Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Influence of vegetable diets on physiological and immune responses to thermal stress in Senegalese sole (Solea senegalensis).

The substitution of fish resources as ingredients for aquafeeds by those based on vegetable sources is needed to ensure aquaculture sustainability in the future. It is known that Senegalese sole (Solea senegalensis) accepts high dietary content of plant ingredients without altering growth or flesh quality parameters. However, scarce information is available regarding the long-term impact of vegetable diets (combining the inclusion of both vegetable protein and oils) on the stress response and immunity of this fish species. This study aims to evaluate the concomitant effect of the extended use of vegetable protein-based diets with fish oil (FO) replacement (0, 50 or 100%) by vegetable oils (VO), on the response to acute (10 min) or prolonged (4 days) stress, induced by thermal shock. Plasma levels of cortisol, glucose and lactate as well as hepatic levels of glucose, glycogen and lactate were evaluated as primary and secondary responses to stress, 6 and 18 months after feeding the experimental diets (6 and 18 MAF). The brain monoaminergic activity in telencephalon and hypothalamus, and non-specific immune parameters were also evaluated. As expected, thermal shock induced an increase in values of plasma parameters related to stress, which was more evident in acute than in prolonged stress. Stress also affected lactate levels in the liver and the values of the alternative complement pathway-ACH50 in the plasma. Dietary substitution of FO induced an effect per se on some parameters such as decreased hepatic glucose and glycogen levels and peroxidase activity in plasma as well enhanced serotonergic activity in brain of non-stressed fish. The results obtained in some parameters indicate that there is an interaction between the use of vegetable diets with the physiological response to thermal stress, as is the case of the hepatic lactate, serotonergic neurotransmission in brain, and the activity of ACH50 in plasma. These results suggest that the inclusion of VO in plant protein based diets point to a slightly inhibited stress response, more evident for an acute than a prolonged stress.

Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV-infected patients: a multicenter study of 67 cases.

OBJECTIVE: To assess the clinical characteristics and the factors that influenced the prognosis of patients with HIV and infection caused by Rhodococcus equi. DESIGN: Observational, multicenter study in 29 Spanish general hospitals. SETTING: These hospitals comprised a total of 20,250 beds for acute patients and served a population of 9,716,880 inhabitants. PATIENTS: All patients with HIV and diagnosed R equi infection until September 1998. RESULTS: During the study period, 19,374 cases of AIDS were diagnosed. Sixty-seven patients were included (55 male patients; mean +/- SD age, 31.7 +/- 5.8 years). At the time of diagnosis of R equi infection, the mean CD4+ lymphocyte count was 35/ micro L (range, 1 to 183/ micro L) and the stage of HIV infection was A3 in 10.4% of patients, B3 in 31.3%, C3 in 56.7%, and unknown in 1.5%. R equi was most commonly isolated in sputum (52.2%), blood cultures (50.7%), and samples from bronchoscopy (31.3%). Chest radiographic findings were abnormal in 65 patients (97%). Infiltrates were observed in all of them, with cavitations in 45 patients. The most active antibiotics against the strains isolated were vancomycin, amikacin, rifampicin, imipenem, ciprofloxacin, and erythromycin. After a mean follow-up of 10.7 +/- 12.8 months, 23 patients (34.3%) died due to causes related to R equi infection and 6 other patients showed evidence of progression of the infection. The absence of highly active antiretroviral therapy (HAART) was independently associated with mortality related to R equi infection (relative risk, 53.4; 95% confidence interval, 1.7 to 1,699). Survival of patients treated with HAART was much higher than that of patients who did not receive this therapy. CONCLUSIONS: Infection by R equi is an infrequent, opportunistic complication of HIV infection and occurs during advanced stages of immunodepression. In these patients, it leads to a severe illness that usually causes a bacteremic, cavitary pneumonia, although HAART can improve the prognosis.

Effect of penicillin resistance of Streptococcus pneumoniae on the presentation, prognosis, and treatment of pneumococcal endocarditis in adults.

We performed a clinical study of pneumococcal endocarditis (PE) in adults at 15 major Spanish hospitals during a 21-year period (1978-1998). During this time, 63 patients had PE due to Streptococcus pneumoniae diagnosed. Of the 63 isolates recovered from these patients, 24 (38%) and 6 (10%) showed resistance to penicillin (minimum inhibitory concentration [MIC], 0.1-4 microg/mL) and cefotaxime (MIC, 1 microg/mL), respectively. Twenty-two (35%) of the patients died. Left-side heart failure, but not penicillin resistance, was independently associated with a higher risk of death (odds ratio, 1.33; 95% confidence interval, 1.04-1.71; P=.026). Patients without meningitis who had PE due to penicillin-resistant S. pneumoniae could be treated with high-dose penicillin or a third-generation cephalosporin if the MIC for penicillin was < or =1 microg/mL. For patients with concurrent meningitis, high doses of cefotaxime could be used if the MIC for cefotaxime was < or =1 microg/mL. Early recognition of heart failure and surgery may help to decrease mortality.

Selective depletion of CD56(dim) NK cell subsets and maintenance of CD56(bright) NK cells in treatment-naive HIV-1-seropositive individuals.

Human immunodeficiency virus-I (HIV-1) infected patients show a gradual loss of natural killer (NK) cells that correlates with disease progression. However, the effect of HIV-1 infection on different NK cell subsets has not been fully characterized. In healthy individuals most NK cells are CD3-CD56+ and two different subpopulations, CD56(dim) and CD56(bright), can be distinguished by the mean fluorescence intensity. Although it was originally suggested that CD56(bright) NK cells represent the precursors of the CD56dim subpopulation, recent cumulative data indicate that CD56(bright) and CD56(dim) NK cells are phenotypically, functionally, and developmentally different NK cell subsets. In this study, the analysis of CD56(bright) and CD56(dim) NK subsets showed that neither the number nor the phenotype of CD56(bright) NK cells were significantly altered in treatment-naive HIV-1-infected individuals, whereas the number of CD56(dim) NK cells was decreased. We also have studied NK cell subsets defined by the expression of CD56 in combination with CD16, CD161, or CD94 molecules. Our results demonstrated a preferential decrease of CD3-CD56+ NK cells coexpressing CD16 and CD161 but lacking CD94 molecules. On the contrary an increased percentage of NK cells that do not express CD56 molecules but express CD16, CD161, or CD94 was also found in HIV-1-infected individuals. As it has been proposed that these CD56-negative NK cells expressing other NK cell receptors represent immature NK cells with low cytolytic capacity, our results support that a defective differentiation from immature CD56 negative NK cells to mature CD56(dim) NK cells occurs in HIV-1 infection.

NK-associated receptors on CD8 T cells from treatment-naive HIV-infected individuals: defective expression of CD56.

OBJECTIVES: This study addresses the detailed expression of natural killer (NK)- associated receptors on CD8 T lymphocytes in treatment-naive HIV-infected individuals. DESIGN: Experimental study analysing the expression of NK-associated receptors on peripheral blood T lymphocytes from HIV-infected individuals compared with healthy controls. METHODS: Flow cytometry was used to analyse the expression of CD56, CD16, CD94, NKG2A, NKB1, CD161, CD244, and perforin, according to the CD28 phenotype, on CD8(bright) T cells obtained from treatment-naive HIV-infected individuals and from healthy controls. RESULTS: The results showed that CD8(bright) T cells from treatment-naive HIV-infected individuals had a decreased expression of CD56 and that CD8(bright)CD56 cell numbers correlated with CD4 cell counts. NK-associated markers were preferentially expressed on CD8(bright)CD28 negative T cells, both in healthy controls and HIV-infected individuals. An increased expression of CD94, CD244, and perforin, which was the consequence of the expansion of the CD8(bright)CD28 negative T-cell subset, was also observed in HIV infection. CONCLUSIONS: As the CD8(bright)CD56 T cells are the mature cytolytic effector cells, the defective expression of CD56 on CD8(bright) T cells shown in HIV-infected individuals could be involved in the decreased peripheral blood T-cell cytotoxicity found in HIV infection.