BackgroundOn 29 January 2024, the European Centre for Disease Prevention and Control distributed an alert about a metronidazole-resistant Clostridioides difficile outbreak of PCR ribotype (RT) 955 in England.AimWe aimed to investigate the presence of RT955 in Czech, Slovak and Polish C. difficile isolates and evaluate different culture media for detecting its metronidazole resistance.MethodsIsolates with binary toxin genes identified as 'unknown' by the WEBRIBO PCR ribotyping database up to 2023 were re-analysed after adding the RT955 profile to the database. The RT955 isolates were characterised by whole genome sequencing and tested for susceptibility to 15 antimicrobials.ResultsWe did not find RT955 in Czech (n = 6,661, 2012-2023) and Slovak (n = 776, 2015-2023) isolates, but identified 13 RT955 cases (n = 303, 2021-2023) in three hospitals in Poland. By whole genome multilocus sequence typing, 10 isolates clustered into one clonal complex including a sequence of United Kingdom strain ERR12670107, and shared similar antimicrobial resistance genes/mutations. All 13 isolates were resistant to ciprofloxacin/moxifloxacin, erythromycin/clindamycin and ceftazidime. All isolates had a mutation in the nimB gene promoter and in NimB (Tyr130Ser and Leu155Ile). The metronidazole resistance was detected in all isolates using brain-heart-infusion agar supplemented with haemin and Chocolate agar. Results were discrepant with the European Committee on Antimicrobial Susceptibility Testing-recommended Fastidious anaerobe agar and Brucella blood agar.ConclusionThe identification of clonally related haem-dependent metronidazole-resistant C. difficile RT955 in multiple hospitals indicates a need for prospective surveillance to estimate its prevalence in Europe.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální léková rezistence * genetika MeSH
- Clostridioides difficile * genetika účinky léků izolace a purifikace klasifikace MeSH
- epidemický výskyt choroby MeSH
- klostridiové infekce * epidemiologie mikrobiologie farmakoterapie MeSH
- lidé MeSH
- metronidazol * farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- polymerázová řetězová reakce MeSH
- ribotypizace * MeSH
- sekvenování celého genomu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Polsko MeSH
- Slovenská republika MeSH
OBJECTIVES: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short-,intermediate-, and long-term post-discharge complications among these patients. METHODS: A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-month post-discharge IBD-related complication rates defined as steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6 month and mortality at 12 month among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. RESULTS: In a cohort of 654 patients hospitalized for IBD {age 68.9 (interquartile range [IQR]): 63.9-75.2 years, 60.9% ulcerative colitis (UC)}, 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6 months, and 12 months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs 33.1%, p = 0.8; 40.5% vs 42.5%, p = 0.66; and 4.6% vs 8%, p = 0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3 months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An UC diagnosis was the sole risk factor for complication at 6 months (aOR 1.5). Clostridioides difficile infection did not significantly impact outcomes or interact with IBD type. CONCLUSIONS: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1 year.
- MeSH
- Clostridioides difficile MeSH
- hospitalizace statistika a číselné údaje MeSH
- idiopatické střevní záněty * komplikace MeSH
- klostridiové infekce * komplikace epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- propuštění pacienta MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- syndrom vzplanutí nemoci MeSH
- znovupřijetí pacienta statistika a číselné údaje MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVES: To analyse characteristics of Clostridioides difficile PCR ribotype 176 clinical isolates from Poland, the Czech Republic and Slovakia with regard to the differences in its epidemiology. METHODS: Antimicrobial susceptibility testing and whole genome sequencing were performed on a selected group of 22 clonally related isolates as determined by multilocus variable-number tandem repeat analysis (n = 509). Heterologous expression and functional analysis of the newly identified methyltransferase were performed. RESULTS: Core genome multilocus sequence typing found 10-37 allele differences. All isolates were resistant to fluoroquinolones (gyrA_p. T82I), aminoglycosides with aac(6')-Ie-aph(2'')-Ia in six isolates. Erythromycin resistance was detected in 21/22 isolates and 15 were also resistant to clindamycin with ermB gene. Fourteen isolates were resistant to rifampicin with rpoB_p. R505K or p. R505K/H502N, and five to imipenem with pbp1_p. P491L and pbp3_p. N537K. PnimBG together with nimB_p. L155I were detected in all isolates but only five were resistant to metronidazole on chocolate agar. The cfrE, vanZ1 and cat-like genes were not associated with linezolid, teicoplanin and chloramphenicol resistance, respectively. The genome comparison identified six transposons carrying antimicrobial resistance genes. The ermB gene was carried by new Tn7808, Tn6189 and Tn6218-like. The aac(6')-Ie-aph(2'')-Ia were carried by Tn6218-like and new Tn7806 together with cfrE gene. New Tn7807 carried a cat-like gene. Tn6110 and new Tn7806 contained an RlmN-type 23S rRNA methyltransferase, designated MrmA, associated with high-level macrolide resistance in isolates without ermB gene. CONCLUSIONS: Multidrug-resistant C. difficile PCR ribotype 176 isolates carry already described and unique transposons. A novel mechanism for erythromycin resistance in C. difficile was identified.
- MeSH
- antibakteriální látky * farmakologie MeSH
- bakteriální léková rezistence * MeSH
- bakteriální proteiny genetika MeSH
- Clostridioides difficile * genetika účinky léků izolace a purifikace klasifikace MeSH
- genomové ostrovy * MeSH
- klostridiové infekce * mikrobiologie epidemiologie MeSH
- lidé MeSH
- methyltransferasy genetika MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence * genetika MeSH
- multilokusová sekvenční typizace MeSH
- ribotypizace MeSH
- sekvenování celého genomu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Polsko MeSH
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
OBJECTIVES: To assess the effectiveness of shortened regimens of vancomycin or fidaxomicin in the treatment of Clostridioides difficile infection (CDI). METHODS: Adult patients with CDI hospitalized from January 2022 to May 2023 were included in this observational study. In patients with CDI treated with vancomycin or fidaxomicin, antibiotic treatment was discontinued after either 5 or 7 days of vancomycin or 5 days of fidaxomicin if there was a clinical response and improvement in laboratory parameters. The control cohort was treated with the standard 10 day regimen of either vancomycin or fidaxomicin. The follow-up was 60 days. Causative C. difficile strains were characterized by ribotyping and toxin gene detection when available. RESULTS: Twenty-five patients (median age 76 years) received shortened treatment with vancomycin (n = 21), or fidaxomicin (n = 4). Five cases fulfilled the criteria for severe CDI. Twenty-three patients completed follow-up; two died from causes other than CDI, and two developed recurrent CDI (8.0%). Ribotypes (RTs) 001 and 014 were the most prevalent with 20% each. In two C. difficile isolates, binary toxin genes were detected (RTs 078 and 023). In the control group of 22 patients recurrent CDI developed in 5 patients (22.7%). No statistically significant differences were found between the groups. CONCLUSIONS: Shortened treatment regimens for CDI with vancomycin and fidaxomicin were shown to be effective in our cohort of patients compared with 10 days of treatment. The recurrence rate was lower in the study group. A larger, prospective, double-blind, randomized, multicentre study is needed to support our findings.
- MeSH
- antibakteriální látky * terapeutické užití aplikace a dávkování MeSH
- Clostridioides difficile * genetika účinky léků klasifikace MeSH
- fidaxomicin * terapeutické užití aplikace a dávkování MeSH
- klostridiové infekce * farmakoterapie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- ribotypizace * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vankomycin * terapeutické užití aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie 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.
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
