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
• Fecal Microbiota Transplantation MeSH
• Clostridium Infections * microbiology   MeSH
• Humans MeSH
• Microbiota * MeSH
• Recurrence MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity. METHODS: An observation cohort study included 271 CDI patients hospitalised between 2013-2016. Univariate logistic regression was used to evaluate the association between patients' clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed. RESULTS: In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI. CONCLUSION: Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Administration, Oral MeSH
• Clostridioides difficile drug effects   MeSH
• Fidaxomicin pharmacology   MeSH
• Hospitalization MeSH
• Clostridium Infections drug therapy   microbiology   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• Metronidazole pharmacology   MeSH
• Recurrence MeSH
• Aged MeSH
• Vancomycin pharmacology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

Narušení mikrobiálního ekosystému střeva dnes představuje významný patogenetický faktor řady onemocnění. Známá je úloha alterace intestinální mikrobioty u rekurentní klostridiové kolitidy (rCDI – recurent Clostridioides difficile infection). Přenosem stolice od zdravého dárce do zažívacího traktu nemocného dokážeme navrátit přirozenou homeostázu střevní mikrobioty, a tím efektivně přerušit "bludný kruh“ chronicky relabující klostridiové infekce. Do budoucna očekáváme dominantně perorální způsob podání fekálního transplantátu v podobě enterosolventních kapslí či komerčně vyráběných fekálních derivátů. Tato cesta podání minimalizuje riziko nežádoucích komplikací, které vzácně pozorujeme při administraci suspenze stolice nazoenterální sondou, endoskopicky nebo rektálním klyzmatem. V posledních letech je transplantace střevní mikrobioty testována i u dalších chorobných stavů, jejichž patogeneze je pravděpodobně asociována s intestinální dysbiózou. V tomto smyslu jsou nejčastěji diskutovány idiopatické střevní záněty, syndrom dráždivého tračníku, jaterní encefalopatie a v posledních letech i "civilizační nemoci“, jako jsou diabetes mellitus 2. typu, roztroušená skleróza, Parkinsonova nemoc či metabolický syndrom. Efekt fekální bakterioterapie je pozorován i při eradikaci multirezistentních bakteriálních kmenů kolonizujících střevo pacientů. U rCDI je dnes v rámci medicíny založené na důkazech fekální bakterioterapie celosvětově akceptovaným a doporučovaným terapeutickým postupem. U ostatních onemocnění se jedná stále o metodu experimentální, na přesvědčivé výsledky randomizovaných kontrolovaných studií prozatím čekáme.

Distortions in intestinal microbial ecosystems are important pathogenetic factors of numerous diseases. The role of alterations in intestinal microbiota in the pathogenesis of recurrent clostridium colitis is well known. A fecal transfer from a healthy donor can restore natural homeostasis in intestinal microbiota and thus disrupt a "vicious circle“ of chronic relapsing clostridium infection. In the future, it should be possible to perform peroral fecal microbiota transplantations using enterosolvent tablets or commercially produced fecal derivatives. This administration route minimises the risk of adverse complications, which are rarely observed when fecal suspensions are administered via a nasoenteral probe, endoscopy, or by rectal clysma. In the past few years, intestinal microbiota transplantation has been used for the treatment of other diseases, the pathogenesis of which is probably associated with intestinal dysbiosis. In this respect, the most discussed issues are idiopathic intestinal inflammations, irritable bowel syndrome, liver encephalopathy and recently, "civilisation diseases“ such as diabetes mellitus type 2, multiple sclerosis, Parkinson‘s disease, and metabolic syndrome. The fecal bacteriotherapy effect is observed also during the eradication of multi-resistant bacterial strains that colonise patients‘ intestines. At present, fecal bacteriotherapy for recurrent clostridium colitis, as a proved medical method, is an accepted and world-wide recommended therapy. As for other diseases, this method is still in the experimental stage. Conclusive results of randomised control trials are expected.

• MeSH
• Drug Resistance, Microbial MeSH
• Dysbiosis MeSH
• Fecal Microbiota Transplantation methods   MeSH
• Clostridium Infections * therapy   MeSH
• Humans MeSH
• Enterocolitis, Pseudomembranous therapy   MeSH
• Gastrointestinal Microbiome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

