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
- MeSH
- antibakteriální látky * terapeutické užití MeSH
- klostridiové infekce * farmakoterapie MeSH
- lidé MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy 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.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health care-associated infections. Additionally, over the decades, the spread of community-associated (CA-MRSA) clones has become a serious problem. The aim of this study was to gain data on the current epidemiology of MRSA in Slovakia. Between January 2020 and March 2020, single-patient MRSA isolates (invasive and/or colonizing) were collected in Slovakia from hospitalized inpatients (16 hospitals) or outpatients (77 cities). Isolates were characterized via antimicrobial susceptibility testing, spa typing, SCCmec typing, the detection of mecA/mecC, genes coding for Panton-Valentine leukocidin (PVL), and the arcA gene (part of the arginine catabolic mobile element [ACME]). Out of 412 isolates, 167 and 245 originated from hospitalized patients and outpatients, respectively. Inpatients were most likely older (P < 0.001) and carried a strain exhibiting multiple resistance (P = 0.015). Isolates were frequently resistant to erythromycin (n = 320), clindamycin (n = 268), and ciprofloxacin/norfloxacin (n = 261). 55 isolates were resistant to oxacillin/cefoxitin only. By clonal structure, CC5-MRSA-II (n = 106; spa types t003, t014), CC22-MRSA-IV (n = 75; t032), and CC8-MRSA-IV (n = 65; t008) were the most frequent. We identified PVL in 72 isolates (17.48%; 17/412), with the majority belonging to CC8-MRSA-IV (n = 55; arcA+; t008, t622; the USA300 CA-MRSA clone) and CC5-MRSA-IV (n = 13; t311, t323). To the best of our knowledge, this is the first study on the epidemiology of MRSA in Slovakia. The presence of the epidemic HA-MRSA clones CC5-MRSA-II and CC22-MRSA-IV was found, as was, importantly, the emergence of the global epidemic USA300 CA-MRSA clone. The extensive spread of USA300 among inpatients and outpatients across the Slovakian regions warrants further investigation. IMPORTANCE The epidemiology of MRSA is characterized by the rise and fall of epidemic clones. Understanding the spread, as well as the evolution of successful MRSA clones, depends on the knowledge of global MRSA epidemiology. However, basic knowledge about MRSA epidemiology is still fragmented or completely missing in some parts of the world. This is the first study of MRSA epidemiology in Slovakia to identify the presence of the epidemic HA-MRSA clones CC5-MRSA-II and CC22-MRSA-IV and, importantly and unexpectedly, the emergence of the global epidemic USA300 CA-MRSA clone in the Slovakian community and hospitals. So far, USA300 has failed to spread in Europe, and this study documents an extensive spread of this epidemic clone in a European country for the first time.
- MeSH
- infekce spojené se zdravotní péčí * epidemiologie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * genetika MeSH
- mikrobiální testy citlivosti MeSH
- nemocnice MeSH
- stafylokokové infekce * epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
INTRODUCTION: Hospitals and wastewater are recognized hot spots for the selection and dissemination of antibiotic-resistant bacteria to the environment, but the total participation of hospitals in the spread of nosocomial pathogens to municipal wastewater treatment plants (WWTPs) and adjacent rivers had not previously been revealed. METHODS: We used a combination of culturing and whole-genome sequencing to explore the transmission routes of Escherichia coli from hospitalized patients suffering from urinary tract infections (UTI) via wastewater to the environment. Samples were collected in two periods in three locations (A, B, and C) and cultured on selective antibiotic-enhanced plates. RESULTS: In total, 408 E. coli isolates were obtained from patients with UTI (n=81), raw hospital sewage (n=73), WWTPs inflow (n=96)/outflow (n=106), and river upstream (n=21)/downstream (n=31) of WWTPs. The majority of the isolates produced extended-spectrum beta-lactamase (ESBL), mainly CTX-M-15, and showed multidrug resistance (MDR) profiles. Seven carbapenemase-producing isolates with GES-5 or OXA-244 were obtained in two locations from wastewater and river samples. Isolates were assigned to 74 different sequence types (ST), with the predominance of ST131 (n=80) found in all sources including rivers. Extraintestinal pathogenic lineages frequently found in hospital sewage (ST10, ST38, and ST69) were also found in river water. Despite generally high genetic diversity, phylogenetic analysis of ST10, ST295, and ST744 showed highly related isolates (SNP 0-18) from different sources, providing the evidence for the transmission of resistant strains through WWTPs to surface waters. DISCUSSION: Results of this study suggest that 1) UTI share a minor participation in hospitals wastewaters; 2) a high diversity of STs and phylogenetic groups in municipal wastewaters derive from the urban influence rather than hospitals; and 3) pathogenic lineages and bacteria with emerging resistance genotypes associated with hospitals spread into surface waters. Our study highlights the contribution of hospital and municipal wastewater to the transmission of ESBL- and carbapenemase-producing E. coli with MDR profiles to the environment.
