7% (13/78), the mortality rate for patients infected with MDR isolates forming biofilm moderately or strongly reached 38.1% (8/21). This number increased even further when only infections with the biofilm-forming VANg-positive isolates were considered (61.5%; 8/13). Therefore, the ability of a VANg-positive CLSE isolate to form a biofilm has been suggested as a biomarker of poor prognosis.
AIM: To investigate the epidemiology of Clostridioides difficile infection (CDI) in Slovakian hospitals after the emergence of ribotype 176 (027-like) in 2016. METHODS: Between 2018 and 2019, European Centre for Disease Control and Prevention CDI surveillance protocol v2.3 was applied to 14 hospitals, with additional data collected on recent antimicrobial use and the characterization of C. difficile isolates. RESULTS: The mean hospital incidence of CDI was 4.1 cases per 10,000 patient bed-days. One hundred and five (27.6%) in-hospital deaths were reported among the 381 cases. Antimicrobial treatment within the previous 4 weeks was recorded in 90.5% (333/368) of cases. Ribotype (RT)176 was detected in 50% (n=185/370, 14 hospitals) and RT001 was detected in 34.6% (n=128/370,13/14 hospitals) of cases with RT data. Overall, 86% (n=318/370) of isolates were resistant to moxifloxacin by Thr82Ile in GyrA (99.7%). Multi-locus variable tandem repeat analysis showed clonal relatedness of predominant RTs within and between hospitals. Seven of 14 sequenced RT176 isolates and five of 13 RT001 isolates showed between zero and three allelic differences by whole-genome multi-locus sequence typing. The majority of sequenced isolates (24/27) carried the erm(B) gene and 16/27 also carried the aac(6')-aph(2'') gene with the corresponding antimicrobial susceptibility phenotypes. Nine RT176 strains carried the cfr(E)gene and one RT001 strain carried the cfr(C) gene, but without linezolid resistance. CONCLUSIONS: The newly-predominant RT176 and endemic RT001 are driving the epidemiology of CDI in Slovakia. In addition to fluoroquinolones, the use of macrolide-lincosamide-streptogramin B antibiotics can represent another driving force for the spread of these epidemic lineages. In C. difficile, linezolid resistance should be confirmed phenotypically in strains with detected cfr gene(s).
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- Clostridioides difficile * genetika MeSH
- Clostridioides genetika MeSH
- fluorochinolony farmakologie MeSH
- klostridiové infekce * epidemiologie farmakoterapie MeSH
- lidé MeSH
- linezolid MeSH
- makrolidy MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- ribotypizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- Clostridioides difficile * MeSH
- fekální transplantace MeSH
- klostridiové infekce * terapie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
