Usability of rectal swabs for microbiome sampling in a cohort study of hematological and oncological patients

Objectives Large-scale clinical studies investigating associations between intestinal microbiota signatures and human diseases usually rely on stool samples. However, the timing of repeated stool sample collection cannot be predefined in longitudinal settings. Rectal swabs, being straightforward to obtain, have the potential to overcome this drawback. Therefore, we assessed the usability of rectal swabs for microbiome sampling in a cohort of hematological and oncological patients. Study design We used a pipeline for intestinal microbiota analysis from deep rectal swabs which was established and validated with test samples and negative controls. Consecutively, a cohort of patients from hematology and oncology wards was established and weekly deep rectal swabs taken during their admissions and re-admissions. Results Validation of our newly developed pipeline for intestinal microbiota analysis from rectal swabs revealed consistent and reproducible results. Over a period of nine months, 418 rectal swabs were collected longitudinally from 41 patients. Adherence to the intended sampling protocol was 97%. After DNA extraction, sequencing, read pre-processing and filtering of chimeric sequences, 405 of 418 samples (96.9%) were eligible for further analyses. Follow-up samples and those taken under current antibiotic exposure showed a significant decrease in alpha diversity as compared to baseline samples. Microbial domination occurred most frequently by Enterococcaceae (99 samples, 24.4%) on family level and Enterococcus (90 samples, 22.2%) on genus level. Furthermore, we noticed a high abundance of potential skin commensals in 99 samples (24.4%). Summary Deep rectal swabs were shown to be reliable for microbiome sampling and analysis, with practical advantages related to high sampling adherence, easy timing, transport and storage. The relatively high abundance of putative skin commensals in this patient cohort may be of potential interest and should be further investigated. Generally, previous findings on alpha diversity dynamics obtained from stool samples were confirmed

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta- lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not nor- malized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk

Screening and contact precautions - A survey on infection control measures for multidrug-resistant bacteria in German university hospitals

To assess the scope of infection control measures for multidrug-resistant bacteria in high-risk settings, a survey among university hospitals was conducted. Fourteen professionals from 8 sites participated. Reported policies varied largely with respect to the types of wards conducting screening, sample types used for screening and implementation of contact precautions. This variability among sites highlights the need for an evidence-based consensus of current infection control policies

Vancomycin-resistant enterococci (VRE): a reason to isolate?

In recent years, an increase in invasive VRE infections has been reported worldwide, including Germany. The most common gene encoding resistance to glycopeptides is VanA, but predominant VanB clones are emerging. Although neither the incidence rates nor the exact routes of nosocomial transmission of VRE are well established, screening and strict infection control measures, e.g. single room contact isolation, use of personal protective clothing by hospital staff and intensified surface disinfection for colonized individuals, are implemented in many hospitals. At the same time, the impact of VRE infection on mortality remains unclear, with current evidence being weak and contradictory. In this short review, we aim to give an overview on the current basis of evidence on the clinical effectiveness of infection control measures intended to prevent transmission of VRE and to put these findings into a larger perspective that takes further factors, e.g. VRE-associated mortality and impact on patient care, into account

Fecal Microbiota Transfer Reliable Indications, Donor Screening, and Modes of Application

Background: Fecal microbiota transfer (FMT) is increasingly being used in Germany, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary. Methods: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad. Results: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI. Conclusion: Encapsulation of the fecal microbiome (FM) and storage at -20 degrees C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active components of the FM. It is not yet clear when the ultimate goal of recombinant production can be achieved

Colonization and infection with extended spectrum beta-lactamase producing Enterobacteriaceae in high-risk patients - Review of the literature from a clinical perspective

Background: The prevalence of extended-spectrum -lactamase producing Enterobacteriaceae (ESBL-E) is increasing worldwide. ESBL-E are known to colonize different body sites and cause bloodstream infections (BSI), pneumonia, intra-abdominal infections and urinary tract infections. Even though ESBL-E-related morbidity and mortality in high-risk patients - patients receiving immunosuppressants or chemotherapy, as well as those treated in an ICU - is considerable, the management of ESBL-E in these populations has not been systematically reviewed. Methods: For the purpose of this review, ICU patients, patients in hematology and oncology wards and transplant recipients were considered high-risk. An English-language Medline search was conducted to identify literature on epidemiology, risk factors, clinical impact and measures of infection control regarding ESBL-E in high-risk patients published between June 2002 and May 2013. Results: Using the above described methodology, 43 relevant articles regarding high-risk patients and - for areas where literature on exclusively high-risk patients is scarce - 17 articles in standard risk settings were identified. The evidence on epidemiology, associated risk factors, treatment and hygiene measures were summarized. Discussion: This review gives a complete overview on the management of ESBL-E in the high-risk setting