Pseudomonas aeruginosa bacteremia over a 10-year period: multidrug resistance and outcomes in transplant recipients

Abstract: Aim. Transplant recipients are at risk for hospital‐acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most life‐threatening. Methods. Over a 10‐year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non‐transplant patients. Results. Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non‐transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non‐transplant patients (n=391) (odds ratio [OR] 3.47; 95% confidence interval [CI] 2.34–5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51–3.76, P<0.001), hospital‐acquired BSI (OR 2.41; 95% CI 1.39–4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15–3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non‐transplant patients (OR 1.55; 95% CI 0.87–2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71–37.42, P=0.008). Conclusions. Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.     

Kinetics of interferon‐gamma producing cytomegalovirus (CMV)‐specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation

Background. Deficiencies in cytomegalovirus (CMV)‐specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). Methods. A time‐dependent analysis was conducted to determine the association between the percentages and kinetics of interferon‐gamma‐producing CMV‐specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients. Results. Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18–3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99–1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early‐1 (HR: 1.2; 95% CI: 1.01–1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0–1.27; P=0.060) were associated with time‐to‐CMV viremia. Furthermore, a higher degree in the decline of CMV lysate‐activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96–1.36; P=0.125) and CMVpp65‐activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03–1.78; P=0.031) was suggestive of or significantly associated with time‐to‐CMV viremia. Conclusions. Higher levels of CMV‐specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV‐specific T lymphocytes suggests that severe disruption in homeostatic CMV‐specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.     

Outcome and risk factors for late-onset complications 24 months beyond allogeneic hematopoietic stem cell transplantation

Objectives: The aim of this retrospective study was to assess the incidence of late complications occurring ≥2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T‐cell depletion strategy. Methods: Between 1984 and 2004, 142 patients were eligible for the study. Total body irradiation (TBI) was carried out in 85% of the patients and T‐cell depletion in 84%. Results: Non‐relapse mortality (NRM) was 3% (95% CI 0–11) at 10 years, and serious late events affected a substantial number of patients. The cumulative incidence (CI) of chronic graft‐versus‐host disease (cGvHD) was 30% (95% CI 23–40), and that of infectious complications was 17% (95% CI 11–23). Multivariate analysis showed a higher risk for late complications in patients with cGvHD (HR 1.9, 95% CI 1.2–3.2, P = 0.011) and patients receiving methylprednisolone during conditioning (HR 1.9, 95% CI 1.1–3.3, P = 0.019 1), patients with cGvHD also having a higher risk for NRM (HR 13.2, 95% CI 1.2–143, P = 0.03), as well as those receiving steroids for >3 months (HR 40.3, 95% CI 2.3–718, P = 0.02) and those receiving antithymocyte globulin (HR 9.6, 95% CI 0.8–68, P = 0.024). Conclusions: A significant proportion of long‐term survivors of HSCT had late complications. cGvHD remained an important risk factor for late complications despite T‐cell depletion resulting in immunosuppression and infectious complications.     

BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts

The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twenty-seven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both P<0.001), and with an HLA-mismatched donor (P<0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0-21.7; P=0.001), MC (OR 6.0; 95% CI 2.1-17.3; P<0.001) and URD (OR 3.4; 95% CI 1.1-10.6; P=0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8-19.3; P=0.004) and MC (OR 5.9; 95% CI 1.3-11.3; P=0.009) increased the risk for HC only with a URD, but not with an RD graft.     

Bacteremia During Early Post-allogeneic Hematopoietic Stem Cell Transplantation Period: A Single Center Experience

Bacteremia is a significant complication of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to study bacteremia occurring during early post-transplant period at Bone Marrow Transplantation Unit of Ain Shams University regarding its risk factors and impact on survival. Patients performing allogeneic HSCT were followed up for occurrence of bacteremia. Survival status was assessed at 180 days post-transplant. Bacteremia occurred in 53.3 % of patients. On univariate analysis, CD34 +ve cell dose (P = 0.004), duration of neutropenia (P = 0.018), time interval between day of stem cell infusion and day of neutrophil engraftment (P = 0.043) and > 1 apheresis days (P = 0.040) were associated with higher rates of bacteremia. On multivariate analysis, CD34 +ve cell dose (P = 0.002) and apheresis day number (P = 0.038) remained significant. There was significant difference between patients who developed bacteremia and those who did not regarding overall survival (OS) (P = 0.042). Patients developing bacteremia caused by Gram negative bacteria (GNB) had lower OS than Gram positive bacteria (GPB) (P < 0.001). In conclusion, stem cell dose and apheresis day number influence bacteremia risk. Also, Gram negative bacteremia has negative impact on allogeneic transplant recipient survival rates.     

