Implementation of an antimicrobial stewardship program in the Vascular Surgery ward of a university tertiary care hospital in Pavia, Northern Italy.

PURPOSE: The commitment of multidisciplinary teams in antimicrobial stewardship programs (ASPs) is often inadequately considered, especially in surgical wards. We wanted to evaluate clinical, microbiological, and pharmacological outcomes before and after the implementation of an ASP in the Vascular Surgery ward of Fondazione IRCCS Policlinico San Matteo, a tertiary care hospital in Pavia, Italy. METHODS: This was a quasi-experimental quality-improvement study. The antimicrobial stewardship activity was conducted twice a week for 12 months and consisted of both prospective audit and feedback of all the ongoing antimicrobial prescriptions by the infectious diseases' consultants and educational meetings for the healthcare workers of the Vascular Surgery ward. For comparison between the study periods, Student t test (Mann-Whitney test for skewed distributions) was used for quantitative variables (ANOVA or Kruskall-Wallis for > 2 groups respectively), and Pearson's chi-squared test (Fisher exact test where appropriate) for categorical variables. 2-tailed tests were used. P-value significance cut-off was 0.05. RESULTS: During the 12-month intervention period, among a total number of 698 patients, 186 prescriptions were revised, mostly leading to de-escalating an ongoing antimicrobial therapy (39, 20.97%). A statistically significant reduction in isolates of carbapenem-resistant Pseudomonas aeruginosa (p-value 0.003) and the absence of Clostridioides difficile infections were reported. No statistically significant changes were observed in terms of length of stay and all-cause in-hospital mortality. A significant decrease in the administration of carbapenems (p-value 0.01), daptomycin (p-value < 0.01) and linezolid (p-value 0.43) was registered. A significant reduction in antimicrobial costs was also observed. CONCLUSIONS: The implementation of a 12-month ASP brought significant clinical and economic results, highlighting the benefits of a multidisciplinary teamwork.

Epidemiological Characterization of Listeria monocytogenes Infections in Pavia Province in 2017 Reveals the Presence of Multiple Concurrently Circulating Strains.

Consumption of raw food, especially smoked fish, meat, soft cheeses, and vegetables, contaminated with Listeria monocytogenes can cause listeriosis, which can be invasive in pregnant women, elderly, and immunocompromised and diabetic patients. Through June to November of 2017, 11 patients developed invasive listeriosis in a small area of northern Italy. In the same period, 15 food samples (ready-to-eat seafood, raw vegetables, cheese samples, and salami) collected during the routine screening programs in the same area were found to be contaminated with L. monocytogenes. We characterized the isolates to determine the relatedness of L. monocytogenes strains isolated from patients and isolates from food samples and food-processing plants. Whole genome sequencing analysis showed that multiple L. monocytogenes strains were circulating in the area and no association was found between clinical and food isolates.

Migrations do not modify Mycobacterium tuberculosis resistance rates: a 20-year retrospective study.

Tuberculosis (TB) caused by resistant strains is becoming a public health concern also in high-income countries. In Pavia province, Northern Italy, the prevalence of foreign-born has increased in recent years. Nevertheless, it is unclear if this has modified epidemiology and resistance patterns of Mycobacterium tuberculosis. We retrospectively collected data on all the Mycobacterium tuberculosis strains isolated by culture in the microbiology reference laboratory of the province of Pavia from 01/01/1998 to 31/12/2017. Overall, 919 patients were identified, 320 were foreign-born (34.8%). The proportion of cases due to foreign-born patients increased during the study period as did resistance to isoniazid (INH) (p = 0.01), while resistance to rifampicin (RIF) did not (p = 0.8). INH and RIF resistance were comparable among Italian and foreign-born patients (7.9% vs 9.7% for INH and 4% vs 5% for RIF, respectively). Twenty-height (3.05%) patients harboured MDR strains. Prevalence of MDR strains was not different between Italians and foreign-born patients (2.8% vs 3.4%, p = 0.6). During the study period the proportion of TB cases due to foreign-born patients and INH resistance increased. This increase was equal among Italian and foreign-born patients. Migrants in our area are not a driver of resistance to anti-mycobacterial drugs.

Bloodstream infections caused by Escherichia coli carrying mcr-1 gene in hospitalized patients in northern Italy from 2012 to 2018.

