Impact of Whole Genome Sequencing to investigate transmission of Serratia marcescens in Neonatal Intensive Care Unit.

Newborns admitted to neonatal intensive care units (NICU) are at increased risk of health care-associated infections. Serratia marcescens represent the third most common pathogen in NICU outbreaks. Here we present an outbreak investigation performed using Whole Genome Sequencing (WGS) analyses and the control measures implemented to limit the spread of S. marcescens in the NICU of an Italian hospital. In February 2023 S. marcescens was isolated from six newborns, when in 2022 this pathogen was isolated only from two samples in the same ward. Measures for infection prevention were adopted. Routinary surveillance screening, performed with rectal swabs collected at admission and weekly thereafter, was implemented to search for S. marcescens presence. Environmental samples were collected. All the isolates, obtained from the conjunctival swab of six newborns, from rectal swab of two newborns who did not develop infections, as well as from the aerators of two faucets, were sequenced. WGS analyses showed no correlation between the isolates from newborns and environmental isolates. The implementation of the measures for infection prevention and control had enabled us to successfully control the outbreak within a short period. WGS analyses proved to be crucial in outbreak investigation to limit the spreading of the pathogens.

Vaccination strategies for high-risk and fragile populations in Lombardy (Italy): a region-wide assessment of hospital-based models and best practices.

Background: Subjects with selected underlying medical conditions are at higher risk of infection and severe outcomes from vaccines preventable diseases. While most countries adopt life-course approaches to vaccination, high-risk group immunization programmes could maximize individual protection, while contributing to population health. The COVID-19 pandemic stimulated the planning and implementation of successful hospital-based high-risk groups' immunization models. However, in Italy, high-risk subjects' vaccine coverage is not actively monitored at the national or regional level, nor shared guidelines exist yet on hospital-based immunization programmes. Study Design: The study reports findings from a region-wide assessment of the availability, characteristics, and setting-specific features of hospital-based immunization programmes for high-risk subjects in the Lombardy region. Methods: Fondazione The Bridge a not-for-profit organization based in Milan, in collaboration with the Prevention Unit of the Lombardy Region Directorate for Welfare, and the University of Pavia coordinated a project aimed at bringing together regional health institutions, key stakeholders, academic experts, scientific societies and patients' associations to assess high-risk subjects' barriers to vaccine uptake and inform preventive programmes and policies. In this context, we designed and implemented a survey to systematically map the existence and characteristics of hospital-based immunization programmes targeting high-risk subjects. The survey was proposed to all 115 hospital medical directions of the Lombardy region. Results: We collected data from 97 hospital medical directions, with a response rate of 85%. Among respondents, 24% were publi-cly managed hospitals, 17% were Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) and 59% accredited private hospitals. Overall, 51.5% facilities in the Lombardy Region reported to actively administer vaccines to high-risk subjects in hospital settings, the prevalence being 89.6% in public hospitals. Among hospitals where vaccines are actively administered, 46% reported to have centralized vaccines ambulatory clinics, while 54% reported to administer vaccines in the context of inpa-tient care, within clinical wards. In 14% of hospitals vaccination counselling is carried out at the hospital level, while patients are referred to community services for the vaccine administration, 58% have established clinical pathways and formalized internal procedures to integrate vaccine prevention within the clinical care. Conclusions: Half of hospital facilities in the Lombardy Region administer vaccines to high-risk patients. Hospital-based im-munization models vary widely by vaccines programmes, organizational aspects, vaccines procurement and workforce involved. Identifying best practices and effective models can help tackle current challenges and improve immunization coverage for at-risk groups.

The immunogenicity and the safety of the adjuvanted glycoprotein E (gE)-based recombinant vaccine against herpes zoster (RZV) in cancer patients during immunotherapy.

Herpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response (p = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.

Outbreak of Candida parapsilosis fungemia in an intensive care unit during a COVID surge: an epidemic within a pandemic.