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients

We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.     

Increased regulatory T cell graft content is associated with improved outcome in haematopoietic stem cell transplantation: a systematic review

Allogeneic haematopoietic stem cell transplant (HSCT) recipients are at increased risk of morbidity and mortality, often due to the development of acute or chronic graft‐versus‐host disease (GVHD). Low numbers or proportions of regulatory T cells (Tregs) have been reported in patients who develop GVHD. We undertook a systematic review of studies that reported the Treg composition of HSCT grafts in patients with haematological malignancies. Fourteen eligible studies were identified, eight of which stratified patients by Tregs (absolute dose or ratio to CD3+ or CD4+ cells). Meta‐analyses showed that high levels of Tregs in the grafts were associated with improved overall survival [hazard ratio (HR) 0·42, 95% confidence interval (CI) 0·23–0·74, P  = 0·003, 2 studies], with a significant reduction in non‐relapse mortality (HR 0·30, 95% CI 0·14–0·64, P  = 0·002, 2 studies) and a reduced risk of acute GVHD (relative risk (RR) 0·59, 95% CI 0·40–0·89, P  = 0·01, 6 studies). The consistency of these findings strongly suggests that the Treg composition of HSCT grafts has a powerful effect on the success of allogeneic HSCT. The major challenge is to translate these findings into better selection of allografts and future donors to provide a substantial improvement in allogeneic HSCT outcomes and practice.     

Psychoactive medications and crash involvement requiring hospitalization for older drivers: a population-based study

OBJECTIVES: To determine the association between psychoactive medications and crash risk in drivers aged 60 and older. DESIGN: Retrospective population‐based case‐crossover study. SETTING: A database study that linked the Western Australian Hospital Morbidity Data System and the Pharmaceutical Benefits Scheme. PARTICIPANTS: Six hundred sixteen individuals aged 60 and older who were hospitalized as the result of a motor vehicle crash between 2002 and 2008 in Western Australia. MEASUREMENTS: Hospitalization after a motor vehicle crash. RESULTS: Greater risk for a hospitalization crash was found for older drivers prescribed benzodiazepines (odds ratio (OR)=5.3, 95% confidence interval (CI)=3.6–7.8, P<.001), antidepressants (OR=1.8, 95% CI=1.0–3.3, P=.04), and opioid analgesics (OR=1.5, 95% CI=1.0–2.3, P=.05). Crash risk was significantly greater in men prescribed a benzodiazepine (OR=6.2, 95% CI=3.2–12.2, P<.001) or an antidepressant (OR=2.7, 95% CI=1.1–6.9, P=.03). Women prescribed benzodiazepines (OR=4.9, 95% CI=3.1–7.8, P<.001) or opioid analgesics (OR=1.8, 95% CI=1.1–3.0, P=.03) also had a significantly greater crash risk. Subgroup analyses further suggested that drivers with (OR=4.0, 95% CI=2.9–8.1, P<.001) and without (OR=6.0, 95% CI=3.8–9.5, P<.001) a chronic condition who were prescribed benzodiazepines were at greater crash risk. Drivers with a chronic condition taking antidepressants (OR=3.4, 95% CI=1.3–8.5, P=.01) also had a greater crash risk. CONCLUSION: Psychoactive medication usage was associated with greater risk of a motor vehicle crash requiring hospitalization in older drivers.     

