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.

The experience of the health care workers of a severely hit SARS-CoV-2 referral Hospital in Italy: incidence, clinical course and modifiable risk factors for COVID-19 infection.

BACKGROUND: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running a high risk of being infected by the SARS-CoV-2 virus.Since limiting transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in health care setting is crucial to avoid the community spread of SARS-CoV-2, we want to share our experience as an early hit hospital where standard infection control practices have been conscientiously applied and effective. We believe that our example, as first and hardest hit country, might be a warning and aid not only for those who have been hit later, but also for a second fearful wave of contagion. In addition, we want to offer an insight on modifiable risk factors for HWs-related infection. METHODS: Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs, which underwent a nasopharyngeal swab for SARS-CoV-2, were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. RESULTS: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33% (9.72-13.21). Working in a COVID-19 ward, being a former smoker (versus being a person who never smoked) and BMI was positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. CONCLUSIONS: Assuming an equal accessibility and proper use of personal protective equipment of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing.

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.

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.

Association between Vitamin D Serum Levels and Immune Response to the BNT162b2 Vaccine for SARS-CoV-2.

The use of micronutrients such as vitamin D could improve the response to viral vaccines, particularly in immunosuppressed and immunosenescent subjects. Here, we analysed the association between serum 25-hydroxyvitamin D (25OHD) levels and the immune response elicited by the BNT162b2 vaccine in a cohort of 101 healthcare workers naïve for SARS-CoV-2 infection. We observed no significant differences in anti-spike (S) IgG and T-cell responses according to the 25OHD status at baseline. However, significant correlations between the 25OHD concentration at baseline and (i) the anti-S response (p < 0.020) and (ii) the neutralizing antibody (NT) titre (p = 0.040) at six months after the second dose were detected. We concluded that adequate levels of vitamin D may improve the immune response to mRNA vaccines such as BNT162b2, and that further larger studies are warranted in order to confirm these preliminary observations.

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.

Incidence of SARS-CoV-2 infection in health care workers from Northern Italy based on antibody status: immune protection from secondary infection- A retrospective observational case-controlled study.

OBJECTIVE: The protection from SARS-CoV-2 infection induced by SARS-CoV-2 anti-S1 and anti-S2 IgG antibody positivity resulting from natural infection was evaluated. METHODS: The frequency of SARS-CoV-2 infection (as determined by virus RNA detection) was evaluated in a group of 1,460 seropositive and a control group of 8,150 seronegative healthcare workers in three Centres of Northern Italy in the period June-November 2020. Neutralizing serum titers were analyzed in seropositive subjects with or without secondary SARS-CoV-2 infection. RESULTS: During the 6-month survey, 1.78% seropositive subjects developed secondary SARS-CoV-2 infection while 6.63% seronegative controls developed primary infection (odds ratio: 0.26; 95% confidence interval: 0.17-0.38). Secondary infection was associated with low or absent serum neutralizing titer (p<0.01) and was mildly symptomatic in 45.8% cases vs 71.4% symptomatic primary infections (odds ratio: 0.34; 95% confidence interval: 0.16-0.78). CONCLUSIONS: Immunity from natural infection appears protective from secondary infection; therefore, vaccination of seronegative subjects might be prioritized.

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.

Preparing for the Maximum Emergency with a Simulation: A Table-Top Test to Evaluate Bed Surge Capacity and Staff Compliance with Training.

INTRODUCTION: The sudden increase in the number of critically ill patients following a disaster can be overwhelming. STUDY OBJECTIVE: The main objective of this study was to assess the real number of available and readily freeable beds ("bed surge capacity") and the availability of emergency operating rooms (OR) in a maximum emergency using a theoretical simulation. PATIENTS AND METHODS: The proportion of dismissible patients in four areas (Medical Area, Surgical Area, Sub-intensive Care Units, Intensive Care Units) and three emergency OR was assessed at 2 and 24 hours after a simulated maximum emergency. Four scenarios were modeled. Hospitalization and surgical capacities were assessed on weekdays and holidays. The creation of new beds was presumed by the possibility of moving patients to a lower level of care than that provided at the time of detection, of dislocation of patients to a discharge room, with care transferred to lower-intensity hospitals, rehabilitation, or discharge facilities. The Phase 1 table-top simulations were conducted during the weekday morning hours. In particular, the 24-hour table-top simulations of a hypothetical event lasted about 150 minutes compared to those conducted at 2 hours, which were found to be longer (about 195 minutes). Phase 2 was conducted on two public holidays and a quick response time was observed within the first 40 minutes of the start of the test (about 45% of departments). RESULTS: The availability of simulated beds was greater than that indicated in the maximum emergency plans (which was based solely on the census of beds). Patients admitted to Intensive Care and The Sub-Intensive Area may be more difficult to move than those in low-intensity care. The availability of emergency OR was not problematic. Age influenced the possibility of remitting/transferring patients. CONCLUSION: Simulation in advance of a maximum emergency is helpful in designing an efficient response plan.

