Following a primary immune response, T cell memory occurs when a subset of antigen specific T cells resist peripheral selection by acquiring resistance to TCR induced death. Recent data have implicated Bim as an essential mediator of the contraction phase of T cell immunity. Herein, we describe that SDF-1α ligation of CXCR4 on activated T cells, promotes two parallel processes which favor survival, phospho-inactivation of Foxo3A as well as BimEL degradation, both in an Akt and Erk dependent manner. Activated primary CD4 T cells treated with SDF-1α therefore become resistant to the pro-apoptotic effects of TCR ligation or IL-2 deprivation and accumulate cells of a memory phenotype. Unlike SDF-1α, gp120 ligation of CXCR4 has the opposite effect as it causes p38 dependent BimEL upregulation. However when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α driven effects of BimEL degradation and acquired resistance to TCR induced death predominate. These results provide a novel causal link between SDF-1α induced chemotaxis, degradation of BimEL and the development of CD4 T cell memory.

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Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

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Data about short courses of antibiotic therapy for Gram-negative bacilli (GNB) bacteremia in immunosuppressed patients are limited. This is a prospective observational study performed on adult patients with cancer and hematopoietic stem cell transplant (HSCT) who developed GNB bacteremia and received appropriate empirical antibiotic therapy (EAT), had a clinical response within 7 days and survived 48 h after the end of therapy. They received antibiotic therapy in the range of 7–15 days and were divided into short course, with a median of 7 days (SC), or long course, with a median of 14 days (LC). Seventy-four patients were included (SC: 36 and LC: 38). No differences were observed in baseline characteristics or in the presence of neutropenia: 58.3% vs. 60.5% (p = 0.84). Clinical presentation and microbiological characteristics were similar in SC and LC, respectively: clinical source of bacteremia 72.2% vs. 76.3% (p = 0.68); shock 2.8% vs. 10.5% (p = 0.35) and multidrug-resistant GNB 27.8% vs. 21.1% (p = 0.50). Overall, mortality was 2.8% vs. 7.9% (p = 0.61), and bacteremia relapse was 2.8% vs. 0 (p = 0.30). The length of hospitalization since bacteremia was 7 days (interquartile range (IQR), 6–15) for SC and 12 days (IQR, 7–19) (p = 0.021) for LC. In the case of patients with cancer or HSCT and GNB bacteremia who receive appropriate EAT with clinical response, 7 days of antibiotic therapy might be adequate.