Enterococcal bacteremia is associated with increased risk of mortality in recipients of allogeneic hematopoietic stem cell transplantation

Background.?Enterococci are an important cause of healthcare-associated infections. We retrospectively analyzed risk factors and outcome of vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE) infections. Methods.?Seven hundred fifty-two patients who received hematopoietic stem cell transplants from 2004 through 2008 at the University of Minnesota were included. Results.?Ninety-three patients had enterococcal bloodstream infection (BSI) during the first year after transplant. Vancomycin resistance was observed in 66% and 31% of isolates in adults and children, respectively. Cumulative incidence of VRE and VSE bacteremia was 6.6% (95% confidence interval [CI], 4.8%-8.4%) and 5.7% (95% CI, 4.0%-7.4%), respectively. Colonization with VRE before or after transplant was a risk factor for VRE bacteremia (odds ratio [OR], 3.3 [95% CI, 1.3-8.3] and 7.0 [95% CI, 4.0-14.8], respectively). Delay in engraftment increased the incidence of VRE bacteremia from 4.5% (95% CI, 2.9-6.6) if engrafted before day 21 and to 15% (95% CI, 3.2%-38%) if engrafted between days 36 and 42. In adults, mortality 30 days after infection was 38% for both VRE (95% CI, 25%-54%) and VSE cases (95% CI, 21%-62%). The hazard ratio for all-cause mortality up to 1 year after transplant was 4.2 (95% CI, 3.1-6.9) and 2.7 (95% CI, 1.4-5.1) for patients with VRE and VSE BSIs, respectively, compared to patients without enterococcal BSI. In pediatric patients, mortality 30 days after VRE and VSE bacteremia was 20% (95% CI, 5.4%-59%) and 4.5% (95% CI, .6%-28%), respectively. Conclusion.?High rates of vancomycin resistance and association of enterococcal infections with significant mortality warrant further efforts to optimize prevention and management of these infections.     

Risk factors and clinical outcomes of pediatric liver transplant recipients with post‐transplant lymphoproliferative disease in a multi‐ethnic Asian cohort

Background

We aimed to evaluate clinical characteristics, risk factors, and disease outcomes for liver transplant recipients (LTR) with post‐transplant lymphoproliferative disease (PTLD) at our center.

Methods

Retrospective review of data of all pediatric LTR (1991‐2015) was conducted.

Results

The overall incidence of PTLD was 16.4% (18/110), the majority (13/18) were early lesions, while 3/18 were polymorphic/monomorphic PTLD. The risk factors significant on univariate analysis were as follows: mean age (years) at transplant (1.66 vs 4.76, P = .006); age <2 years at transplant (odds ratio [OR] 3.53 [95% confidence interval [CI]: 1.16‐10.73], P = .026); cytomegalovirus (CMV) primary infection (OR 11.39 [95% CI: 3.44‐37.7], P < .001); recipient CMV seronegativity (OR 7.50 [95% CI: 2.02‐27.78], P = .003); presence of CMV end‐organ disease (OR 4.00 [95% CI: 1.22‐13.16], P = .022); Chinese ethnicity; and higher mean duration of intravenous ganciclovir prophylaxis. In multivariate analysis, CMV primary infection (OR 5.22 [95% CI: 1.25‐21.87], P = .024), CMV seronegativity (OR 5.91 [95% CI: 1.13‐30.90, P = .035]), and having acute cellular rejections (ACR) prior to PTLD (OR 5.53 [95% CI: 1.43‐21.48, P = .013]) were significant risk factors for PTLD, with the latter two factors having a synergistic effect in increasing PTLD risk in a stratified analysis. The final multivariate model in predicting the risk of PTLD, utilizing CMV primary infection, recipient CMV seronegativity, and ACR before PTLD as predictive variables, was statistically significant (likelihood ratio chi square statistic = 25.18, P < .0001 with df = 3).

Conclusions

We report a unique clinicopathologic and risk factor profile in our cohort—early lesion PTLD accounts for the majority and the incidence of monomorphic PTLD remains low. In addition, we show a synergism between CMV naivety and ACR on PTLD risk, a higher prevalence of gastrointestinal manifestations, and a lack of significant association with Epstein‐Barr virus seronegativity.     