OBJECTIVE: Clostridium difficile infection (CDI) has become one of the most common causes of hospital-acquired infections. Fidaxomicin is one of the latest antibiotics used in the treatment of CDI, however, treatment cost affects recommendations for its use in several countries. We have analysed the treatment of our patients with CDI, treated by fidaxomicin since it was introduced to the market in 2018 and became available in the second biggest Slovak hospital, University Hospital of L. Pasteur. Our aim was to determine efficacy and safety of fidaxomicin in the treatment of CDI in Slovak patients. METHODS: We reviewed all courses of fidaxomicin use in our hospital (n = 60). Fidaxomicin was used for first recurrence (12 times), second recurrence (4 times), third recurrence (2 times), and fifth recurrence (1 patient). 41 patients received fidaxomicin first-line. RESULTS: Success of fidaxomicin treatment was recorded at 86.7% within the whole cohort. In the recurrent Clostridium difficile infection (rCDI) subgroup, fidaxomicin was 63% effective with three patients dying (15.7%) and two patients developing subsequent rCDI. During the duration of the study, 6 patients in total died. Only one of three patients, with three or more recurrences of CDI, had no further presentations after eight weeks of completion of treatment. CONCLUSIONS: The biggest benefit from fidaxomicin treatment was shown in a cohort of patients with primary CDI infection demonstrating a low recurrence rate and significant reduction of fidaxomicin effectiveness in preventing a recurrence when treating patients with multiple rCDI.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Clostridioides difficile drug effects   isolation & purification   MeSH
• Child MeSH
• Adult MeSH
• Fidaxomicin therapeutic use   MeSH
• Clostridium Infections diagnosis   drug therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Slovakia MeSH

Waldenströmova makroglobulinemie je definována přítomností monoklonálního imunoglobulinu typu IgM (M-IgM) a průkazem lymfoplazmocytární infiltrace kostní dřeně. Choroba má indolentní průběh, léčba se zahajuje až v okamžiku, jakmile začne nemoc poškozovat svého nositele. Za klasické indikace k zahájení léčby jsou považovány: B symptomy, symptomatická lymfadenopatie či splenomegalie, anémie s hodnotou hemoglobinu < 100 g/l nebo trombocytopenie < 100 × 109/l, způsobená lymfoplazmocytární infiltrací kostní dřeně. Mezi časté indikace pro zahájení léčby patří klinické známky hyperviskozity či kryoglobulinemie. M-IgM mívá až v 50 % charakter autoprotilátky, která může poškozovat organizmus, a proto jakékoliv prokázané poškození organizmu autoimunitní aktivitou M-IgM je také indikací k léčbě. Přehled vzácných i velmi vzácných typů poškození organizmu autoimunitní aktivitou M-IgM je obsažen v textu. Pro iniciální léčbu se doporučuje kombinace rituximabu, cyklofosfamidu a dexametazonu (RCD), případně doplněná na režim R-CHOP (rituximab, cyklofosfamid, vinkristin, doxorubicin a prednison). V našem souboru 43 pacientů dosáhla léčba kombinací R-CHOP celkem 3 (8,1 %) kompletních remisí a 31 (83,8 %) parciálních remisí. Trvání remise bylo u 75 % léčených delší než 3 roky. V případě recidivy po více než 2 letech lze použít tu samou léčbu, v případě recidivy v kratším intervalu se doporučují jiná léčebná schémata. Vysokodávkovaná chemoterapie s autologní transplantací kmenových krvetvorných buněk získaných z periferní krve se doporučuje až při první recidivě pro osoby mladší 65 let bez kontraindikací. V textu je analyzován přínos nových léků pro léčbu Waldenströmovy makroglobulinemie (bendamustinu, talidomidu, lenalidomidu, ibrutinibu a vysokodávkované chemoterapie). Klíčová slova: autoimunita – bendamustin – bortezomib – hyperviskozita – ibrutinib – kryoglobulinemie – monoclonal immunoglobuline releated disease – nemoc chladových aglutininů – rituximab – Waldenströmova makroglobulinemie

Waldenström macroglobulinemia is defined by the presence of monoclonal immunoglobulin IgM type (M-IgM) and evidence of lymphoplasmacytic bone marrow infiltration. The disease has an indolent course, the treatment is only initiated when the disease has begun to damage its carrier. The following symptoms are regarded as proven indications for initiating therapy: B symptoms, symptomatic lymphadenopathy, splenomegaly, anemia with hemoglobin below 100 g / l or thrombocytopenia < 100 × 109/l, caused by lymphoplasmacytic bone marrow infiltration. Frequent indications for initiating treatment include clinical evidence of hyperviscosity or cryoglobulinemia. M-IgM tends to have a character of autoantibody reaching up to 50 %, which may harm the organism, and therefore any proven damage to the organism by an autoimmune activity of M-IgM is also an indication for treatment. The text includes an overview of rare and very rare types of damage to the organism by M-IgM autoimmune activity. A combination of rituximab, cyclophosphamide and dexamethasone (RCD) is recommended for the initial treatment, possibly extended to R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone). In our cohort of 43 patients the therapy involving a combination of R-CHOP achieved 3 (8.1 %) complete remissions and 31 (83.8 %) partial remissions. The remission in 75 % of the patients lasted more than 3 years. In case of recurrence after > 2 years, the same therapy can be used, in case of a relapse within a shorter period of time different treatment schedules are recommended. High-dose chemotherapy with an autologous transplant of stem cells obtained from peripheral blood is only recommended after the first recurrence for people under 65 years of age without contraindications. The text analyses the benefits of the new drugs for the treatment of Waldenström macroglobulinemia (bendamustine, thalidomide, lenalidomide, ibrutinib and high-dose chemotherapy). Key words: autoimmunity – bendamustine – bortezomibe – hyperviscosity – ibrutinib – cryoglobulinemia – monoclonal immunoglobulin related disease – cold agglutinin disease – rituximab – Waldenström macroglobulinemia

