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Background: Recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) with resistance to ceftazidime/avibactam (CZA-R) has been described, including KPC variants that restore carbapenem susceptibility. The aim of the study was to analyze the clinical characteristics and outcomes of infections caused by CZA-R KPC-Kp., Methods: From 2019 to 2021, a retrospective 2-center study including patients with infections due to CZA-R KPC-Kp hospitalized at 2 academic hospitals in Rome was conducted. Demographic and clinical characteristics were collected. Principal outcome was 30-day all-cause mortality. Statistical analyses were performed with Stata-IC17 software., Results: Overall, 59 patients were included (mean age, 64.4 ± 14.6 years; mean Charlson comorbidity index score, 4.5 ± 2.7). Thirty-four patients (57.6%) had infections caused by CZA-R and meropenem (MEM)-susceptible strains. A previous CZA therapy was observed in 40 patients (67.8%), mostly in patients with MEM-susceptible KPC variant (79.4% vs 52%, P = .026). Primary bacteremia was observed in 28.8%, followed by urinary tract infections and pneumonia. At infection onset, septic shock was present in 15 subjects (25.4%). After adjustment for confounders, only the presence of septic shock was independently associated with mortality ( P = .006)., Conclusions: Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to MEM. Nevertheless, one-third of patients had never received CZA before KPC-Kp CZA-R. Since the major driver for mortality was infection severity, understanding the optimal therapy in patients with KPC-Kp CZA-R infections is of crucial importance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Since the beginning of 2020, the SARS-CoV-2 pandemic has become a serious public health problem. Numerous studies have highlighted the main clinical features of COVID-19, mainly the huge heterogeneity of the clinical manifestations that can vary from asymptomatic infection to serious viral pneumonia with a high mortality rate. The aim of this study was to analyze retrospectively the clinical characteristics and assess the risk factors for mortality in an Italian cohort of patients with COVID-19., Methods: Retrospective analysis including patients with COVID-19 admitted to the Infectious Diseases wards of Azienda Ospedaliera Universitaria Policlinico "Umberto 1", Rome, from March 2020 to May 2020. The data were part of an electronic anonymous web-based database processed by SIMIT (Italian Society of Infectious and Tropical Diseases)., Results: 258 patients were included in the analysis, and 34 (13.2%) died. The median age was 62 (IQR, 52-74), 106 (40%) were women, and 152 (60%) were males, 172 (66.7%) had at least one co-morbidity. The most common signs and symptoms were: fever [221 (85.6%)], cough [135 (52.3%)], and dyspnea [133 (51.5%)]. The PaO2/FiO2 ratio was often altered [352 (IQR, 308-424)]. Lymphopenia [lymphocyte counts, 875/μL (IQR, 640-1250)] and high levels of D-dimer [mg/dL, 874 (IQR, 484-1518)] were found. Non-survivors were older than survivors [median age, 74 (IQR, 67-85)] vs. 61 (QR, 51-72)], mostly men [25 (73.5%)] and more frequently with more than 2 comorbidities [21 (61.8%) vs. 94 (42.1%)]. In the multiple logistic regression model, the variables associated with in-hospital mortality were age [OR, 3.65 (95% CI, 1.22-10.89)], male gender [OR, 2.99 (95% CI, 1.18-7.54)], blood urea [OR, 2.76 (95% CI, 1.20-6.35)] and a low PaO2/FiO2 ratio [OR, 0.28 (95% CI, 0.12-0.62)]., Conclusion: The mortality rate in COVID-19 was 13,2%. The risk factors associated with in-hospital mortality were advanced age, male sex, increased blood urea, and the PaO2/FiO2 ratio reduction.

Background: Remdesivir (REM) has shown potent antiviral activity in vitro and efficacy in animal models of COVID-19; nevertheless, clinical trials and real-life reports have shown conflicting data on its effectiveness. Aims of the study were to evaluate the impact of remdesivir on I) Intensive Care Unit (ICU) admission, II) need for orotracheal intubation (OTI) and III) in-hospital mortality. Furthermore, we estimated the kinetics of laboratory parameters and assessed the risk factors for in-hospital mortality in the remdesivir population., Methods: We conducted a retrospective, single-center, case-control (1:1) study including hospitalized patients with confirmed SARS-CoV-2 infection. Cases were patients treated with remdesivir for 5 days, controls were patients not receiving remdesivir., Results: A total of 192 patients (96 cases and 96 controls) were included in the study. Patients receiving remdesivir had a lower rate of ICU admission and need for OTI than controls, whereas no difference between cases and controls were observed as for mortality rate. However, at multivariable analysis remdesivir was not associated with ICU admission neither with OTI. Instead, presence of haematological malignancies, lower duration of symptoms, higher severity of infection and low lymphocytes count at admission were independently associated with in-hospital mortality. In patients treated with remdesivir a low albumin value and duration of lymphopenia were significantly associated with mortality., Conclusions: Our real-life study showed that therapy with remdesivir did not have impact on either ICU admission, need for OTI or in-hospital mortality., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest., (Copyright © 2016 - 2022 InfezMed.)