We sought to investigate epidemiology, risk factors, clinical features, and outcome of the C. parapsilosis blood stream infection (BSI) outbreaks observed during the first surges of COVID-19 pandemic in our population. Retrospective, monocentric observational study in the 24 bed intensive care unit (ICU) of a tertiary care medical center in northern Italy, from 2019 to 2021 first 5 months. 2030 patients were enrolled, of whom 239 were COVID-19 positive. The total incidence of Candida-BSI was 41.9 per 1000 admissions, with two outbreaks during 2020 spring and winter's COVID surges. The total numbers of C. parapsilosis BSI cases are 94, of which 21 during the first outbreak and 20 during the second. In our population, COVID-19 was strongly associated with C. parapsilosis BSI (OR 4.71, p < 0.001), as well as continuous renal replacement therapy (CRRT) (OR 3.44, p = 0.001), prolonged antibiotic therapy (OR 3.19, p = 0.004), and delayed infusion sets replacements (OR 2.76, p = 0.015). No statistically significant association was found between Candida-BSI episodes and mortality, when adjusted for other known outcome risk factors. COVID surges undermined the infectious control measures in our ICU, leading to two outbreak of C. parapsilosis BSI. A stricter, thorough management of intravascular devices and infusion set is crucial in prevention of catheter related BSI, and awareness must be kept high, especially in emergencies circumstances, such as the ongoing COVID-19 pandemic.

A Clinico-Pathological Multidisciplinary Team Increases the Efficacy of Skin Biopsy and Reduces Clinical Risk in Dermatology.

A clinical risk is an inherent risk in healthcare processes, including skin biopsy procedures, and may lead to misdiagnoses, increased healthcare costs and potential harm to patients. Indeed, clinical and histopathological data must be integrated if we are to reduce clinical risks and improve diagnostic accuracy in the diagnosis of dermatologic diseases. Although dermopathology services used to be part of a dermatologist's duty, the recent centralization of these laboratories has caused a loss of expertise and increased both complexity and safety issues. Some countries have implemented clinical-pathological correlation programs aimed at facilitating communication between clinicians and dermatopathologists. However, Italy has regulatory and cultural barriers that make the implementation of these programs difficult. Therefore, an internal analysis was carried out to assess the efficacy and impact that skin biopsy procedures for inflammatory and neoplastic conditions have on the quality of care in our dermatology department. As the analysis evidenced a high number of descriptive pathologic reports and discordant diagnoses, a multidisciplinary group of four dermatologists, four general pathologists and one dermatopathologist was set up. Herein, we present the results of this analysis and project and describe the structure of the multidisciplinary group. We also discuss the pros and cons, possibilities and limitations of our project, including the regulatory barriers of the Italian National Health System.

Five Level Triage vs. Four Level Triage in a Quaternary Emergency Department: National Analysis on Waiting Time, Validity, and Crowding-The CREONTE (Crowding and RE-Organization National TriagE) Study Group.

Background and Objectives: Triage systems help provide the right care at the right time for patients presenting to emergency departments (EDs). Triage systems are generally used to subdivide patients into three to five categories according to the system used, and their performance must be carefully monitored to ensure the best care for patients. Materials and Methods: We examined ED accesses in the context of 4-level (4LT) and 5-level triage systems (5LT), implemented from 1 January 2014 to 31 December 2020. This study assessed the effects of a 5LT on wait times and under-triage (UT) and over-triage (OT). We also examined how 5LT and 4LT systems reflected actual patient acuity by correlating triage codes with severity codes at discharge. Other outcomes included the impact of crowding indices and 5LT system function during the COVID-19 pandemic in the study populations. Results: We evaluated 423,257 ED presentations. Visits to the ED by more fragile and seriously ill individuals increased, with a progressive increase in crowding. The length of stay (LOS), exit block, boarding, and processing times increased, reflecting a net raise in throughput and output factors, with a consequent lengthening of wait times. The decreased UT trend was observed after implementing the 5LT system. Conversely, a slight rise in OT was reported, although this did not affect the medium-high-intensity care area. Conclusions: Introducing a 5LT improved ED performance and patient care.

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.

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.

The WEST Study: A Retrospective and Multicentric Study on the Impact of Steroid Therapy in West Nile Encephalitis.

