Rapid identification of pathogens directly from positive blood cultures (BC) in combination with an antimicrobial stewardship programme (ASP) is associated with improved antibiotic treatment and ...outcomes, but the effect of each individual intervention is less clear. The current study investigated the impact of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) versus conventional identification on antibiotic management in a setting with a well-established ASP and low resistance rates.
In this single-centre open label, controlled clinical trial 425 patients with positive BCs were allocated by weekday during a 1-year period to either MALDI-TOF directly from positive BCs or conventional processing. ASP was identical throughout the study period. The primary outcome was duration of intravenous antimicrobial therapy and was analysed in an intention-to-treat approach.
In all, 368 patients were analysed (MALDI-TOF n = 168; conventional n = 200) with similar baseline characteristics. Mean duration of intravenous antimicrobial therapy (12.9 versus 13.2 days, p 0.9) and length of stay (16.1 versus 17.9 days, p 0.3) were comparable. In the clinically significant bloodstream infection subgroup (n = 242) mean time from Gram-stain to active treatment was significantly shorter (3.7 versus 6.7 h, p 0.003). Admission to the intensive care unit after bloodstream infection onset was less frequent in the MALDI-TOF group (23.1 versus 37.2%, p 0.02).
Rapid identification of contaminated BCs (n = 126) resulted in a shorter duration of intravenous antimicrobial therapy (mean 4.8 versus 7.5 days, p 0.04). Rapid identification using MALDI-TOF directly from positive BCs did not impact on duration of intravenous antimicrobial therapy, but provided fast and reliable microbiological results and may improve treatment quality in the setting of an established ASP.
In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis ...in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.
Recurrence of prior invasive fungal infection (relapse rate of 30-50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival.
A ...prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100-150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection.
Forty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity).
Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population.
By understanding prognostic biomarkers, we gain insights into disease biology and may improve design, conduct, and data analysis of clinical trials and real-world data. In this context, we used the ...Flatiron Health Electronic Health Record-derived deidentified database that provides treatment outcome and biomarker data from >280 oncology centers in the USA, organized into 17 cohorts defined by cancer type.
In 122 694 patients, we analyzed demographic, clinical, routine hematology, and blood chemistry parameters within a Cox proportional hazard framework to derive a multivariable prognostic risk model for overall survival (OS), the ‘Real wOrld PROgnostic score (ROPRO)’. We validated ROPRO in two independent phase I and III clinical studies.
A total of 27 variables contributed independently and homogeneously across cancer indications to OS. In the largest cohort (advanced non-small-cell lung cancer), for example, patients with elevated ROPRO scores (upper 10%) had a 7.91-fold (95% confidence interval 7.45–8.39) increased death hazard compared with patients with low scores (lower 10%). Median survival was 23.9 months (23.3–24.5) in the lowest ROPRO quartile Q1, 14.8 months (14.4–15.2) in Q2, 9.4 months (9.1–9.7) in Q3, and 4.7 months (4.6–4.8) in Q4. The ROPRO model performance indicators C-index = 0.747 (standard error 0.001), 3-month area under the curve (AUC) = 0.822 (0.819–0.825) strongly outperformed those of the Royal Marsden Hospital Score C-index = 0.54 (standard error 0.0005), 3-month AUC = 0.579 (0.577–0.581). We confirmed the high prognostic relevance of ROPRO in clinical Phase 1 and III trials.
The ROPRO provides improved prognostic power for OS. In oncology clinical development, it has great potential for applications in patient stratification, patient enrichment strategies, data interpretation, and early decision-making in clinical studies.
•Clinical routine variables can be combined into a high-quality prognostic score Real wOrld PROgnostic score (ROPRO) for overall survival.•ROPRO can be used for patient matching and baseline risk adjustment in clinical studies.•ROPRO can support patient enrichment in early clinical trials.
Antibacterial resistance is emerging in patients undergoing haematopoietic stem cell transplantation (HSCT), and most data on the epidemiology of bloodstream infections (BSI)-causing pathogens come ...from retrospective single-centre studies. This study sought to investigate trends in the epidemiology of BSI in HSCT patients from a prospective multicentre cohort.
We investigated changes in the incidence of causative organisms of BSI during neutropenia among adult HSCT patients for 2002–2014. The data were collected from a prospective cohort for infection surveillance in 20 haematologic cancer centres in Germany, Austria and Switzerland (ONKO-KISS).
A total of 2388 of 15 181 HSCT patients with neutropenia (1471 allogeneic (61.6%) and 917 autologous (38.4%) HSCT) developed BSI (incidence 15.8% per year). The incidence of Gram-negative BSI increased over time both in patients after allogeneic HSCT (allo-HSCT) and autologous HSCT (auto-HSCT). BSI caused by Escherichia coli in allo-HSCT patients increased from 1.1% in 2002 to 3.8% in 2014 (3/279 vs. 31/810 patients, p <0.001), and the incidence of BSI caused by enterococci increased from 1.8% to 3.3% (5 vs. 27 patients, p <0.001). In contrast, the incidence of BSI due to coagulase-negative staphylococci decreased in allo-HSCT patients from 8.2% to 5.1%, (23 vs. 40 patients, p <0.001) and in auto-HSCT patients from 7.7% to 2.0% (13/167 vs. 30/540 patients; p = 0.028 for period 2002–2011). No significant trends were observed for the incidence of BSI due to methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or extended-spectrum β-lactamase-producing Enterobacteriaceae. The BSI case fatality remained unchanged over the study period (total of 477 fatalities, 3.1%).
The incidence of Gram-negative BSI significantly increased over time in this vulnerable patient population, providing evidence for reevaluating empiric therapy for neutropenic fever in HSCT patients.
Neutron and synchrotron X-ray diffraction spectra have been acquired during room temperature tensile deformation of a creep-resistant bainitic 1% CrMoV steel, in order to study the evolution of ...internal microstresses and load-sharing mechanisms between the ferrite matrix and the various carbides. Cementite takes load from the plastifying matrix at the onset of macroscopic plasticity resulting in residual interphase stresses. Single peak fitting indicates an elastic anisotropic behaviour of cementite.
We assessed changes in sexual behavior among people with human immunodeficiency virus (HIV) over 20 years. Condom use with stable partners steadily declined from over 90 to 29 since the Swiss U U ...statement, with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during coronavirus disease 2019 (COVID-19) social distancing.
We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant ...recipients. Risk factors associated with CMV disease and graft failure‐free survival were analyzed using Cox regression models. One thousand two hundred thirty‐nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R− vs. R+, hazard ratio HR 5.36 95% CI 3.14–9.14, p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 95% CI 0.63–2.17, p = 0.63). CMV disease was not associated with a lower graft failure‐free survival (HR 1.27 95% CI 0.64–2.53, p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure‐free survival after a median of 1.05 years of follow‐up (HR 1.63 95% CI 1.01–2.64, p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.
In this nationwide cohort of solid organ transplant recipients, the authors find that the incidence of cytomegalovirus disease is similar irrespective of the antiviral preventive strategy used (preemptive vs. prophylaxis), although patients who received antiviral prophylaxis have better graft failure‐free survival.
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