Association of piperacillin/tazobactam MIC and mortality in a cohort of ceftriaxone-resistant Escherichia coli bloodstream infections treated with piperacillin/tazobactam and carbapenems: a multicentric propensity score-weighted observational cohort study.

OBJECTIVES: To assess the impact of piperacillin/tazobactam MICs on in-hospital 30 day mortality in patients with third-generation cephalosporin-resistant Escherichia coli bloodstream infection treated with piperacillin/tazobactam, compared with those treated with carbapenems. METHODS: A multicentre retrospective cohort study was conducted in three large academic hospitals in Italy between 2018 and 2022. The study population comprised patients with monomicrobial third-generation cephalosporin-resistant E. coli bloodstream infection, who received either piperacillin/tazobactam or carbapenem therapy within 48 h of blood culture collection. The primary outcome was in-hospital 30 day all-cause mortality. A propensity score was used to estimate the likelihood of receiving empirical piperacillin/tazobactam treatment. Cox regression models were performed to ascertain risk factors independently associated with in-hospital 30 day mortality. RESULTS: Of the 412 consecutive patients included in the study, 51% received empirical therapy with piperacillin/tazobactam, while 49% received carbapenem therapy. In the propensity-adjusted multiple Cox model, the Pitt bacteraemia score [HR 1.38 (95% CI, 0.85-2.16)] and piperacillin/tazobactam MICs of 8 mg/L [HR 2.35 (95% CI, 1.35-3.95)] and ≥16 mg/L [HR 3.69 (95% CI, 1.86-6.91)] were significantly associated with increased in-hospital 30 day mortality, while the empirical use of piperacillin/tazobactam was not found to predict in-hospital 30 day mortality [HR 1.38 (95% CI, 0.85-2.16)]. CONCLUSIONS: Piperacillin/tazobactam use might not be associated with increased mortality in treating third-generation cephalosporin-resistant E. coli bloodstream infections when the MIC is <8 mg/L.

Incidence of bloodstream infections due to multidrug-resistant pathogens in ordinary wards and intensive care units before and during the COVID-19 pandemic: a real-life, retrospective observational study.

PURPOSE: SARS-COV-2 pandemic led to antibiotic overprescription and unprecedented stress on healthcare systems worldwide. Knowing the comparative incident risk of bloodstream infection due to multidrug-resistant pathogens in COVID ordinary wards and intensive care-units may give insights into the impact of COVID-19 on antimicrobial resistance. METHODS: Single-center observational data extracted from a computerized dataset were used to identify all patients who underwent blood cultures from January 1, 2018 to May 15, 2021. Pathogen-specific incidence rates were compared according to the time of admission, patient's COVID status and ward type. RESULTS: Among 14,884 patients for whom at least one blood culture was obtained, a total of 2534 were diagnosed with HA-BSI. Compared to both pre-pandemic and COVID-negative wards, HA-BSI due to S. aureus and Acinetobacter spp. (respectively 0.3 [95% CI 0.21-0.32] and 0.11 [0.08-0.16] new infections per 100 patient-days) showed significantly higher incidence rates, peaking in the COVID-ICU setting. Conversely, E. coli incident risk was 48% lower in COVID-positive vs COVID-negative settings (IRR 0.53 [0.34-0.77]). Among COVID + patients, 48% (n = 38/79) of S. aureus isolates were resistant to methicillin and 40% (n = 10/25) of K. pneumoniae isolates were resistant to carbapenems. CONCLUSIONS: The data presented here indicate that the spectrum of pathogens causing BSI in ordinary wards and intensive care units varied during the pandemic, with the greatest shift experienced by COVID-ICUs. Antimicrobial resistance of selected high-priority bacteria was high in COVID positive settings.

Impact of antimalarial resistance and COVID-19 pandemic on malaria care among pregnant women in Northern Uganda (ERASE): protocol of a prospective observational study.