- MeSH
- antibakteriální látky farmakologie MeSH
- beta-laktamasy genetika MeSH
- Escherichia coli genetika MeSH
- fylogeneze MeSH
- infekce močového ústrojí * mikrobiologie MeSH
- infekce vyvolané Escherichia coli * mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- multilokusová sekvenční typizace MeSH
- nemocnice MeSH
- odpadní voda MeSH
- odpadní vody mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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
OBJECTIVE: The motility and genotype of the flagellin fliC and fliD genes were investigated in 82 Clostridioides difficile isolates belonging to the ribotypes (RTs): 027 (n = 41), 176 (n = 17), 023 (n = 8), 017 (n = 6) and 046 (n = 10). The reference C. difficile strains 630 and M120 were included as controls for the motility assay. METHODS: A Multiple Locus Variable-number Tandem Repeat Analysis (MLVA) was used to exclude the genetic relatedness of C. difficile isolates belonging to the same RT. The variability of the fliC and fliD genes was determined by PCR-restriction fragment length polymorphism (RFLP) analysis and Sanger sequencing. The motility assay was carried out with 0.175% BHI agar tubes and BHI solid media plates with 0.4% agar. RESULTS: The highest motility was observed in C. difficile RT023 isolates (p < 0.01), followed by RTs 027 and 176. C. difficile isolates of RTs 017 and 046 were less motile than RTs 027, 176 and 023 (p < 0.01). The fliC and fliD genes were present in all clinical isolates irrespective of the motility results. In the fliC gene analysis, four different RFLP groups were identified (I, II, VII, X). The fliC group VII was identified in two RTs (027 and 176), whereas the remaining three groups (I, II and X) belonged to a single RT 046, 017 and 023, respectively. The fliD gene analysis identified four new RFLP groups (a, b, c and d). CONCLUSIONS: C. difficile RT023 is highly motile and its motility is comparable to the hypervirulent RT027 and its genetic relative RT176.
- MeSH
- bakteriální proteiny genetika MeSH
- Clostridioides difficile * genetika MeSH
- Clostridioides MeSH
- flagelin genetika MeSH
- genotyp MeSH
- klostridiové infekce * MeSH
- lidé MeSH
- ribotypizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Recently, the recommendations for the treatment of Clostridioides difficile infection (CDI) have been updated. However, in addition to the clinical efficacy data, the drug of choice should ideally represent optimal antimicrobial stewardship, with an emphasis on rapid restoration of the gut microbiota to minimize the risk of infection relapses. Oral administration of metronidazole results in low concentration in stool, and interaction with fecal microbiota reduces its antimicrobial bioactivity. Reported elevated minimum inhibitory concentrations of metronidazole in epidemic C. difficile ribotypes and the emergence of plasmid-mediated resistance to metronidazole represent additional potential risks for clinical failure. If metronidazole is the only CDI treatment option, antimicrobial susceptibility testing on agar containing heme should be performed in C. difficile isolate. Compared with metronidazole, oral vancomycin and fidaxomicin reach very high concentrations in the stool, and therefore can quickly reduce C. difficile shedding. Health care facilities with higher CDI incidence and/or occurrence of epidemic ribotypes should not use metronidazole because prolonged C. difficile shedding can increase the risk for further C. difficile transmission. Only fidaxomicin has a narrow spectrum of antimicrobial activity, which might be, together with persistence on spores, the main contributing factor to reduce the recurrent CDI rates.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- Clostridioides difficile * MeSH
- fidaxomicin terapeutické užití MeSH
- klostridiové infekce * farmakoterapie epidemiologie mikrobiologie MeSH
- lidé MeSH
- metronidazol farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Colistin belongs to the last-resort antibiotics. The discovery of plasmid-bound colistin resistance mediated by the mcr-gene(s) is of great concern because, given its biological potential, there is a risk of its rapid spread. OBJECTIVES: To discuss the current literature on the methods for the screening for mcr-mediated resistance to colistin. SOURCES: Literature was drawn from a search of PubMed from 1 January 2016 to 26 April 2021. CONTENT: The selective culture-based or culture-independent approach can be used for the screening of mcr-mediated resistance to colistin in clinical samples. Rapid Polymyxin NP, Colistin Drop or Colistin Agar Spot tests are applicable for the selection of isolates with a suspected resistance to colistin that has to be confirmed by broth microdilution. The mcr-mediated resistance to colistin can be confirmed by the detection of the causal gene(s) or by phenotype using EDTA-colistin broth disc elution; production of the MCR-1 enzyme can be confirmed with lateral flow immunoassay, using matrix-assisted laser desorption/ionization time-of flight or liquid chromatography-based mass spectrometry. Whole-genome sequencing (WGS) is the ultimate typing method. When a WGS platform is not available at a healthcare facility, a WGS-outsourced service, in combination with freely available bioinformatics tools, allows for the characterization of the mcr-gene(s) carrying isolates. IMPLICATIONS: mcr-mediated colistin resistance should be monitored through active targeted screening. The broth microdilution method is required for colistin susceptibility testing but as only a selected number of clinical isolates are tested, colistin resistance, including mcr-mediated, may remain undetected. In mcr-1-positive Escherichia coli isolates, the MIC to colistin can range from 2 to 8 mg/L, so it is proposed that Enterobacterales with a colistin MIC of 2 mg/L should also be included in the mcr-mediated colistin resistance screening and those with a confirmed mcr-genotype and/or MCR-phenotype should be considered to be colistin-resistant.