Background: Electrocardiogram (ECG) offers a valuable resource easily available in the emergency setting. Objective: Aim of the study was to describe ECG alterations on emergency department (ED) presentation or that developed during hospitalization in SARS-CoV-2-infected patients and their association with 28-day mortality. Methods: A retrospective, single-center study including hospitalized patients with SARS-CoV-2 was conducted. ECG was recorded on ED admission to determine: heart rhythm, rate, and cycle; atrio-ventricular and intra-ventricular conduction; right ventricular strain; and ventricular repolarization. A specialized cardiologist blinded for the outcomes performed all 12-lead ECG analyses and their interpretation. Results: 190 patients were included, with a total of 24 deaths (12.6%). Age (p < 0.0001) and comorbidity burden were significantly higher in non-survivors (p < 0.0001). Atrial fibrillation (AF) was more frequent in non-survivors (p < 0.0001), alongside a longer QTc interval (p = 0.0002), a lower Tp-e/QTc ratio (p = 0.0003), and right ventricular strain (p = 0.013). Remdesivir administration was associated with bradycardia development (p = 0.0005) but no increase in mortality rates. In a Cox regression model, AF (aHR 3.02 (95% CI 1.03−8.81); p = 0.042), QTc interval above 451 ms (aHR 3.24 (95% CI 1.09−9.62); p = 0.033), and right ventricular strain (aHR 2.94 (95% CI 1.01−8.55); p = 0.047) were associated with higher 28-day mortality risk. Conclusions: QTc interval > 451 ms, right ventricular strain, and AF are associated with higher mortality risk in SARS-CoV-2 hospitalized patients. ECG recording and its appropriate analysis offers a simple, quick, non-expensive, and validated approach in the emergency setting to guide COVID-19 patients’ stratification.

Convalescent plasma (CP) therapy might be effective in patients with haematological malignanciesand B-cell depletion. We report a single-centre experience of COVID-19 patients with non-Hodgkinlymphoma and absence of B-cells as a consequence of anti-CD20 therapy successfully treated withCP from October 2020 to May 2021. CP was given in the presence of pneumonia with respiratoryfailure despite standard treatment and consisted of three infusions on an alternate-day basis. A reviewof the current literature on this topic was also performed. Six patients were identified (medianage 59.5 years (range 50-73)). The last anti-CD20 drug administration occurred 60 days before infection(range 0-360). CP was administered after a median of 51 days (range 9-120) from SARS-CoV-2diagnosis, with an early improvement in all but one subject. We suggest a possible clinical benefitof convalescent CP treatment in COVID-19 patients with haematological malignancies and B-celldepletion having persistent/recurrent pneumonia.

Background: NK cells seem to be mainly involved in COVID-19 pneumonia. Little is known about NKT cells which represent a bridge between innate and adaptive immunity., Methods: We characterized peripheral blood T, NK and NKT cells in 45 patients with COVID-19 pneumonia (COVID-19 subjects) and 19 healthy donors (HDs). According to the severity of the disease, we stratified COVID-19 subjects into severe and non-severe groups., Results: Compared to HDs, COVID-19 subjects showed higher percentages of NK CD57+ and CD56dim NK cells and lower percentages of NKT and CD56bright cells. In the severe group we found a significantly lower percentage of NKT cells. In a multiple logistic regression analysis, NKT cell was independently associated with the severity of the disease., Conclusions: The low percentage of NKT cells in peripheral blood of COVID-19 subjects and the independent association with the severity of the disease suggests a potential role of this subset., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Drug-induced aseptic meningitis (DIAM) represents a diagnostic challenge since clinical and cerebrospinal fluid (CSF) findings may be indistinguishable from a bacterial meningitis. Intravenous immunoglobulin (IVIg) are commonly used in a variety of diseases, including inflammatory and autoimmune disorders. Although usually well-tolerated, various adverse effects have been reported. DIAM is a serious neurological side effect of IVIg therapy: albeit rare (0.067% of all IVIg infusions), the condition represents an important diagnostic challenge and should be considered by physicians. Here we report a case of an aseptic meningitis induced by IVIg therapy in a child with acute Epstein-Barr virus (EBV) infection and thrombocytopenia.

The new QuantiFERON-TB Gold Plus employs modified peptides optimized to elicit an IFNγ response from CD8 + cytotoxic T lymphocytes in addition to CD4 + T cells. With a view to improve the difficult identification of TB cases, we assessed the combination of two specific immunological markers comprising IFNγ secretion and T cells co-expression of CD25 and CD134 in response to Mycobacterium tuberculosis-specific antigens. A total of 34 subjects with suspected TB and 10 age-matched HD were prospectively enrolled. Assessing the performance of QFT-Plus in terms of the TB1 and TB2 results, we found that in TB patients, the quantitative IFNγ value in TB2 was similar to that in TB1, and we did not find any differences irrespective of the disease (pulmonary or extra-pulmonary). The flow cytometric CD25/CD134 assay, allowed a more accurate differentiation between M. tuberculosis-infected and uninfected patients, with a better combination of sensitivity and specificity, especially by evaluation of CD4 + T-cell subset. All individuals with negative QFT-Plus results displayed a positive CD25/CD134 response. Overall, a positive correlation was found between T cells co-expressing CD25/CD134 and IFNγ levels in response to both QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes. We demonstrated that both TB1 and TB2 induce a higher expression of CD25 + CD134 + markers on CD4 + T cells among infected TB subjects, compared to the lower degree of CD8 + T cells, mainly induced to TB2 stimulation. We suggest that a combined use of classic QFT-Plus and specific CD25/CD134 response may be a useful means in the diagnostic workup for active TB.