A Multidimensional Approach of Surgical Mortality Assessment and Stratification (Smatt Score).

Surgical mortality is the most significant measure of outcome in surgical healthcare. The objective was to assess surgical 30 days mortality and improve the identification of predictors for personalized risk stratification of patients undergoing elective and emergency surgery. The study was conducted as a single-center cohort retrospective observational study, based on the analysis of data collected from patients surgically treated from 2002 to 2014 in a multi-disciplinary research and care referral hospital with global case mix of 1.27. The overall in-hospital mortality rate was 1.89% (95% CI 1.82-1.95). In the univariable analysis, numerous predictors were significantly associated with in-hospital death following surgery. In the multivariable model, age, BMI (Body Mass Index), ASA score, department, planned surgical complexity, surgical priority, previous surgeries in the same hospitalization, cardiovascular, pulmonary, hepato-renal comorbidities, drug intolerance, cancer and AIDS were independently associated with mortality after surgery. At logistic regression, the computed SMATT score (graded 0-100), generated on the basis of multivariate analysis, demonstrated a good discrimination (10-fold cross-validated AUC-ROC 0.945, 95%CI 0.941-0.948) and correctly classified 98.5% of those admissions with a probability of death >50%. The novel SMATT score, based on individual preoperative and surgical factors, accurately predicts mortality and provides dynamic information of the risk in redo/reoperative surgery.

Timely adaptation of a Pediatric Unit to COVID-19 emergency in Northern Italy: the experience of Fondazione IRCCS Policlinico San Matteo in Pavia.

Italy is one of the most exposed countries worldwide to COVID-19, and Lombardy is the most affected region in Italy. In this context, Fondazione IRCCS Policlinico San Matteo in Pavia, one of the largest University hospitals in the region, has been involved in the management of the outbreak since its inception. Immediately after the communication of the first Italian COVID-19+ patient, the Pediatric Unit has been completely reorganized to face the approaching outbreak. The optimization of the Pediatric Unit resources for COVID-19 emergency is reported as an example to safely preserve health activity during the pandemic.

Emergency Department and Out-of-Hospital Emergency System (112-AREU 118) integrated response to Coronavirus Disease 2019 in a Northern Italy centre.

Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating "out-of-hospital" and "hospital" activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The "out-of-hospital" response was analysed in terms of calls, rescues and missions, whereas the "hospital" response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5 weeks of the Covid-19 outbreak (February 21-March 26, 2020) were compared with a reference time window referring to the previous 5 weeks (January 17-February 20, 2020) and with the corresponding historical average data from the previous 5 years (February 21-March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+ 440%). After 5 weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+ 48% and + 10%, respectively) and the historical control (+ 53% and + 22%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants, + 108%). To minimize the possibility of intra-hospital spreading of the infection, a separate "Emergency Department-Infective Disease" was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n = 720) were admitted in general wards (n = 629) or intensive care unit (n = 91). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the "out-of-hospital" and "in-hospital" systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future.

Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy.

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to April 28th 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48-69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.

Vaccination coverage and mortality after splenectomy: results from an Italian single-centre study.

Splenectomy is a well-recognised risk factor for life-threatening overwhelming post-splenectomy infection (OPSI). To prevent OPSI, immunisations against encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae) and influenza virus are recommended. However, there is still a lack of uniformity and poor compliance with these recommendations. Following a local physicians' awareness campaign regarding the importance of vaccine prophylaxis of splenectomised patients, we aimed to register vaccination coverage, mortality and infection rates in all patients who underwent splenectomy at our hospital, over a six-year time span. Reasons for splenectomy, patients' compliance with vaccinations, mortality and infectious events were recorded. The reasons for splenectomy in the 216 identified patients (mean age 58.2 ± 14; M:F ratio 1.4:1) were haematologic disorders (38.8%), solid tumours (28.7%), traumatic rupture (22.7%) and other causes (9.7%). A total of 146 patients (67.6%) received at least one of the four vaccines. Overall, the mortality rate was significantly greater in unvaccinated compared to vaccinated patients (p < 0.001), although after the adjustment for the cause of splenectomy the statistical significance was lost (p = 0.085) due to the burden of solid tumour-related mortality. Among the 21 reported cases of OPSI, eight were fatal and five were potentially vaccine-preventable. Our results show that two-thirds of splenectomised patients comply with vaccine prophylaxis. Future interventional studies or ad hoc registries might overcome barriers to vaccination or intentional non-compliance.