Febrile neutropenia (FN) is the main reason for antibiotic prescription in hematology wards where, on the other hand, antibiotic stewardship (AS) is poorly explored. The objectives of the present study were to evaluate (1) the impact of an AS intervention on antibiotic consumption and (2) the applicability and acceptance rate of the intervention and its clinical impact. A persuasive AS intervention based on European Conference on Infection in Leukaemia (ECIL) guidelines for FN was implemented in a high-risk hematology ward in a tertiary referral public university hospital. This included the creation and diffusion of flow charts on de-escalation and discontinuation of antibiotics for FN, and the introduction in the team of a doctor dedicated to the implementation of flow charts and to antibiotic prescription revision. All consecutive patients receiving antibiotics during hospitalization were included. A segmented linear regression model was performed for the evaluation of antibiotic consumption, taking into account 1-year pre-intervention period and 6-month intervention period. Overall, 137 consecutive antibiotic prescriptions were re-evaluated, 100 prescriptions were for FN. A significant reduction of the level of carbapenem consumption was observed during the intervention period (level change (estimate coefficient ± standard error) = - 135.28 ± 59.49; p = 0.04). Applicability and acceptability of flow charts were high. No differences in terms of intensive care unit transfers, bacteremia incidence, and mortality were found. A persuasive AS intervention in hematology significantly reduced carbapenem consumption without affecting outcome and was well accepted. This should encourage further applications of ECIL guidelines for FN.

Invasive fungal infections (IFI) are complications after liver transplantation involving high morbidity and mortality. (1,3)-β-d-glucan (BG) is a biomarker for IFI, but its utility remains uncertain. This study was designed to evaluate the impact of BG following their diagnosis. Between January 2013 and May 2016, 271 liver transplants were performed in our institution. Serum samples were tested for BG (Fungitell®, Associates Cape Code Inc., Falmouth, MA, USA) at least weekly between liver transplantation and the discharge of patients. Nineteen patients (7%) were diagnosed with IFI, including 13 cases of invasive candidiasis (IC), eight cases of invasive pulmonary aspergillosis, and one case of septic arthritis due to Scedosporium apiospernum. Using a single BG sample for the primary analysis of IFI, 95% (21/22) of the subjects had positive BG (>80 pg/mL) at the time of IFI diagnosis. The area under the ROC curves to predict IFI was 0.78 (95% CI: 0.73–0.83). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BG for IFI were 75% (95% CI: 65–83), 65% (62–68), 17% (13–21), and 96% (94–97), respectively. Based on their high NPV, the BG test appears to constitute a good biomarker to rule out a diagnosis of IFI.

CASE REPORTS Anti-C5 antibody treatment for delayed hemolytic transfusion reactions in sickle cell disease Delayed hemolytic transfusion reaction (DHTR) is an unpredictable severe complication of transfusion in patients with sickle cell disease (SCD). It presents clinically as a vaso-occlusive crisis (VOC), often associated with the failure of one or more organs, after the transfusion of packed red blood cells (pRBC). 1,2 Hyperhemolysis is encountered in the most severe forms. Both transfused and autologous red blood cells (RBC) are lysed. The mechanisms underlying DHTR remain unclear. Continuous variables are expressed as means ± one standard deviation (SD) or medians (MD, [interquartile range]), depending on whether they are normally or asymmetrically distributed. Categorical variables are expressed as numbers (%). For comparison with the largest published delayed hemolytic transfusion reaction (DHTR) series, the data in column 2 are reprinted from Habibi et al.1 with permission. The patients of our series, who received anti-C5 antibody, had very severe DHTR with hyperhemolysis (P-values in column 3 compare our patients with those of the historical series). *Six patients had not even been discharged, due to the severity of their DHTR, **All patients in both series also received supportive vaso-occlusive crisis (VOC) treatment, hydration, oxygenation, and analgesia. † Values were converted to g/L (from g/dL in Habibi et al.). ‡ Delta hemoglobin (Hb) is the difference between the highest and lowest values available post-transfusion. F: female; M: male; pRBC: packed red blood cells, LDH: lactate dehydrogenase, EPO: erythropoietin.

Background: Delayed hemolytic transfusion reaction (DHTR) is an unpredictable and severe complication of transfusion, especially in Sickle Cell Disease (SCD) patients (Habibi Am J Hematol 2016). The clinical presentation is a vaso occlusive crisis (VOC), often associated with one or more organ failures, after packed red blood cell transfusion (pRBC). The hypothesis of complement activation through the classical pathway by alloantibodies and/or the alternative pathway by free heme (released by hemolysis) suggests that an inhibitor of complement activation may be a treatment option for DHTR. Methods: This retrospective study focuses on the SCD patients who received anti-C5 monoclonal antibody during DHTR treatment after consulting with our French SCD referral center between 2013 and 2018. DHTR diagnosis associated VOC signs occurring 5 to 20 days after pRBC transfusion, with no other cause for intravascular hemolysis, and one or more of the following: - rapid decrease in, or unexpectedly low, hemoglobin A (HbA) concentration - hemoglobinuria defined by dark urines - direct antiglobulin test (DAT) positivity or new antibody formation. The treatment efficacy was evaluated through patients' clinical and biological data. Findings: Sixteen patients received anti-C5 for a DHTR defined by a VOC 5 to 20 days after a transfusion and the following criteria: 12 had low HbA or rapid decrease of HbA, 10 had hemoglobinuria, and 10 had positive DAT or antibody formation. One patient received anti-C5 for hyperhemolysis without being able to discriminate DHTR from hemolysis under Extracorporeal Membrane Oxygenation and was excluded from the analysis. The 16 patients included in the analysis had severe DHTR at diagnosis, with one or more organ failures (N=7), median hemoglobin concentration 57 g/L [30-97], LDH 2807 UI/L [510-12500], total bilirubin 92 mmol/L [15-730]. Two additional patients had organ failures during the follow-up. Lowest hemoglobin concentration was 32 g/L [19-58] and highest LDH 4238 UI/L [510-24000]. One to 3 anti-C5 doses were given at 1 week intervals, associated with symptomatic treatment (hydration, oxygen, analgesia; N=16), erythropoietin (N=15), pRBC transfusions (N=12), immunoglobulins (N=8), plasma exchange (N=4), steroids (N=1). The outcome was favorable for 13 patients. The number of pRBC transfused were limited as much as possible. Three patients died. All three had acute liver failure that required emergency liver transplant. Two patients improved after anti-C5 and could be grafted, but died of infectious complications unrelated to anti-C5: Klebsiella pneumoniae pulmonary infection 11 days after transplant for one, and digestive and urinary infection 47 days after transplant for the other. For the third patient, no compatible organ could be found. Conclusion: In association with other therapies (EPO, plasma exchange, limiting pRBC transfusions), anti-C5 can be a treatment option for severe DHTR despite its high cost, in the absence of effective alternatives. Disclosures Michel: Amgen: Consultancy; Rigel: Consultancy; Novartis: Consultancy. Bartolucci:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Anti-C5 is currently used to treat paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

We describe a sudden 2-week outbreak due to a blaNDM-1Citrobacter amalonaticus strain in a 22-bed digestive rehabilitation center. Three of the 5 colonized patients received long-term rifaximin treatment to prevent hepatic encephalopathy. The strains were genotypically identical, phenotypically resistant to rifampin, and harbored arr-3, a rifampin adenosine diphosphate-ribosyl transferase.