Clostridioides (formerly: Clostridium) difficile infection (CDI) is a major cause of diarrhoea for inpatients as well as outpatients. Usually, CDI is healthcare-associated but the number of ...community-acquired infections is increasing. CDI is generally associated with changes in the normal intestinal microbiota caused by administration of antibiotics. Elderly and immunocompromised patients are at greater risk for CDI and CDI recurrence. Recently, the treatment options of CDI have undergone major changes: current recommendations speak against using metronidazole for primary CDI, fidaxomicin and bezlotoxumab have been added to the treatment armamentarium and microbial replacement therapies have emerged. Several other therapies are undergoing clinical trials. In this article, we review current treatment guidelines, present the most recent data on the options to treat CDI and glance towards future developments.
KEY MESSAGES
The cornerstones for the treatment of CDI are vancomycin and fidaxomicin. Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence.
In recurrent CDI, bezlotoxumab infusion (a monoclonal antibody against C. difficile toxin B) may be considered as an adjunctive therapeutic strategy in addition to the standard care provided to patients with several risk factors for recurrence.
Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI.
Because of widespread use of probiotics, their safety must be guaranteed. We assessed use of Saccharomyces boulardii probiotic yeast from medical records for patients who had Saccharomyces fungemia ...or other clinical Saccharomyces culture findings. We evaluated all Saccharomyces sp. findings at 5 university hospitals in Finland during 2009–2018. We found 46 patients who had Saccharomyces fungemia; at least 20 (43%) were using S. boulardii probiotic. Compared with a control group that had bacteremia or candidemia, the odds ratio for use of an S. boulardii probiotic was 14 (95% CI 4–44). Of 1,153 nonblood culture findings, the history for 125 patients was checked; at least 24 (19%) were using the probiotic (odds ratio 10, 95% CI 3–32). This study adds to published fungemia cases linked to use of S. boulardii probiotic and sheds light on the scale of nonblood Saccharomyces culture findings that are also linked to use of this probiotic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fecal microbiota transplantation(FMT) is effective in recurrent Clostridium difficile infection(r CDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. ...FMT has been suggested as a potential method for an increasing number of new indications besides r CDI. Among our FMT-treated r CDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than r CDI: Salmonella carriage(two patients), trimethylaminuria(two patients), small intestinal bacterial overgrowth(SIBO;one patient), and lymphocytic colitis(one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli(E. coli) carriage. Of the thirteen r CDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with r CDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.
Fecal microbiota transplantation (FMT) is an effective therapy for recurrent
infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT ...corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as
, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.
Fecal microbiota transplantation (FMT) is an effective treatment for recurrent
Clostridioides difficile
infection (rCDI) and it’s also considered for treating other indications. Metagenomic studies ...have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of
Bifidobacterium
populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several
Bifidobacterium
strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient‘s microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.
Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia ...and impaired vaccine response.
To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland.
We performed a cross-sectional study to assess all adult CVID patients followed up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax
were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 µg/mL after vaccination. We further characterized the patients' B cell phenotypes and complications associated with CVID.
In total, 9 patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID." Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow-up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow-up was seen in as many as 16% of "probable CVID" patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication.
The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.
LINKED CONTENTThis article is linked to Lahtinen et al and El‐Salhy et al papers. To view these articles, visit https://doi.org/10.1111/apt.15942 and https://doi.org/10.1111/apt.16112
Aims
Acute heart failure (HF) is a common but ill‐defined clinical entity. We describe patients hospitalised with acute HF in regard of clinical presentation, mortality, and risk factors for an ...unfavourable outcome.
Methods and results
We conducted a prospective study including 312 consecutive patients from two European centers hospitalised with acute HF, defined as new onset or worsening of symptoms and signs of HF within 7 days. The mean age was 73 years and 56% were men. Twenty‐eight percent had de‐novo acute HF and 72% a decompensation of chronic HF. Coronary heart disease (CHD) was the most frequent underlying heart disease, elevated blood pressure >150 mmHg and acute ischemia being the most important triggers. Four percent of the patients had cardiogenic shock, 13% presented with pulmonary edema. LV‐EF was <35%, 35−50% and >50% in 35%, 32% and 33% of the patients, respectively. ICU‐treatment was necessary in 39% of the patients. Thirty‐day mortality (11%) was increased in the presence of shock or elevated troponin T levels. Twelve‐month all‐cause mortality (29%) increased in the presence of shock, left ventricular dysfunction, renal insufficiency, CHD, and age.
Conclusions
This prospective study shows that despite modern treatment, morbidity and mortality of patients hospitalised with acute HF remain high.
Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) and is considered as a treatment for other gastrointestinal (GI) diseases. We ...followed up the relief of symptoms and long-term, over-a-year microbiota stabilization in a 46-year-old man, who underwent FMT for antibiotic-induced, non-CDI colitis nine months after being treated for CDI by FMT. Fecal and mucosal microbiota was analyzed before the second FMT and during 14 months after FMT by using a high-throughput phylogenetic microarray. FMT resolved the symptoms and restored normal GI-function. Microbiota analysis revealed increased bacterial diversity in the rectal mucosa and a stable fecal microbiota up to three months after FMT. A number of mucosa-associated bacteria increased after FMT and some of these bacteria remained increased in feces up to 14 months. Notably, the increased bacteria included Bifidobacterium spp. and various representatives of Clostridium clusters IV and XIVa, such as Clostridium leptum, Oscillospira guillermondii, Sporobacter termitidis, Anaerotruncus colihominis, Ruminococcus callidus, R. bromii, Lachnospira pectinoschiza, and C. colinum, which are presumed to be anti-inflammatory. The presented case suggests a possible role of microbiota in restoring and maintaining normal GI-functionality and improves our knowledge on the etiology of antibiotic-induced, noninfectious colitis.
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