• MeSH
• Chemotherapy, Adjuvant MeSH
• Bortezomib analogs & derivatives   pharmacology   MeSH
• Cytogenetic Analysis MeSH
• Hepatitis C MeSH
• Immunoglobulin M analysis   MeSH
• Remission Induction MeSH
• Disease Attributes MeSH
• Drug Therapy, Combination MeSH
• Cryoglobulinemia MeSH
• Middle Aged MeSH
• Humans MeSH
• Antibodies, Monoclonal pharmacology   MeSH
• Oligopeptides MeSH
• Prognosis MeSH
• Pyrazoles MeSH
• Pyrimidines pharmacology   MeSH
• Rituximab administration & dosage   therapeutic use   MeSH
• Severity of Illness Index MeSH
• Vidarabine analogs & derivatives   pharmacology   MeSH
• Waldenstrom Macroglobulinemia * diagnosis   epidemiology   immunology   pathology   therapy   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Manuál pro aplikaci Typizované ABC kalkulace ve zdravotnických organizacích představuje dokument, který má napomoci praktické implementaci typizované ABC kalkulace, která byla definována jako výstup výzkumného projektu IGA/MZČR „Aplikace moderních kalkulačních metod pro účely optimalizace nákladů ve zdravotnictví“ NT 12235-3/2011.

• MeSH
• Health Care Economics and Organizations MeSH
• Costs and Cost Analysis economics   methods   MeSH
• Accounting MeSH
• Health Facilities economics   MeSH
• Publication type
• Handbook MeSH

• Conspectus
• Účetnictví
• NML Fields
• ekonomie, ekonomika, ekonomika zdravotnictví

• Keywords
• refrakterní celiakie (RCD), RCDI, RCDII,
• MeSH
• Biopsy * methods   utilization   MeSH
• Celiac Disease * diagnosis   complications   mortality   prevention & control   MeSH
• Diet Therapy MeSH
• Diagnosis, Differential MeSH
• Double-Balloon Enteroscopy * trends   utilization   MeSH
• Endoscopy methods   utilization   MeSH
• Immunohistochemistry utilization   MeSH
• Interleukin-15 antagonists & inhibitors   administration & dosage   pharmacology   MeSH
• Capsule Endoscopy * trends   utilization   MeSH
• Humans MeSH
• Lymphoma diagnosis   complications   MeSH
• Multiplex Polymerase Chain Reaction utilization   MeSH
• Pathological Conditions, Signs and Symptoms MeSH
• Malnutrition MeSH
• Prognosis MeSH
• Flow Cytometry utilization   MeSH
• Research MeSH
• Check Tag
• Humans MeSH

Léčba Waldenströmovy makroglobulinemie se zahajuje až při klinických symptomech Při projevech hyperviskozity je indikována léčebná plazmaferéza. Při volbě léčebného postupu je třeba přihlédnout k míře cytopenie. Při závažné neutropenii či trombocytopenbii je vhodné podat rituximab v monoterapii, lépe však s dexametazonem, anebo v kombinaci s talidomidem případně s bortezomibem. Za vhodnou iniciální léčbu se obecně považuje kombinace rituximab + alkylační cytostatikum (anebo kombinace cytostatik) + kortikoidy ve vyšší dávce. Pro pacienty bez závažné cytopenie je vhodné schéma R-CHOP (rituximab, cyklofosfamid, doxorubicin, vinkristin a prednison). Tato léčba dosahuje až 9 % kompletních remisí a 94 % celkových léčebných odezev. S prohlubováním cytopenie je vhodné ubírat intenzitu cytostatické léčby a upřednostnit chemoterapii R-COP (rituximab, vinkristin, cyklofosfamid a prednison), případně RCD (rituximab, cyklofosfamid a dexametazon). U starších pacientů je možné použít chlorambucil v kombinaci s rituximabem. Trojkombinace RCD je používána jako standardní léčba jak v USA na Mayo Clinic, tak v Evropě skupinou European Myeloma Network. Pokud léčebná odezva trvala alespoň 2 roky, lze při relapsu použít stejný léčebný postup jako v iniciální léčbě. Je-li trvání léčebné odezvy kratší než 2 roky, je vhodné použití vysokodávkované chemoterapie s autologní transplantací krvetvorné tkáně, pokud vzhledem k věku a komorbiditám přichází v úvahu. Pokud ne, volíme léčebný režim sestavený z léků, které mají prokázanou účinnost při léčbě Waldenströmovy makroglobulinemie a které nebyly použity v rámci léčby první linie (purinové analogum + rituximab + alkylační cytostatikum). Novými léky pro toto onemocnění jsou bortezomib a bendamustin. Monoterapie bortezomibem dosahuje 60–85% lečebné odezvy v rámci léčby druhé a další linie. Léčba bendamustinem v kombinaci s rituximabem dosáhla vyšší počet léčebných odezev o delším trvání než léčba kombinací R-CHOP.