PURPOSE: The recurrence of multi-drug resistant (MDR) pathogens to the latest antibiotics and the limited development of new antibacterial agents have reduced the options for the treatment of severe infections. The reintroduction of old antibiotics, such as colistin, represents an effective strategy, since the latest antibiotics are over-consumed and ineffective against MDR pathogens. In 2015, Liu (Lancet Infect Dis 16:161-168, 2016) reported Escherichia coli (E. coli) isolates carrying plasmid-mediated colistin resistance gene mcr-1. The first of mcr-1 positive colistin-resistant (col-R) E. coli from a human blood culture was observed in 2012 in Latin America, while in Italy was reported for the first time by our center in 2016. The present study aimed to describe the prevalence of mcr-1 positive col-R strains in E. coli-related bloodstream infection among patients hospitalized in Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, from 2012 to 2018, including the three cases already published. METHODS: All col-R E. coli strains isolated from blood cultures collected during the study period were analyzed. The minimal inhibitory concentration of colistin was determined using broth microdilution and detection of mcr-1 and mcr-2 genes was performed by PCR. The sequence type of E. coli mcr-1 positive was determined according to Multilocus sequence typing. RESULTS: Out of 1557 samples, 14 strains (0.90%) were col-R. and positive for the presence of the mcr-1 gene, with no mcr-2 detected. The most common ST was ST10 (n = 3), followed by ST410 (n = 2). The remaining strains exhibited different MLST profiles, indicating that they were genetically unrelated. CONCLUSIONS: Proper reporting of the presence of mcr-1 genes is an essential component to anticipate the spread of colistin resistance. This public health issue is particularly alarming in Italy due to the consistent circulation of MDR bacteria.

The Possible Role of Gut Microbiota and Microbial Translocation Profiling During Chemo-Free Treatment of Lymphoid Malignancies.

The crosstalk between gut microbiota (GM) and the immune system is intense and complex. When dysbiosis occurs, the resulting pro-inflammatory environment can lead to bacterial translocation, systemic immune activation, tissue damage, and cancerogenesis. GM composition seems to impact both the therapeutic activity and the side effects of anticancer treatment; in particular, robust evidence has shown that the GM modulates the response to immunotherapy in patients affected by metastatic melanoma. Despite accumulating knowledge supporting the role of GM composition in lymphomagenesis, unexplored areas still remain. No studies have been designed to investigate GM alteration in patients diagnosed with lymphoproliferative disorders and treated with chemo-free therapies, and the potential association between GM, therapy outcome, and immune-related adverse events has never been analyzed. Additional studies should be considered to create opportunities for a more tailored approach in this set of patients. In this review, we describe the possible role of the GM during chemo-free treatment of lymphoid malignancies.

FilmArray™ GI panel performance for the diagnosis of acute gastroenteritis or hemorragic diarrhea.

BACKGROUND: Acute gastroenteritis is a common cause of morbidity and mortality in humans worldwide. The rapid and specific identification of infectious agents is crucial for correct patient management. However, diagnosis of acute gastroenteritis is usually performed with diagnostic panels that include only a few pathogens. In the present bicentric study, the diagnostic value of FilmArray™ GI panels was assessed in unformed stool samples of patients with acute gastroenteritis and in a series of samples collected from pediatric patients with heamorragic diarrhea. The clinical performance of the FilmArray™ gastrointestinal (GI) panel was assessed in 168 stool samples collected from patients with either acute gastroenteritis or hemorragic diarrhea. Samples showing discordant results between FilmArray and routine methods were further analyzed with an additional assay. RESULTS: Overall, the FilmArray™ GI panel detected at least one potential pathogen in 92/168 (54.8%) specimens. In 66/92 (71.8%) samples, only one pathogen was detected, while in 26/92 (28.2%) multiple pathogens were detected. The most frequent pathogens were rotavirus 13.9% (22/168), Campylobacter 10.7% (18/168), Clostridium difficile 9.5% (16/168), and norovirus 8.9% (15/168). Clostridium difficile was identified only in patients with acute gastroenteritis (p < 0.01), while STEC was detected exclusively in patients with hemorragic diarrhea (p < 0.01). In addition, Campylobacter spp., Salmonella spp., EPEC and E. coli producing Shiga-like toxin were more frequently detected in patients with hemorragic diarrhea (p < 0.05). The overall percent agreement calculated in samples was 73.8% and 65.5%, while 34.5% were discordant. After additional confirmatory analyses, the proportion of discordant samples decreased to 7.7%. Rotavirus and astrovirus were the most frequently unconfirmed pathogens. CONCLUSION: In conclusion, the FilmArray™ GI panel has proved to be a valuable new diagnostic tool for improving the diagnostic efficiency of GI pathogens.

Three cases of mcr-1-positive colistin-resistant Escherichia coli bloodstream infections in Italy, August 2016 to January 2017.

