Clinical characteristics and outcome of ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae infections. A retrospective, observational, 2-center clinical study

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 & PLUSMN; 14.6 years; mean Charlson comorbidity index score, 4.5 & PLUSMN; 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.Clinical characteristics and outcomes of infections caused by ceftazidime/avibactam-resistant (CZA-R) Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae were analyzed. Ceftazidime/avibactam-resistant and meropenem-susceptible KPC variants accounted for more than half of patients. Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to meropenem. Nevertheless, one-third of patients had never received CZA before isolation of CZA strains. Infection severity was the only independent predictor of 30-day mortality

Prognostic Value of 12-Leads Electrocardiogram at Emergency Department in Hospitalized Patients with Coronavirus Disease-19

BackgroundElectrocardiogram (ECG) offers a valuable resource easily available in the emergency setting.ObjectiveAim 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.MethodsA 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.Results190 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.ConclusionsQTc 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 for haematological patients with SARS-CoV-2 pneumonia and severe depletion of B-cell lymphocytes following anti-CD20 therapy: a single-centre experience and review of the literature

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

Diagnostic performance in active TB of QFT-Plus assay and co-expression of CD25/CD134 in response to new antigens of Mycobacterium tuberculosis

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

Real-life use of remdesivir-containing regimens in COVID-19: a retrospective case-control study

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