BACKGROUND: Uganda accounts for 5% of all malaria cases and deaths reported globally and, in endemic countries, pregnancy is a risk factor for both acquisition of P. falciparum infection and development of severe malaria. In recent years, malaria control has been threatened by COVID-19 pandemic and by the emergence, in Northern Uganda, of both resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. METHODS: In this facility-based, prospective, observational study, pregnant women will be recruited at antenatal-care visits and followed-up until delivery. Collected data will explore the incidence of asymptomatic parasitemia and malaria-related outcomes, as well as the attitudes towards malaria prevention, administration of intermittent preventive treatment, healthcare seeking behavior and use of insecticide-treated nets. A subpopulation of women diagnosed with malaria will be recruited and their blood samples will be analyzed for detection of genetic markers of resistance to artemisinin derivatives and sulfadoxine-pyrimethamine. Also, to investigate the impact of COVID-19 on malaria care among pregnant women, a retrospective, interrupted-time series will be conducted on at the study sites for the period January 2018 to December 2021. DISCUSSION: The present study will explore the impact of COVID-19 pandemic on incidence of malaria and malaria-related adverse outcomes, along with the prevalence of resistance to artemisinin derivatives and to sulfadoxine-pyrimethamine. To our knowledge, this is the first study aiming to explore the combined effect of these factors on a cohort of pregnant women. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov public website on 26th April, 2022. CLINICALTRIALS: gov Identifier: NCT05348746.

Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study.

BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. METHODS: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. CONCLUSIONS: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Post-Prescription Audit Plus Beta-D-Glucan Assessment Decrease Echinocandin Use in People with Suspected Invasive Candidiasis.

Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing echinocandin use in persons with suspected invasive candidiasis. Materials and Methods: This is a prospective, pre-post quasi-experimental study of people starting echinocandins for suspected invasive candidiasis. The intervention of the study included review of each echinocandin prescription and discontinuation of treatment if a very low probability of fungal disease or a negative BDG value were found. Pre-intervention data were compared with the intervention phase. The primary outcome of the study was the duration of echinocandin therapy. Secondary outcomes were length of hospital stay and mortality. Results: Ninety-two echinocandin prescriptions were reviewed, 49 (53.3%) in the pre-intervention phase and 43 (46.7%) in the intervention phase. Discontinuation of antifungal therapy was possible in 21 of the 43 patients in the intervention phase (48.8%). The duration of echinocandin therapy was 7.4 (SD 4.7) in the pre-intervention phase, 4.1 days (SD 2.9) in persons undergoing the intervention, and 8.6 (SD 7.3) in persons in whom the intervention was not feasible (p at ANOVA = 0.016). Length of stay and mortality did not differ between pre-intervention and intervention phases. Conclusions: An intervention based on pre-prescription restriction and post-prescription audit when combined with BDG measurement is effective in optimizing antifungal therapy by significantly reducing excessive treatment duration.

Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients.

A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID-19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD-1 expression on both CD4+ T and CD8+ T cells in 42 COVID-19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen-activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID-19 infection.

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

BACKGROUND AND AIMS: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. METHODS AND RESULTS: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. CONCLUSIONS: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study.

Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain. Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics. Design: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score. Setting: Single academic medical center. Patients: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort). Intervention: FMT or antibiotics. Measurements: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days. Results: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group. Limitation: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort. Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI. Primary Funding Source: None.

Trimethoprim-sulfamethoxazole therapy for patients with carbapenemase-producing Klebsiella pneumoniae infections: retrospective single-center case series.

OBJECTIVE: The objective of the study was to evaluate the efficacy and tolerability of trimethoprim-sulfamethoxazole (also known as co-trimoxazole, TMPS) to treat Klebsiella pneumoniae (Kp)-K. pneumoniae carbapenemase (KPC) infections. METHODS: Clinical data of patients with a TMPS-susceptible Kp-KPC infection were collected as a case series. RESULTS: We report clinical outcomes and tolerability for 14 patients infected by Kp-KPC strains susceptible to TMPS, including three bloodstream infections. In ten cases (71.4%), TMPS was administered as monotherapy. In all but one case, Kp-KPC infection was cured. In the remaining patient, therapy was discontinued because of an adverse event. CONCLUSIONS: The use of TMPS to treat TMPS-susceptible Kp-KPC infections seems promising.

Impact of antibiotic stewardship on perioperative antimicrobial prophylaxis.

OBJECTIVE: Antibiotic prophylaxis (AP) is useful to prevent antimicrobial overuse, misuse and abuse, as well against the occurrence of surgical site infections (SSIs). This study aimed to describe the implementation of a quality improvement intervention on AP for elective surgery, as informal interviews showed a lower than expected compliance with internal recommendations, and to evaluate intervention's effect in terms of main drug consumption. DESIGN: A quality improvement intervention on all elective cases within 14 main surgical departments was performed. SQUIRE 2.0 guidelines were used in designing and reporting. SETTING: The intervention was implemented in an Italian Teaching Hospital 2 years after the adoption of internal evidence-based AP recommendations. PARTICIPANTS: Professionals involved in elective surgery. INTERVENTIONS: The intervention was structured into two phases: a survey was conducted during two non-consecutive weeks period (April-May 2013) to assess the adherence to the international guidelines in AP; survey's results were presented and discussed with all the surgical teams (December 2013-April 2014). MAIN OUTCOME MEASURES: Impact on cefazolin consumption (in defined daily doses per 100 procedures). RESULTS: Data of AP for 653 surgical procedures in terms of type, timing, duration, excess and defect were analyzed. An optimal AP rate resulted in 48.1% cases. Reduction in cefazolin use (-21.5%) and cost (-22.9%) was registered. CONCLUSIONS: Though results cannot be generalized to all hospital populations, the implemented intervention is likely to improve AP consequently improving quality of care and reducing costs. Further studies are needed to evaluate specific outcomes such as rate of SSIs and antibiotic resistance.

Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients.

BACKGROUND: Efavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption. METHODS: Patients starting any cART regimen including EFV + 2NRTIs or switching to EFV + 2NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model. RESULTS: Overall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, p < 0.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, p = 0.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, p = 0.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk. CONCLUSIONS: In our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.

Systemic Inflammation Response Index (SIRI) and Monocyte-to-Lymphocyte Ratio (MLR) Are Predictors of Good Outcomes in Surgical Treatment of Periprosthetic Joint Infections of Lower Limbs: A Single-Center Retrospective Analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA), whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR) and late infections with two-stage revision surgery. Two-stage revision is considered the "gold standard" for treatment of chronic prosthetic joint infection (PJI) as it enables local delivery of antibiotics, maintenance of limb-length and mobility, and easier reimplantation. Many studies have attempted to identify potential predicting factors for early diagnosis of PJI, but its management remains challenging. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. METHODS: A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation (EP) for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII, and AISI) were evaluated at the explantation time; at 4, 6, and 8 weeks after surgery; and at reimplantation time. The correlation between laboratory parameters and surgery success was evaluated and defined as infection absence/resolution at the last follow-up. RESULTS: A total of 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nine patients underwent DAIR revision surgery and chronic suppressive therapy; two patients died. Nineteen patients completed the two-stage revision process (prosthetic removal, spacer placement, and subsequent replanting). Among them, none showed signs of reinfection or persistence of infection at the last available follow-up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others (fewer in number) were submitted to resection arthroplasty and arthrodesis (Girdlestone technique) or chronic suppressive antibiotic therapy; the remaining were, over time, lost to follow-up. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7 and p-value 0.04) and MLR values (mean 0.4 SD 0.2 and p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation in the SIRI and PCR, also defined, respectively, as delta-SIRI (mean -2.3 SD 1.8 and p-value 0.03) and delta-PCR (mean -46 SD 35.7 and p-value 0.03), were associated with favorable outcomes. CONCLUSIONS: The results of our study suggest that, in patients with PJI undergoing EP, the SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of a favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant. More studies analyzing a wider cohort of patients with chronic PJI are needed to validate the promising results of this study.

Identification of two anti-Candida antibodies associated with the survival of patients with candidemia.

IMPORTANCE: Candidemia (bloodstream invasion by Candida species) is a major fungal disease in humans. Despite the recent progress in diagnosis and treatment, therapeutic options are limited and under threat of antimicrobial resistance. The disease mortality remains high (around 40%). In contrast with deep-seated invasive candidiasis, particularly that occurring in patients with hematologic malignancies and organ transplants, patients with candidemia are often not immunocompromised and therefore able to mount memory anticandidal immune responses, perhaps primed by Candida commensalism. We investigated antibody immunity in candidemia patients and report here on the ability of these patients to produce antibodies that react with Candida antigens. In particular, the patients with high titers of IgG reactive with two immunodominant, virulence-associated antigens (Als3 and MP65) had a higher 30-day survival. If confirmed by controlled, prospective clinical studies, our data could inform the development of antibody therapy to better treat a severe fungal infection such as candidiasis.

A Machine Learning Predictive Model of Bloodstream Infection in Hospitalized Patients.