We describe three cases of bloodstream infection caused by colistin-resistant Escherichia coli in patients in a tertiary hospital in Italy, between August 2016 and January 2017. Whole genome sequencing detected the mcr-1 gene in three isolated strains belonging to different sequence types (STs). This occurrence of three cases with mcr-1-positive E. coli belonging to different STs in six months suggests a widespread problem in settings where high multidrug resistance is endemic such as in Italy.

A catheter-related bloodstream infection caused by Chryseobacterium indologenes successfully treated with antibiotic-lock rescue therapy.

We report the case of a catheter-related bloodstream infection caused by Chryseobacterium indologenes, an uncommon and multi-resistant pathogen, in a pediatric patient with a long-term vascular access device placed for chemotherapy treatment. The infection was successfully treated with ciprofloxacin antibiotic-lock therapy. This is the first report on successful salvage of a long-term device colonized by multi-resistant Chryseobacterium indologenes.

Glycosylation of Recombinant Antigenic Proteins from Mycobacterium tuberculosis: In Silico Prediction of Protein Epitopes and Ex Vivo Biological Evaluation of New Semi-Synthetic Glycoconjugates.

Tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (LAM), with antigenic proteins from Mycobacterium tuberculosis (MTB), has been proposed as a new strategy for developing efficient vaccines. In this work, we investigated the effect of the chemical glycosylation on two recombinant MTB proteins produced in E. coli with an additional seven-amino acid tag (recombinant Ag85B and TB10.4). Different semi-synthetic glycoconjugated derivatives were prepared, starting from mannose and two disaccharide analogs. The glycans were activated at the anomeric position with a thiocyanomethyl group, as required for protein glycosylation by selective reaction with lysines. The glycosylation sites and the ex vivo evaluation of the immunogenic activity of the different neo-glycoproteins were investigated. Glycosylation does not modify the immunological activity of the TB10.4 protein. Similarly, Ag85B maintains its B-cell activity after glycosylation while showing a significant reduction in the T-cell response. The results were correlated with the putative B- and T-cell epitopes, predicted using a combination of in silico systems. In the recombinant TB10.4, the unique lysine is not included in any T-cell epitope. Lys30 of Ag85B, identified as the main glycosylation site, proved to be the most important site involved in the formation of T-cell epitopes, reasonably explaining why its glycosylation strongly influenced the T-cell activity. Furthermore, additional lysines included in different epitopes (Lys103, -123 and -282) are also glycosylated. In contrast, B-cell epitopic lysines of Ag85B were found to be poorly glycosylated and, thus, the antibody interaction of Ag85B was only marginally affected after coupling with mono- or disaccharides.

Colistin inhibits E. coli O157:H7 Shiga-like toxin release, binds endotoxins and protects Vero cells.

The role of antibiotics in the treatment of Shiga-like toxin (Stx)-producing E. coli infection is still controversial. This study investigated the effects of colistin on Vero cell cytotoxicity caused by the enterohemorrhagic EC O157:H7, and the effects of colistin on Stx and endotoxin release by EC O157:H7. Vero cells were incubated with supernatant collected from EC O157:H7 cultured for 18 h without (control) or with various concentrations of colistin. In the absence of colistin, Vero cell viability after 48 h was 29.1±6.5%. Under the same conditions, the overnight presence of colistin reduced cytotoxicity to Vero cells (viability: 97±3.5 to 56.5±14.4% for colistin concentrations ≥MIC). Sub-MIC concentrations of colistin also provided partial protection (viability: 38.8±12.5 to 36.6±14% for 0.125 and 0.06 mcg/ml colistin, respectively). Endotoxins contributed to the cytotoxic effects on Vero cells since lower but still significant protection was observed when colistin was added directly to the supernatant collected from cultures of untreated EC O157:H7. Colistin reduced Stx release in a concentration-dependent manner, also at sub-MIC concentrations. Coincubation of the supernatant from EC O157:H7 cultures with colistin markedly reduced the endotoxin concentration at all doses investigated. In conclusion, colistin protects Vero cells from EC O157:H7 at supra- and sub-MIC concentrations by inhibiting Stx release and binding endotoxins. Colistin might be a valuable treatment for clinically severe forms of EC O157:H7 infection.

Epidemiology of Mycobacterium tuberculosis infection in Pavia province, Lombardy, Northern Italy, 1998-2013.

