A retrospective whole-genome sequencing analysis of carbapenem and colistin-resistant klebsiella pneumoniae nosocomial strains isolated during an MDR surveillance program

Multidrug-resistant Klebsiella pneumoniae (MDR Kp), in particular carbapenem-resistant Kp (CR-Kp), has become endemic in Italy, where alarming data have been reported on the spread of colistin-resistant CR-Kp (CRCR-Kp). During the period 2013–2014, 27 CRCR-Kp nosocomial strains were isolated within the Modena University Hospital Policlinico (MUHP) multidrug resistance surveillance program. We retrospectively investigated these isolates by whole-genome sequencing (WGS) analysis of the resistome, virulome, plasmid content, and core single nucleotide polymorphisms (cSNPs) in order to gain insights into their molecular epidemiology. The in silico WGS analysis of the resistome revealed the presence of genes, such as blaKPC, related to the phenotypically detected resistances to carbapenems. Concerning colistin resistance, the plasmidic genes mcr 1–9 were not detected, while known and new genetic variations in mgrB, phoQ, and pmrB were found. The virulome profile revealed the presence of type-3 fimbriae, capsular polysaccharide, and iron acquisition system genes. The detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), ColRNAI, IncX3, and IncFII(K) types. The cSNPs genotyping was consistent with the multi locus sequence typing (MLST) and with the distribution of mutations related to colistin resistance genes. In a nosocomial drug resistance surveillance program, WGS proved to be a useful tool for elucidating the spread dynamics of CRCR-Kp nosocomial strains and could help to limit their diffusion

Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: Retrospective cohort study

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation

Outcome variables in the evaluation of alcoholics' treatment: Lessons from the Italian Assessment of Alcoholism Treatment (ASSALT) project

The observational evaluation of alcoholics' treatments requires a combined analysis of alcoholic behaviour during treatment and of adherence to therapeutic programmes. The application of survival analysis techniques in this setting has been explored in this study. Two hundred and seventy alcoholics admitted to 15 Italian treatment units in a 1-year period were followed-up for 2 years, recording date and length of every recurrence episode and of definitive or transitory interruption of the planned treatment. An extensive use of several survival analysis techniques was made. The length of time between the start of the treatment and the first episode of relapse did not give a reliable measure of frequency of failures. Conversely, the length of time between the start of treatment and withdrawal appeared to be unbiased. The cumulative proportions of treatment-compliant patients (and the corresponding 95% confidence intervals) were 71% (66-76%), 63% (57-69%) and 53% (47-60%) after 6 months, 1 year and 2 years respectively from the start of treatment. Cumulative abstinence duration before withdrawal was significantly and positively associated with the risk of first, of definitive, and of every episode of treatment interruption. This first application of survival analysis techniques to the combined study of alcoholic behaviour and of adherence to treatment can improve our knowledge of treatment evaluation. Our results suggest that compliance to treatment is an objective and versatile outcome measure. Long-term follow-up studies aimed to elucidate the determinants of withdrawal should be performed

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality

Purpose: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Methods: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. Results: CMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010–1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993–0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223–5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852–8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757–1721, p = 0.528). Conclusion: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently