Characteristics of Pseudomonas aeruginosa infection in intensive care unit before (2007-2010) and after (2011-2014) the beginning of an antimicrobial stewardship program.

Objectives: To investigate the factors associated with Pseudomonas aeruginosa isolates in intensive care unit (ICU) before and after an antimicrobial stewardship program. Materials: Monocentric retrospective cohort study. Patients admitted to the ICU in 2007-2014 were included. Characteristics of P. aeruginosa patients were compared to overall ICU population. Clinical and microbiological characteristics of P. aeruginosa patients before (2007-2010) and after (2011-2014) the beginning of the AMP were compared. Results: Overall, 5,263 patients were admitted to the ICU, 274/5,263 (5%) had a P. aeruginosa isolate during their staying. In 2011-2014, the percentage P. aeruginosa isolates reduced (7% vs 4%, P ≤ .0001). Patients with P. aeruginosa had higher rates of in-hospital death (43% vs 20%, P < .0001) than overall ICU population. In 2011-2014, rates of multidrug-resistant (11% vs 2%, P = .0020), fluoroquinolone-resistant (35% vs 12%, P < .0001), and ceftazidime-resistant (23% vs 8%, P = .0009) P. aeruginosa reduced. Treatments by fluoroquinolones (36% vs 4%, P ≤ .0001), carbapenems (27% vs 9%, P = .0002), and third-generation cephalosporins (49% vs 12%, P ≤ .0001) before P. aeruginosa isolation reduced while piperacillin (0% vs 13%, P < .0001) and trimethoprim-sulfamethoxazole (8% vs 26%, P = .0023) increased. Endotracheal intubation reduced in 2011-2014 (61% vs 35%, P < .0001). Fluoroquinolone-resistance was higher in patients who received endotracheal intubation (29% vs 17%, P = .0197). Previous treatment by fluoroquinolones (OR = 2.94, P = .0020) and study period (2007-2010) (OR = 2.07, P = .0462) were the factors associated with fluoroquinolone-resistance at the multivariate analysis. Conclusions: Antibiotic susceptibility in P. aeruginosa isolates was restored after the reduction of endotracheal intubation, fluoroquinolones, carbapenems, and third-generation cephalosporins and the increased use of molecules with a low ecological footprint, as piperacillin and trimethoprim-sulfamethoxazole.

The Predictive Value of Cell Blood Count Parameters to Diagnose Pulmonary Embolism in Patients with SARS-CoV-2 Infection: A Case Control Study.

Introduction: Acute pulmonary embolism (aPE) is frequently associated with coronavirus infectious disease-2019 (COVID-19) with an incidence of more than 16%. Among the new promising biomarkers of aPE, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) showed correlations with aPE prognosis. The aim of this study was to conduct an exploratory analysis to check the possible role of cell blood count (CBC) parameters as diagnostic and prognostic biomarkers of aPE in COVID-19 patients. Materials and Methods: A case control study was conducted. Two populations were compared: (i) patients hospitalised from 31 January 2020 to 30 June 2021 with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection and aPE confirmed at angio computed tomography (aCT) or pulmonary scintigraphy (COVID-19 aPE group); (ii) patients hospitalised from 31 January 2017 to 30 June 2021 without SARS-CoV-2 infection whose suspicion of aPE was excluded by aCT or pulmonary scintigraphy (no-aPE group). Results: Overall, 184 patients were included in the study, 83 in COVID-19 aPE group and 101 in no-aPE group. At the univariate analysis, COVID-19 patients with aPE had higher NLR, PLR, neutrophil and lymphocyte counts than patients without aPE (p < 0.05). No significant difference was found in mean platelet volume and platelet counts. No difference in mortality rate was detected. At the multivariate analysis, neutrophil and lymphocyte counts were both associated with diagnostic of aPE while no CBC parameters were associated with mortality at day#7. Conclusions: Neutrophiland lymphocyte counts could be predictors of the early detection of aPE in COVID-19 patients. The value of CBC indices as biomarkers of aPE in daily clinical practice needs to be investigated in further studies.

Extreme gonococcal susceptibility associated with acquired complement deficiency secondary to hypocomplementemic urticarial vasculitis and systemic lupus erythematosus.

