Composition and changes of blood microbiota in adult patients with community-acquired sepsis: A pilot study from bench to bedside.

Background: Characteristics of the blood microbiota among adult patients with community-acquired sepsis are poorly understood. Our aim was to analyze the composition of blood microbiota in adult patients with community-acquired sepsis, and correlate changes with non-septic control patients. Methods: A prospective observational study was carried out by including adult patients hospitalized for community-acquired sepsis at our center between January and November 2019, by random selection from a pool of eligible patients. Study inclusion was done on the day of sepsis diagnosis. Community acquisition was ascertained by a priori exclusion criteria; sepsis was defined according to the SEPSIS-3 definitions. Each included patient was matched with non-septic control patients by age and gender in a 1:1 fashion enrolled from the general population. Conventional culturing with BacT/ALERT system and 16S rRNA microbiota analysis were performed from blood samples taken in a same time from a patient. Abundance data was analyzed by the CosmosID HUB Microbiome software. Results: Altogether, 13 hospitalized patients were included, 6/13 (46.2%) with sepsis and 7/13 (53.8%) with septic shock at diagnosis. The most prevalent etiopathogen isolated from blood cultures was Escherichia coli, patients mostly had intraabdominal septic source. At day 28, all-cause mortality was 15.4% (2/13). Compared to non-septic control patients, a relative scarcity of Faecalibacterium, Blautia, Coprococcus and Roseburia genera, with an abundance of Enhydrobacter, Pseudomonas and Micrococcus genera was observed among septic patients. Relative differences between septic vs. non-septic patients were more obvious at the phylum level, mainly driven by Firmicutes (25.7% vs. 63.1%; p<0.01) and Proteobacteria (36.9% vs. 16.6%; p<0.01). The alpha diversity, quantified by the Chao1 index showed statistically significant difference between septic vs. non-septic patients (126 ± 51 vs. 66 ± 26; p<0.01). The Bray-Curtis beta diversity, reported by principal coordinate analysis of total hit frequencies, revealed 2 potentially separate clusters among septic vs. non-septic patients. Conclusion: In adult patients with community-acquired sepsis, specific changes in the composition and abundance of blood microbiota could be detected by 16S rRNA metagenome sequencing, compared to non-septic control patients. Traditional blood culture results only partially correlate with microbiota test results.

Immunologic complications of infections: the relevance of the grey zone / Fertozésekhez kapcsolódó immunológiai jelenségek: a szürkezóna jelentosége.

Összefoglaló. A fertozésekhez kapcsolódó immunológiai kórképekre különösen jellemzo, hogy mind etiológiai tényezoikben, mind klinikai képükben rendkívül heterogének. Az átfedo és inkomplett megjelenési formák nem ritkák, ami a diagnosztika standardizálását nehezíti. Egyes, a fertozésekhez opcionálisan kapcsolódó tünetek megfigyelése már több mint egy évszázaddal ezelott elvezetett a gócelmélet megszületéséhez, amely eredeti formájában leginkább elnagyolt és naiv feltételezéseken alapult. Folyamatosan bovülo ismereteink ugyanakkor egyre több esetben támasztják alá, hogy az átvészelt, esetleg krónikus vagy perzisztáló fertozések, illetve a mikrobiom összetétele számos ponton lehet befolyással immunológiai, metabolikus és endokrin homeosztázisunkra. A jelen munkában az ismert összefüggéseket, illetve a meghaladott feltételezéseket is röviden érintve megkíséreljük a rendelkezésre álló ismereteken keresztül áttekinteni a fertozésekhez kapcsolódó immunológiai jelenségek szürkezónáját, azon kórtani folyamatokat és tüneteket, amelyek létezése igazolható, de terápiás következményeik az egyén szintjén egyelore bizonytalanok. Orv Hetil. 2021; 162(38): 1526-1532. Summary. Immunologic phenomena related to infections are well known to be truly heterogeneous, both regarding their etiology and the clinical picture. Overlapping symptoms and incomplete presentations are not seldom, which often constitute diagnostic challenge. Certain, optional complications of infectious diseases led to the creation of the focal infection theory more than a century ago, although only on the basis of assumptions derived from elusive and naive theories. However, an expanding body of evidence ever since did underline the impact of previous and persistent infections on the immunologic, metabolic and endocrine homeostasis. Besides briefly touching the well-defined diseases, as well as the outdated theories of this field, we aim to provide an overview of the grey zone of infection-related immunologic phenomena, the existence of which is biologically well established, however, their true significance on an individual basis remains uncertain. Orv Hetil. 2021; 162(38): 1526-1532.

