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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.

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.

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Background Current information regarding bacteriemia in patients with solid tumors is scarce Methods To assess the etiology, clinical features and outcome in patients with solid tumors and bacteremia, we carried out a prospective multicenter study. Episodes of bacteriemia in adult cancer patients in 9 centers, from May 2014 to February 2021, were recorded. To identify factors associated with 30-day mortality, variables with p < 0.05 in univariate analysis were included in a logistic regression model for multivariate analysis Results Three hundred and thirty-two episodes of bacteremia were included, with 51% being women (mean age 59). The state of underlying disease was: recent diagnosis 27%, remission 27%, relapsed 29% and refractory 17%. Seventy-three percent had received chemotherapy in the last 30 days, 25% were receiving steroids. Neutropenia was present in 23% (mean duration 3 days). The most frequent sources were: abdominal 39%, urinary tract 21%, respiratory 15%, catheter 10% and skin and soft tissue 9%. The microorganisms were: Gram negative bacilli (GNB) 67% (Enterobacterales 84%), Gram positive cocci 36% (Staphylococcus aureus 33%) and polimicorbial 11%; 20% were multidrug resistant organisms (MDR-O), being 88% of them GNB (MDR-GNB). ESBL and KPC carbapenemase producing were the most frequent mechanisms of resistance. Mortality at day 7 and day 30 was 16% and 27%, respectively. In the univariate analysis, the risk factors for 30-day mortality were Charlson index, refractory underlying disease, use of steroids, polimicrobial bacteremia, Staphylococcus aureus, GNB resistant to carbapenems, APACHE and Pitt scores, hypotension, respiratory source and ICU admission. In multivariate analysis, risk factors for 30-day mortality were refractory underlying disease, GNB resistant to carbapenems and ICU admission, while 7-day clinical response was associated with lower mortality Conclusion Bacteremia is a serious complication in cancer patients, with high mortality. The state of underlying disease, infection caused by GNB resistant to carbapenems, and the severity of presentation are associated with increased mortality. Our results stress the importance of infection control measures and antibiotic stewardship to prevent colonization with MDR-O Disclosures All Authors: No reported disclosures