Therapy of Waldenström´s macroglobulinaemia (WM) is indicated in patients with clinically relevant symptoms. Therapeutic plasmapheresis should be performed in cases with hyperviscosity. The intensity of chemotherapy should be adjusted to the degree of cytopenia. Monotherapy with rituximab is recommended in cases with severe cytopenia, also combination of rituximab with dexamethasone should be possible. Patients with symptomatic WM without severe cytopenia should received a rituximab-containing regimens, optimal variant is combination of rituximab + dexamethasone + alkylation drug (such as cyclophosphamide or bendamustine). Possible treatment combinations are for instance R-CHOP (rituximab, cyclophosphamide, vincristine, and prednisone), R-COP (rituximab, cyclophosphamide, and prednisone), or RCD (rituximab, cyclophosphamide, and dexamethasone). The choice of regimen in individual patients will take into consideration performance status, clinical features including renal function, comorbidities and potential candidacy for stem cell transplantation.Chlorambucil and rituximab is possible treatment options for older patients. The choice of treatment of WM relapse depends on the time of treatment response. Retreatment with primary therapy may be appropriate in patients with duration of treatment response at least 2 years. Other treatment possibilities for WM relapse are regimens containing fludarabine, cladribine or bortezomib. Autologous transplantation of peripheral blood stem cells is feasible therapeutic option for relapsed WM in younger, fitter patients with aggressive chemosensitive disease.

• Keywords
• nemoc chladových aglutininů, bendamustin, hyperviskozita, nemoci způsobené monoklonálním imunoglobulinem, fludarabin, 2-chlorodeoxyadenozin,
• MeSH
• Antineoplastic Agents, Alkylating administration & dosage   therapeutic use   MeSH
• Anemia MeSH
• Anthracyclines administration & dosage   therapeutic use   MeSH
• Bortezomib MeSH
• Chlorambucil administration & dosage   therapeutic use   MeSH
• Cyclophosphamide administration & dosage   therapeutic use   MeSH
• Glucocorticoids administration & dosage   therapeutic use   MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   therapeutic use   MeSH
• Immunoglobulin M immunology   blood   MeSH
• Immunologic Factors administration & dosage   therapeutic use   MeSH
• Cladribine administration & dosage   therapeutic use   MeSH
• Hematologic Diseases complications   MeSH
• Cryoglobulinemia drug therapy   complications   MeSH
• Boronic Acids administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Prognosis MeSH
• Antineoplastic Agents administration & dosage   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols * administration & dosage   therapeutic use   MeSH
• Pyrazines administration & dosage   therapeutic use   MeSH
• Rituximab MeSH
• Nitrogen Mustard Compounds administration & dosage   therapeutic use   MeSH
• Vidarabine administration & dosage   therapeutic use   MeSH
• Blood Viscosity MeSH
• Waldenstrom Macroglobulinemia * diagnosis   drug therapy   physiopathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• MeSH
• Administration, Rectal MeSH
• Neoplasms, Experimental MeSH
• Injections, Subcutaneous MeSH
• Models, Animal MeSH
• Mice, Nude MeSH
• Cell Line, Tumor drug effects   MeSH
• Lung Neoplasms drug therapy   MeSH
• Enzyme Precursors administration & dosage   MeSH

• Conspectus
• Farmacie. Farmakologie
• NML Fields
• farmacie a farmakologie
• onkologie
• pneumologie a ftizeologie
• NML Publication type
• studie

• MeSH
• Administration, Rectal MeSH
• Neoplasms, Experimental MeSH
• HCT116 Cells drug effects   MeSH
• Injections, Subcutaneous MeSH
• Colorectal Neoplasms drug therapy   MeSH
• Models, Animal MeSH
• Mice, Nude MeSH
• Enzyme Precursors administration & dosage   MeSH

• Conspectus
• Farmacie. Farmakologie
• NML Fields
• farmacie a farmakologie
• onkologie
• gastroenterologie
• NML Publication type
• studie