Gonococcal infection is rarely associated with septic shock. We describe a recurrent case of septic shock related to disseminated gonococcemia in a patient with systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, and discuss the implication of profound acquired complement deficiency secondary to these auto-immune diseases. This case raises the question of systematic antibioprophylaxis in patients with acquired complement deficiency.

Coexistence of Acquired Hemophilia and Antiphospholipid Serology in Monoclonal Gammopathy Patient.

Acquired hemophilia is a rare coagulopathy with hemorrhage into the skin, muscle, or soft tissues and mucous membranes and caused by inhibitor antibodies, mainly against FVIII. We report a case of acquired hemophilia presenting with diffuse cutaneous hemorrhage and hemothorax. The patient was found to have acquired an FVIII inhibitor and a high titer of anti ß2 glycoprotein 1 IgG and IgM, and anticardiolipin IgM in the context of IgA kappa-type monoclonal gammopathy. He received 3 injections of recombinant factor VII (rFVIIa) and blood transfusion. He was started on steroids and oral cyclophosphamide for 6 weeks. Thromboprophylaxis with aspirin at 100 mg/day was started 3 months after discharge. Antiphospholipid antibodies remained positive after 3 months as well as prolonged aPTT, factor VIII raised at 100%, and the inhibitor was not detected. The association between acquired hemophilia and antiphospholipid antibodies is rare and its distinction is mandatory because clinical presentation ranges from massive hemorrhage to thrombosis.

Successful benralizumab for eosinophilic myocarditis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterised by many features, including asthma, allergic rhinitis, peripheral and tissue eosinophilia, and vasculitis. Its pathophysiology is still unclear and we suggest that there are different phenotypes of EGPA, which may respond differently to available treatments. Within the most promising targeting biotherapy, benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has proved both highly effective and safe. We report herewith a case of EGPA presenting a myocarditis relapse successfully treated with benralizumab.

Design of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects.

Human leishmaniasis is a public health problem worldwide for which the development of a vaccine remains a challenge. T cell-mediated immune responses are crucial for protection. Peptide vaccines based on the identification of immunodominant T cell epitopes able to induce T cell specific immune responses constitute a promising strategy. Here, we report the identification of human leukocyte antigen class-I (HLA-I) and -II (HLA-II)-restricted multi-epitope peptides from Leishmania proteins that we have previously described as vaccine candidates. Promastigote Surface Antigen (PSA), LmlRAB (L. major large RAB GTPase) and Histone (H2B) were screened, in silico, for T cell epitopes. 6 HLA-I and 5 HLA-II-restricted multi-epitope peptides, able to bind to the most frequent HLA molecules, were designed and used as pools to stimulate PBMCs from individuals with healed cutaneous leishmaniasis. IFN-γ, IL-10, TNF-α and granzyme B (GrB) production was evaluated by ELISA/CBA. The frequency of IFN-γ-producing T cells was quantified by ELISpot. T cells secreting cytokines and memory T cells were analyzed by flow cytometry. 16 of 25 peptide pools containing HLA-I, HLA-II or HLA-I and -II peptides were able to induce specific and significant IFN-γ levels. No IL-10 was detected. 6 peptide pools were selected among those inducing the highest IFN-γ levels for further characterization. 3/6 pools were able to induce a significant increase of the percentages of CD4+IFN-γ+, CD8+IFN-γ+ and CD4+GrB+ T cells. The same pools also induced a significant increase of the percentages of bifunctional IFN-γ+/TNF-α+CD4+ and/or central memory T cells. We identified highly promiscuous HLA-I and -II restricted epitope combinations from H2B, PSA and LmlRAB proteins that stimulate both CD4+ and CD8+ T cell responses in recovered individuals. These multi-epitope peptides could be used as potential components of a polytope vaccine for human leishmaniasis.

Trypanosomatid Infections: How Do Parasites and Their Excreted-Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

Mononuclear phagocytes (monocytes, dendritic cells, and macrophages) are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO) synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted-secreted (ES) molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage's inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the development of vaccines or immunotherapeutic approaches.