Background
Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.
Methods
A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.
Results
In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.
Conclusions
Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.
Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
Yersinia enterocolitica is an unusual cause of septicaemia, usually occurring in immunocompromised hosts. Endocardial involvement is rare and generally presents as acute endocarditis. We describe the case of a 73-y-old woman, apparently without risk factors for endocarditis, admitted to hospital for persistent fever of unknown origin, arthralgia, and weight loss. Y. enterocolitica was isolated from blood and urine cultures, and echocardiography showed a pedunculated vegetation attached to the non-coronary cusp of the aortic valve. Symptoms and fever resolved after 3 days of intravenous cefotaxime plus amikacin, which were continued for the 2 weeks of her hospital stay; this treatment was followed by intravenous ceftriaxone after discharge. We hypothesized that a chemotherapy course administered 2 months previously for breast cancer might have been a predisposing factor for the Y. enterocolitica valvular infection and that immune system recovery contributed to mitigate the clinical presentation as subacute endocarditis.
Both the virtual phenotype and rule-based interpretation methods of HIV genotyping can guide the selection of effective antiretroviral drugs for a salvage regimen.
Un anno di sorveglianza microbiologica nel reparto di terapia intensiva dell'Ospedale S. Biagio di Domodossola (VB) ASL 14 SUMMARY Microbiological surveillance in Intensive Care Unit (ICU) is essential not only for empirical antimicrobial therapy, but also for epidemiological suggestion. We describe one year observation (2006) of microbiological samples, especially bronchial samples, in a polivalent ICU in San Biagio Hospital (Domodossola ASL 14 Piemonte) where systematic culture of sputum (surveillance cultures) was routinely performed. During this period, 208 bronchial samples were collected and cultured.Among these, 56 (27%) resulted positive for bacteria. Gram positive were isolated in 31% of cases (the most frequent being Staphylococcus aureus), whereas Gram negative in the remaining 69% (especially Pseudomonas aeruginosa and Escherichia coli). The antibiotic resistance to oxacillin was found in 50% of staphylococcal strains. Pseudomonas was susceptible to aminoglycosides, carbapenems and cefepime; all strains were ß lactamase producer. The tabular of dose defining day for the same year demonstrates that penicillin with β lactamase inhibitor is the most employed in our ICU (DDD 36%). This paper confirmed that systematic culture is important to get informations for epidemiology, antimicrobial strategies and control of multidrug resistant clusters.
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