Background: The use of steroid therapy in potentially life-threatening neuroinvasive forms of West Nile infection (WNND) is controversial. The aim of this study is to assess the efficacy of steroid therapy in reducing intrahospital mortality, length of stay, and neurological sequelae at discharge. Methods: This was a multicenter, retrospective, observational study conducted in 5 hospitals in Northern Italy, headed by the Fondazione IRCSS Policlinico San Matteo (Pavia). We extracted all patient data with WNND diagnoses, comparing patients who received steroid treatment with patients who did not receive steroid treatment between January 2014 and January 2022. Comparisons between the 2 groups were performed using chi-square tests for categorical variables and Mann-Whitney tests for non-normal continuous data, and a generalized linear model for the binomial family was carried out. Results: Data from 65 WNND patients were extracted. Among these patients, 33 (50.7%) received steroid therapy at any point during their hospitalization. Receiving steroid therapy did not significantly reduce intrahospital mortality (odds ratio [OR], 1.70; 95% CI, 0.3-13.8; P = .89) or neurological sequelae at discharge (OR, 0.53; 95% CI, 0.16-1.76; P = .47). Conclusions: Steroid treatment is currently used on a single-case basis in severe WNND. More prospective data are needed to demonstrate a protective effect on mortality and neurological sequelae.

Ventilator-Associated Pneumonia Due to MRSA vs. MSSA: What Should Guide Empiric Therapy?

The guidelines on ventilator-associated pneumonia (VAP) recommend an empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) according to its prevalence rate. Considering the MRSA and MSSA VAP prevalence over the last 9 years in our tertiary care hospital, we assessed the clinical value of the MRSA nasal-swab screening in either predicting or ruling out MRSA VAP. We extracted the data of 1461 patients with positive bronchoalveolar lavage (BAL). Regarding the MRSA nasal-swab screening, 170 patients were positive for MRSA or MSSA. Overall, MRSA had a high prevalence in our ICU. Despite the COVID-19 pandemic, there was a significant downward trend in MRSA prevalence, while MSSA remained steady over time. Having VAP due to MRSA did not have any impact on LOS and mortality. Finally, the MRSA nasal-swab testing demonstrated a very high negative predictive value for MRSA VAP. Our results suggested the potential value of a patient-centered approach to improve antibiotic stewardship.

Clinical Characteristics and Potential Risk Factors Associated with the SARS-CoV-2 Infection: Survey on a Health Care Workers (HCWs) Population in Northern Italy.

During the two years of the COVID-19 pandemic, more than 400 million cases all over the world have been identified. Health care workers were among the first to deal with this virus and consequently a high incidence of infection was reported in this population. The aim of the survey was to investigate health care workers' (HCWs) clinical characteristics and potential risk factors associated with the SARS-CoV-2 infection in a referral hospital in Northern Italy after the first and second waves of the pandemic. We administered a questionnaire during the flu vaccination campaign that took place at the end of 2020; among 1386 vaccinated HCWs, data was collected and analyzed for 1065 subjects. 182 HCWs (17%) declared that they had tested positive on at least a molecular or a serological test since the beginning of the pandemic. Comparing the infected vs. not infected HCWs, median age, BMI, smoking habit, presence of hypertension or other comorbidities were not significantly different, while having worked in a COVID ward was associated with the infection (ORadj = 1.54, 95% CI: 1.07-2.20). Respondents declared that more than 70% of contacts occurred in the hospital with patients or colleagues, while about 15% in domestic environments. Among the infected, the most reported symptoms were fever (62.1%), asthenia (60.3%), anosmia/ageusia (53.5%), arthralgia/myalgia (48.3%), headache or other neurological symptoms (46.6%), cough (43.1%) and flu-like syndrome (41.4%). The percentage of subjects who have been infected with SARS-CoV-2 seems to be higher in HCWs than in the general population; hence, in hospitals, protective measures and preventive strategies to avoid the spreading of the contagion remain crucial.

Characteristics and outcomes of vaccinated and nonvaccinated patients hospitalized in a single Italian hub for COVID-19 during the Delta and Omicron waves in Northern Italy.

OBJECTIVE: We compared the characteristics and outcomes of vaccinated and nonvaccinated patients hospitalized with COVID-19. DESIGN: We analyzed patients hospitalized in a COVID hub during three one-month periods: (i) October 15, 2020-November 15, 2020 (prevaccination peak); (ii) October 15, 2021-November 15, 2021 (Delta wave); (iii) December 15, 2021-January 15, 2022 (Omicron wave). To define the epidemiologic context, SARS-CoV-2 infection in healthcare workers was analyzed. RESULTS: SARS-CoV-2 infection incidence in healthcare workers was 146 cases per 1000 persons in 2020 (prevaccination) and 67 in 2021 (postvaccination, when the Omicron variant caused most infections). There were 420 hospitalized patients in the prevaccination period, 51 during the Delta wave (52.1% vaccinated) and 165 during the Omicron wave (52.9% vaccinated). During the Delta wave, a significantly higher number of nonvaccinated (29.2%) than vaccinated patients (3.7%) were admitted to the intensive care unit (ICU) (p = 0.019). Nonvaccinated patients were younger and had a lower rate of concomitant medical conditions (53.2% vs 83.7%; p < 0.001) during the Omicron wave when 80% of patients admitted to ICU and all those who died were still infected by the Delta variant. CONCLUSIONS: Vaccine effectiveness in fragile individuals appears to be lower because of a faster immunity decline. However, the Omicron variant seems to cause less severe COVID-19.

Mortality due to COVID-19 during the pandemic: A comparison of first, secondo and third SMAtteo COvid19 REgistry (SMACORE).

COVID-19 tide had shattered on European countries with three distinct and tough waves, from March and April, 2020; October and November, 2020 and March and April, 2021 respectively. We observed a 50% reduction in the hazard of death during both wave II and III compared with wave I (HR 0.54, 95%CI 0.39-0.74 and HR 0.57, 95%CI 0.41-0.80, respectively). Sex and age were independent predictors of death. We compare in-hospital mortality of COVID-19 patients admitted at our Referral Hospital of Northern Italy during the different waves, discuss the reasons of the observed differences and suggest approaches to the challenges ahead.

SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers.

Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58-93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p = 0.01). All analyzed patients, in whom the amount of viral RNA was sufficient for genome sequencing, results infected by the alpha variant. Antibody and T-cell responses are not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, is observed in two (6.1%) cases. This real-world data support the protective effect of BNT162b2 vaccine. A triple antigenic exposure, such as two-dose vaccine schedule in experienced subjects, may confer a higher protection.

Impact of Coronavirus Disease 2019 Pandemic on Crowding: A Call to Action for Effective Solutions to "Access Block".

INTRODUCTION: Healthcare patterns change during disease outbreaks and pandemics. Identification of modified patterns is important for future preparedness and response. Emergency department (ED) crowding can occur because of the volume of patients waiting to be seen, which results in delays in patient assessment or treatment and impediments to leaving the ED once treatment is complete. Therefore, ED crowding has become a growing problem worldwide and represents a serious barrier to healthcare operations. METHODS: This observational study was based on a retrospective review of the epidemiologic and clinical records of patients who presented to the Foundation IRCCS Policlinic San Matteo in Pavia, Italy, during the coronavirus disease 2019 (COVID-19) outbreak (February 21-May 1, 2020, pandemic group). The methods involved an estimation of the changes in epidemiologic and clinical data from the annual baseline data after the start of the COVID-19 pandemic. RESULTS: We identified reduced ED visits (180 per day in the control period vs 96 per day in the pandemic period; P < 0.001) during the COVID-19 pandemic, irrespective of age and gender, especially for low-acuity conditions. However, patients who did present to the ED were more likely to be hemodynamically unstable, exhibit abnormal vital signs, and more frequently required high-intensity care and hospitalization. During the pandemic, ED crowding dramatically increased primarily because of an increased number of visits by patients with high-acuity conditions, changes in patient management that prolonged length of stay, and increased rates of boarding, which led to the inability of patients to gain access to appropriate hospital beds within a reasonable amount of time. During the pandemic, all crowding output indices increased, especially the rates of boarding (36% vs 57%; P < 0.001), "access block" (24% vs 47%; P < 0.001), mean boarding time (640 vs 1,150 minutes [min]; P 0.001), mean "access block" time (718 vs 1,223 min; P < 0.001), and "access block" total time (650,379 vs 1,359,172 min; P < 0.001). CONCLUSION: Crowding in the ED during the COVID-19 pandemic was due to the inability to access hospital beds. Therefore, solutions to this lack of access are required to prevent a recurrence of crowding due to a new viral wave or epidemic.