This study investigated the epidemiology of tuberculosis in the last 16 years in the province of Pavia, Lombardy, Northern Italy. The objective was to evaluate the clinical pattern of tuberculosis in immigrant groups compared with Italians in an observational retrospective study conducted from 1998 to 2013. In all, 615 tuberculosis cases were admitted, 354 males (57.3%), median age 47-years, 425 (69.1%) Italian-born patients, 190 (30.9%) immigrants. The ratio between the immigrant group and the Italian-born group of patients increased from 1.7% to 54.5% in the study period (p=0.001). HIV was the most common comorbidity, affecting 48 patients (7.8%), followed by diabetes in 35 (5.7%) and COPD in 30 (4.9%). The overall admission-associated mortality was 5.5%. Italian-born patients were older than non-Italian born subjects and had at least one comorbidity, 162 (38.1%) and 22 (11.6%), respectively (p<0,0001). Mortality was increased among Italian-born compared with non-Italian-born patients (7.3% versus 1.6%, p=0.004). No significant variation in extra-pulmonary tuberculosis (EPTB) prevalence occurred. Considering specific form of EPTB, HIV infection was associated with an increased risk of EPTB (RR 2.02, 95%CI 1.09-3.74, p=0.026). There was a high risk of tuberculosis among immigrants, whereas a decreasing trend was consistently observed among Italian-born patients. Italian-born patients show a higher tuberculosis-associated mortality risk due to older age and comorbidities.

Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

Genomic epidemiology of Klebsiella pneumoniae in Italy and novel insights into the origin and global evolution of its resistance to carbapenem antibiotics.

Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated with K. pneumoniae infections in nosocomial environments. We sequenced the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty-one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ∼ 1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding of K. pneumoniae evolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy.

Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole-Genome Analysis: Small-Scale Italian Scenario within a Single Hospital.

Multidrug-resistant (MDR) Klebsiella pneumoniae is one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistant K. pneumoniae strains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the "Italian scenario." We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistant K. pneumoniae isolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity of K. pneumoniae strains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens.

Epidemiological characteristics of bloodstream infections in patients with different degrees of liver disease.

Observational retrospective study to evaluate the etiology, the outcome and the risk factors of bloodstream infections (BSIs) in patients with liver disease. One hundred and forty-eight BSIs were diagnosed (infection rate: 0.60 per 100 days of hospital stay), 62 BSIs (41.9 %) were associated with Gram-positive bacteria (infection rate: 0.25 per 100 days of hospital stay) and 80 (54.4 %) with Gram-negative bacteria (infection rate: 0.32 per 100 days of hospital stay). Admission-associated mortality was higher in patients with BSI than in those without BSI (20.6 versus 5.0 %, p < 0.001). Patients with cirrhosis had an increased risk to develop a BSI compared with patients with chronic hepatitis, specifically for Gram-positive (and Staphylococcus spp)-related BSI.

Neutrophil CD64 expression: a reliable diagnostic marker of infection in advanced cancer patients?

Infection and sepsis are major health problems in cancer patients. There is a need for the identification and validation of biomarkers to improve their early diagnosis and treatment. Emerging evidence showed that neutrophil CD64 is a highly sensitive and specific marker for systemic infection and sepsis in critically ill patients with various diseases but data on patients bearing solid tumors are still lacking. Using a dedicated flow cytometric assay we evaluated neutrophil CD64 expression in patients with advanced cancer without active infections to verify if it could be utilized as a reliable biomarker of early infections also in oncologic patients.

Post-exposure rate of tuberculosis infection among health care workers measured with tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital.

BACKGROUND: This study assesses the risk of LTBI at our Hospital among HCWs who have been exposed to TB patients with a delayed diagnosis and respiratory protection measures were not implemented. METHODS: All HCWs exposed to a patient with cultural confirmed pulmonary TB and respiratory protection measures were not implemented were included. Data on TST results performed in the past (defined as T0) were recorded. TST was performed twice: first, immediately after exposure to an index patient (T1) and three months later (T2). The period of time between T0 and T1 was used to calculate he annual rate of tuberculosis infection (ARTI), while le period of time between T1 and T2 was used to calculate the post exposure annual rate of tuberculosis infection (PEARTI). RESULTS: Fourteen index patients were admitted; sputum smear was positive in 7 (58.3%), 4 (28.6%) were non-Italian born patients. 388 HCWs were exposed to index patients, a median of 27 (12-39) HCW per each index patient. One hundred eighty (46.4%) HCWs received BCG in the past. One hundred twenty two HCWs (31%) were TST positive at a previous routine screening and not evaluated in this subset. Among the remaining 255 HCWs with negative TST test in the past, TST at T1 was positive in 11 (4.3%). ARTI was 1.6 (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, that were TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100 PY. At univariate analysis, older age was associated with post exposure latent tuberculosis infection (HR 1.12; 95% CI 1.03-1.22, p=0.01). CONCLUSIONS: PEARTI was considerably higher among HCWs exposed to index patients than ARTI. These data underscore the overwhelming importance of performing a rapid diagnosis, as well as implementing adequate respiratory protection measures when TB is suspected.