Characteristics and predictors of treatment failure with intravenous tigecycline monotherapy among adult patients with severe Clostridioides (Clostridium) difficile infection: a single-centre observational cohort study.

Our aim was to analyze characteristics of treatment failure with intravenous tigecycline monotherapy among adults with severe Clostridioides (Clostridium) difficile infection (CDI). A single-centre observational cohort study was performed between 2014 and 2018. Data were collected by charts review, diagnosis and severity were determined by ESCMID guidelines. Primary outcome was treatment failure, secondary outcomes were in-hospital mortality, relapse, colectomy, and complication rates. Independent predictors of failure were identified using logistic regression. Altogether 110 patients were included, failure occurred in 37.3%. Patients with failure frequently had chronic heart and pulmonary co-morbidities, peritonitis, higher CRP levels, ICU admittance rates and need for total parenteral nutrition and vasopressors. Mostly, CDI-specific mortality and complications contributed to failure. Relapse rates were similar. Chronic pulmonary disease, ileus, total parenteral nutrition, and duration of tigecycline therapy were predictors of failure. We conclude that severe CDI cases with higher risk for tigecycline monotherapy failure might be identified by contributing factors.

Investigation of TGFB1 -1347C>T variant as a biomarker after allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for malignant hematopoietic diseases. Cytokines including transforming growth factor ß1 (TGFß1) play a pivotal role in immune reconstruction, and the development of graft versus host disease (GvHD) or infections. The aim of this study was to investigate the role of TGFB1 gene -1347C>T variant in the outcome of HSCT in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridisation probe method. In case of myeloablative conditioning, donor TGFB1 genotype correlated with overall survival (60-month OS for CC: 62.1 ± 4.8%; CT: 46.8 ± 4.8%; TT: 35.6 ± 9.3%; p = 0.032), which was independent of age, donor type and GvHD prophylaxis in multivariate analysis (HR:2.35, 95%CI:1.35-4.10, p = 0.003). The cumulative incidence of acute GvHD grade III-IV [CC:10%; CT:17%; TT:24%], and non-relapse mortality was higher in TT-carriers (24-month NRM: CC:24%; CT:26%; TT:46%, p = 0.035). We did not find any association between recipient TGFB1 -1347C>T polymorphism and HSCT outcome. Our results suggest that donor TGFB1 -1347C>T may exert an adverse influence on the outcome of myeloablative conditioning transplantation.

Clinical and microbiological characteristics and outcomes of community-acquired sepsis among adults: a single center, 1-year retrospective observational cohort study from Hungary.

BACKGROUND: Community-acquired sepsis is a life-threatening systemic reaction, which starts within ≤72 h of hospital admittance in an infected patient without recent exposure to healthcare risks. Our aim was to evaluate the characteristics and the outcomes concerning community-acquired sepsis among patients admitted to a Hungarian high-influx national medical center. METHODS: A retrospective, observational cohort study of consecutive adult patients hospitalized with community-acquired sepsis during a 1-year period was executed. Clinical and microbiological data were collected, patients with pre-defined healthcare associations were excluded. Sepsis definitions and severity were given according to ACCP/SCCM criteria. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were intensive care unit (ICU) admittance, length-of-stay (LOS), source control and bacteraemia rates. Statistical differences were explored with classical comparison tests, predictors of in-hospital all-cause mortality were modelled by multivariate logistic regression. RESULTS: 214 patients (median age 60.0 ± 33.1 years, 57% female, median Charlson score 4.0 ± 5.0) were included, 32.7% of them (70/214) had severe sepsis, and 28.5% (61/214) had septic shock. Prevalent sources of infections were genitourinary (53/214, 24.8%) and abdominal (52/214, 24.3%). The causative organisms were dominantly E. coli (60/214, 28.0%), S. pneumoniae (18/214, 8.4%) and S. aureus (14/214, 6.5%), and bacteraemia was documented in 50.9% of the cases (109/214). In-hospital mortality was high (30/214, 14.0%), and independently associated with shock, absence of fever, male gender and the need for ICU admittance, but source control and de-escalation of empirical antimicrobial therapy were protective. ICU admittance was 27.1% (58/214), source control was achieved in 18.2% (39/214). Median LOS was 10.0 ± 8.0, ICU LOS was 8.0 ± 10.8 days. CONCLUSIONS: Community-acquired sepsis poses a significant burden of disease with characteristic causative agents and sources. Patients at a higher risk for poor outcomes might be identified earlier by the contributing factors shown above.