The aim of the study was to build a machine learning-based predictive model to discriminate between hospitalized patients at low risk and high risk of bloodstream infection (BSI). A Data Mart including all patients hospitalized between January 2016 and December 2019 with suspected BSI was built. Multivariate logistic regression was applied to develop a clinically interpretable machine learning predictive model. The model was trained on 2016-2018 data and tested on 2019 data. A feature selection based on a univariate logistic regression first selected candidate predictors of BSI. A multivariate logistic regression with stepwise feature selection in five-fold cross-validation was applied to express the risk of BSI. A total of 5660 hospitalizations (4026 and 1634 in the training and the validation subsets, respectively) were included. Eleven predictors of BSI were identified. The performance of the model in terms of AUROC was 0.74. Based on the interquartile predicted risk score, 508 (31.1%) patients were defined as being at low risk, 776 (47.5%) at medium risk, and 350 (21.4%) at high risk of BSI. Of them, 14.2% (72/508), 30.8% (239/776), and 64% (224/350) had a BSI, respectively. The performance of the predictive model of BSI is promising. Computational infrastructure and machine learning models can help clinicians identify people at low risk for BSI, ultimately supporting an antibiotic stewardship approach.

Early assessment of blood culture negativity as a potential support tool for antimicrobial stewardship.

Objective: To assess whether 48-h negative blood culture (BC) bottles are still negative at the classic 120-h incubation endpoint and whether 48 h might be the time to make antimicrobial therapy decisions. Methods: Data from the first collected bottles from bloodstream infection (BSI) episodes of single patients were retrospectively analyzed. Probabilities of bottles being negative at the classic endpoint were calculated from 0 to 120 h of incubation. Results: Among BC-negative episodes (4018/4901 [82.0%]), most (2097/4018 (52.2%) occurred in medicine patients. At 48 h, probability was 100.0% (95% CI, 99.9-100.0) for all 4018 patients. Of these, 1244 (31.0%) patients remained on antibiotics until 120 h. Excluding 401 (32.2%) patients who received antibiotics for another (non-bloodstream) infection, 843 (67.8%) of 1244 patients could have merited early (48-h) discontinuation of antibiotics. Stopping treatment in these patients would have led to saving 5201 days of access (943 [18.1%] days), watch (3624 [69.7%] days), or reserve (634 [12.2%]) AWaRe groups' antibiotics, which correspond to 65.6% (5201/7928) of days of administered antibiotics in all 1244 patients. Conclusion: As an early indicator of BC negativity, the 48-h endpoint could reliably support antimicrobial stewardship, but the clinical judgment remains imperative especially when BSI is highly suspected.

Risk of SARS-CoV-2 infection in patients with hematologic diseases receiving tixagevimab/cilgavimab as pre-exposure prophylaxis in most recent Omicron sublineages era.

OBJECTIVES: Whether pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab 150 mg/150 mg (T/C) in individuals with hematologic disease (HD) may lead to a reduced risk of SARS-CoV-2 breakthrough infection (BTI)/hospitalization, or death in the Omicron era remains to be established. METHODS: An observational study included participants with HD who received PrEP. BTIs were defined as SARS-CoV-2 positivity by reverse transcription-polymerase chain reaction. The incidence of BTIs (95% CI) and of BTIs/hospitalization/death was calculated using the Kaplan-Meier method and as the number of BTIs per 100 person-years of follow-up according to the circulating variant of concern (VoC). A Poisson regression model was used to evaluate the association between the rate of incidence and circulating VoCs after controlling for demographics and clinical factors. RESULTS: We included 550 HD patients: 71% initiated T/C PrEP when BA.5 was the most prevalent, followed by XBB/EG, BA.2, and BA.1 (19%, 7%, and 3%, respectively). Overall, the 1-year incidence estimate of BTIs/hospitalization/death was 24% (18.7-29.4%). A greater risk of incident infections was observed when BA.5 and XBB/EG sub-lineages circulated (aRR 5.05 [2.17, 11.77]; P < .001 and 3.82 [1.50, 9.7]; P = 0.005, compared to BA.1, respectively). CONCLUSIONS: The 1-year incidence of SARS-CoV-2 BTIs/hospitalization/death was 24% which is in line with what was observed in other similar studies. The risk appeared to be higher when more recent Omicron sub-lineages were circulating suggesting a reduction of in vitro neutralization.

Vaccines and Myocardial Injury in Patients Hospitalized for COVID-19 Infection: the CardioCOVID-Gemelli Study.

BACKGROUND: Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown. OBJECTIVES: To assess the role of vaccines in modifying the risk of myocardial injury in COVID-19. METHODS: We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit). RESULTS: 1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury. CONCLUSIONS: In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.