Letermovir Prophylaxis for CMV Reactivation in Allogeneic Stem Cell Recipients: A Retrospective Single Center Analysis.

BACKGROUND/AIM: Cytomegalovirus (CMV) reactivation is one of the most clinically significant complications in allogeneic stem cell recipients and a frequent cause for transplantation related mortality. Letermovir is a newly available and recently approved drug for CMV prophylaxis. In a retrospective single center analysis, we investigated the benefit of letermovir as CMV prophylaxis in allogeneic stem cell recipients. PATIENTS AND METHODS: We included 48 CMV-seropositive transplant recipients from January 2017 to August 2020 from our department. We compared the rate of CMV reactivation in patients who received letermovir as prophylaxis from day 0 after allogeneic stem cell transplantation (alloSCT) with a control group that did not receive CMV prophylaxis. The primary endpoint was CMV reactivation and was defined as an increase of CMV copies over 1250 Ul/ml in the peripheral blood; secondary endpoints were overall survival (OS) up to 180 days, engraftment and all-cause mortality. RESULTS: We included 21 patients in the control group and 27 patients in the letermovir group. Letermovir treatment led to a significantly reduced incidence of CMV reactivation after alloSCT (33.3% in the letermovir group versus 76.2% in the control group, p<0.001). The OS at day 180 was 80.9% in the control group versus 92.6% in the letermovir group (p<0.05). The median duration of letermovir prophylaxis was 192±104 days. CONCLUSION: Our results indicate that letermovir prophylaxis is associated with a significant lower risk of CMV reactivation and improved overall survival in CMV-seropositive stem cell recipients. Moreover, a prolonged use of letermovir prophylaxis might be a survival benefit.

Conditioning with fludarabine and treosulfan compared to FLAMSA-RIC in allogeneic stem cell transplantation for myeloid malignancies: a retrospective single-center analysis.

Reduced intensity conditioning (RIC) and reduced toxicity conditioning (RTC) regimens enable allogeneic hematopoietic stem cell transplantation (alloSCT) to more patients due to reduction in transplant-related mortality (TRM). The conditioning regimens with fludarabine and treosulfan (Flu/Treo) or fludarabine, amsacrine, cytarabine (FLAMSA)-RIC have shown their efficacy and tolerability in various malignancies. So far, no prospective study comparing the two regimens is available. Two studies compared the regimens retrospectively, in which both provided similar outcome. In this retrospective, single-center analysis, these two regimens were compared with regard to outcome, rate of acute and chronic graft versus host disease (GvHD), and engraftment. 113 consecutive patients with myeloid malignancies who received Flu/Treo or FLAMSA-RIC conditioning prior to alloSCT between 2007 and 2019 were included. Except for age, previous therapies, and remission status before alloSCT, patient characteristics were well balanced. The median follow-up time within this analysis was 44 months. There was no significant difference in absolute neutrophil count (ANC) or platelet engraftment between the two conditioning regimens. Overall survival (OS), the relapse-free survival (RFS), and the TRM were not significantly different between the two cohorts. The rate of GvHD did not differ between the two groups. In summary, this retrospective analysis shows that there is no major difference regarding tolerability and survival between the Flu/Treo and FLAMSA-RIC regimens. Despite several limitations due to uneven distribution concerning age and remission status, we demonstrate that Flu/Treo and FLAMSA-RIC provide similar outcomes and are feasible in older and intensively pre-treated patients.

Clinical and microbiological features and outcomes of mucormycosis in critically ill patients.

INTRODUCTION: Mucormycosis is a rare invasive fungal infection with high mortality in patients with severe underlying predisposing factors causing immunosuppression. The exact incidence of mucormycosis and the optimal therapeutic approach is difficult to determine, especially in severe cases, due to the rarity of the disease. The new second-generation triazole isavuconazole provides an alternative treatment option which may represent a potential benefit in severe cases. MATERIALS AND METHODS: A retrospective case series was conducted of patients with a positive laboratory culture for Mucorales and consistent clinical findings who required intensive care treatment. Patient characteristics including demographics, comorbidities, microbiological analysis, specific antifungal therapy and clinical outcome were analysed. RESULTS: Fifteen critically ill patients with Mucorales detected between 2016 and 2019 were included in this study; the crude mortality rate was 100%. At the time of diagnosis of mucormycosis, 80% of subjects had relevant medical immunosuppression and 53.3% of subjects had neutropenia. Manifestation of mucormycosis was pulmonary in 53.3% of subjects, rhino-orbital in 20% of subjects and disseminated in 26.7% of subjects. Notably, 40% of all patients had received antifungal prophylaxis prior to mucormycosis, mainly with posaconazole due to underlying haematological malignancy, thus possibly representing break-through infections. Antifungal therapy for invasive mucormycosis was administered in 80% of subjects for a median duration of 16 days. CONCLUSION: In this retrospective cohort analysis of intensive care patients, the prognosis of mucormycosis was extremely poor. An aggressive strategy for diagnosis and treatment is essential for intensive care patients with mucormycosis. There is a need for further research to determine if combination therapy in higher dosages or prompt surgery is beneficial in severe critically ill patients.

A diagnostic algorithm for detection of urinary tract infections in hospitalized patients with bacteriuria: The "Triple F" approach supported by Procalcitonin and paired blood and urine cultures.

For acute medicine physicians, distinguishing between asymptomatic bacteriuria (ABU) and clinically relevant urinary tract infections (UTI) is challenging, resulting in overtreatment of ABU and under-recognition of urinary-source bacteraemia without genitourinary symptoms (USB). We conducted a retrospective analysis of ED encounters in a university hospital between October 2013 and September 2018 who met the following inclusion criteria: Suspected UTI with simultaneous collection of paired urinary cultures and blood cultures (PUB) and determination of Procalcitonin (PCT). We sought to develop a simple algorithm based on clinical signs and PCT for the management of suspected UTI. Individual patient presentations were retrospectively evaluated by a clinical "triple F" algorithm (F1 ="fever", F2 ="failure", F3 ="focus") supported by PCT and PUB. We identified 183 ED patients meeting the inclusion criteria. We introduced the term UTI with systemic involvement (SUTI) with three degrees of diagnostic certainty: bacteremic UTI (24.0%; 44/183), probable SUTI (14.2%; 26/183) and possible SUTI (27.9%; 51/183). In bacteremic UTI, half of patients (54.5%; 24/44) presented without genitourinary symptoms. Discordant bacteraemia was diagnosed in 16 patients (24.6% of all bacteremic patients). An alternative focus was identified in 67 patients, five patients presented with S. aureus bacteremia. 62 patients were diagnosed with possible UTI (n = 20) or ABU (n = 42). Using the proposed "triple F" algorithm, dichotomised PCT of < 0.25 pg/ml had a negative predictive value of 88.7% and 96.2% for bacteraemia und accordant bacteraemia respectively. The application of the algorithm to our cohort could have resulted in 33.3% reduction of BCs. Using the diagnostic categories "possible" or "probable" SUTI as a trigger for initiation of antimicrobial treatment would have reduced or streamlined antimicrobial use in 30.6% and 58.5% of cases, respectively. In conclusion, the "3F" algorithm supported by PCT and PUB is a promising diagnostic and antimicrobial stewardship tool.