Antibacterial activity and cytotoxic effect of SIAB-GV3.

The aim of this study was to evaluate the antibacterial activity and cytotoxic effect of the compound SIAB-GV3, a new formulation presenting as an aqueous suspension of silicon dioxide (SiO2) functionalized with silver (Ag+) nanoparticles and benzalkonium. The product is formulated as an adjuvant for the treatment of inflammatory diseases of the oral cavity. This study demonstrates that SIAB-GV3 possesses strong antimicrobial activity against most of the common oral pathogens, in particular against Streptococcus pyogenes, Porphyromonas gingivalis and Aggregatibacter actinimycetemcomitans. The cytotoxic effect against human embryo lung fibroblasts (HELF cells) was evaluated at different times, from 1 h to 168 h, using concentrations of SIAB-GV3 ranging from 50 mg/ml to 0.0008 mg/ml. At the concentration of 10 mg/ml, commonly used in clinical practice, the compound results cyto- toxic after about 2 hours, this time being much longer than the typical time of local application, which is no more than 10 minutes. In conclusion, our findings suggest that SIAB-GV3 has a good antibacterial activity against the most common oral pathogens even at very low concentrations and a low cytotoxic activity, thanks to the synergistic effects of Ag nanoparticles, silicon dioxide and benzalkonium.

Patients with Whipple's disease have a high prevalence of Helicobacter pylori infection.

INTRODUCTION: Whipple's disease is a rare systemic infection due to an impaired immunological response against T. whipplei in genetically predisposed individuals. Since we previously noted development of H. pylori related complications in some patients with Whipple's disease, our aim was to study the prevalence of H. pylori infection and H. pylori related disorders in Whipple's disease. METHODS: Whipple's disease patients diagnosed from Jan-2002 to Dec-2021 and two controls per patient, matched for age, gender, ethnicity and year of H. pylori testing were enrolled. RESULTS: 34 patients with Whipple's disease and 68 controls were enrolled. H. pylori infection (13/34 vs 8/68, p<0.01), H. pylori-related gastritis (p<0.01) and gastric atrophy (p = 0.01) were significantly more common in patients with Whipple's disease than controls. H. pylori infection and Whipple's disease were diagnosed synchronously in 6/13 patients, and during follow-up in the remaining 7. Interestingly, these last 7 patients were all on trimethoprim-sulfamethoxazole long-term therapy. Two patients developed H. pylori-related gastric malignancies during follow-up. No patients on doxycycline developed H. pylori infection. CONCLUSIONS: H. pylori infection and related disorders are common in patients with Whipple's disease and should always be excluded both at time of diagnosis and during follow-up. These findings should be taken into account when selecting antibiotics for Whipple's disease long-term prophylaxis.

Reduction of BSI associated mortality after a sepsis project implementation in the ER of a tertiary referral hospital.

The emergency room (ER) is the first gateway for patients with sepsis to inpatient units, and identifying best practices and benchmarks to be applied in this setting might crucially result in better patient's outcomes. In this study, we want to evaluate the results in terms of decreased the in-hospital mortality of patients with sepsis of a Sepsis Project developed in the ER. All patients admitted to the ER of our Hospital from the 1st January, 2016 to the 31stJuly 2019 with suspect of sepsis (MEWS score ≥ of 3) and positive blood culture upon ER admission were included in this retrospective observational study. The study comprises of two periods: Period A: From the 1st Jan 2016 to the 31st Dec 2017, before the implementation of the Sepsis project. Period B: From the 1st Jan 2018 to the 31stJul 2019, after the implementation of the Sepsis project. To analyze the difference in mortality between the two periods, a univariate and multivariate logistic regression was used. The risk of in-hospital mortality was expressed as an odds ratio (OR) and a 95% confidence interval (95% CI). Overall, 722 patients admitted in ER had positive BC on admissions, 408 in period A and 314 in period B. In-hospital mortality was 18.9% in period A and 12.7% in period B (p = 0.03). At multivariable analysis, mortality was still reduced in period B compared to period A (OR 0.64, 95% CI 0.41-0.98; p = 0.045). Having an infection due to GP bacteria or polymicrobial was associated with an increased risk of death, as it was having a neoplasm or diabetes. A marked reduction in in-hospital mortality of patients with documented BSI associated with signs or symptoms of sepsis after the implementation of a sepsis project based on the application of sepsis bundles in the ER.