The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation in patients with acute myeloid leukemia receiving grafts from unrelated donors

Several studies provided evidence of a consistent antileukemic effect induced by cytomegalovirus (CMV) replication in acute myeloid leukemia (AML) patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), however the use of antithymocyte globulin (ATG) as graft‐versus‐host disease prophylaxis, may potentially abrogate the protective effect of CMV infection. To address this issue, we retrospectively analyzed the risk of relapse in a cohort of 101 patients with AML who received grafts from an unrelated donor after a conditioning regimen including ATG. The cumulative incidence of CMV reactivation, evaluated by RT qPCR, was 59% at 12 months, and 93% of CMV reactivations occurred within the first 100 days post HSCT. The 5‐year cumulative incidence of relapse in patients with CMV reactivation was 29% compared with 37% for patients without CMV reactivation, and the only factor associated with a reduced 5‐year cumulative incidence of relapse was the disease status at HSCT (P < 0.001). In the multivariable model adverse cytogenetics (HR 2.42, 95% CI 1.02‐5.72; P = 0.044) and acute GVHD (HR 3.36, 95% CI 1.32‐8.54; P = 0.011) were independent risk factors for reducing overall survival (OS), while the presence of chronic GVHD was associated with a better OS (HR 0.37, 95% CI 0.15‐0.89; P = 0.027). CMV replication was not an independent risk factor for OS (HR 1.06, 95% CI 0.07‐15.75; P = 0.965). In Conclusion, the results of present study suggest that relapse prevention in patients with AML receiving T‐cell depleted HSCT using ATG do not benefit from CMV reactivation. Am. J. Hematol. 90:E117–E121, 2015. © 2015 Wiley Periodicals, Inc.     

Incidence,etiology, and outcome of pleural effusions in allogeneic hematopoietic stem cell transplantation

Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity?mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 ? 869) post‐HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 ? 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P < 0.001). Overall, pleural effusion is a frequently occurring complication after allogeneic HSCT, adding to morbidity and mortality and hence, early identification is required. Am. J. Hematol. 91:E341–E347, 2016. © 2016 Wiley Periodicals, Inc.     

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.     

Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73–0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66–0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55–0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00–2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72–1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68–1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86–2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70–1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.     

Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study

Introduction and objectivesAcute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting.Patients and methodsWe performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019.ResultsAKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p = 0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p = 0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p < 0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p = 0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p = 0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p = 0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p = 0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p = 0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p = 0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival.ConclusionPatients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.     

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3–6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 10⁹/ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16–0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27–0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15–0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02–0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02–0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.     

Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality

Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.6%) developed BSI. Of the 185 isolates, 68% were Gram-positive cocci, 21% were Gram-negative bacilli (GNR) and 11% were fungi. Type of allogeneic HSCT was an independent risk factor for BSI (hazard ratio (HR) 3.26, 95% confidence interval (CI) 1.50, 7.07, P = 0.01), as was the degree of HLA matching (HR 1.84, 95% CI 1.00, 3.37, P = 0.05). BSI was a significant independent predictor of mortality after HSCT (HR 1.79, 95% CI 1.18, 2.73, P = 0.007), after adjusting for acute graft-versus-host disease (GVHD) and allogeneic HSCT (both predicting death < or = 3 months after HSCT). In contrast to the effects of acute GVHD and allogeneic HSCT, the effect of BSI was evident throughout the post-HSCT period. GNR BSI and vancomycin-resistant enterococcal BSI also were significantly associated with death. We concluded that BSI is a common complication of HSCT associated with increased mortality throughout the post-HSCT period.     

Epidemiology,outcomes, and mortality predictors of invasive mold infections among transplant recipients: a 10‐year,single‐center experience

Background

The epidemiology of invasive mold infections (IMI) in transplant recipients differs based on geography, hosts, preventative strategies, and methods of diagnosis.

Methods

We conducted a retrospective observational study to evaluate the epidemiology of proven and probable IMI, using prior definitions, among all adult hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients in the era of “classic” culture‐based diagnostics (2000–2009). Epidemiology was evaluated before and after an initiative was begun to increase bronchoscopy in HSCT recipients after 2005.

Results

In total, 106 patients with one IMI were identified. Invasive aspergillosis (IA) was the most common IMI (69; 65.1%), followed by mucormycosis (9; 8.5%). The overall rate of IMI (and IA) was 3.5% (2.5%) in allogeneic HSCT recipients. The overall incidence for IMI among lung, kidney, liver, and heart transplant recipients was 49, 2, 11, and 10 per 1000 person‐years, respectively. The observed rate of IMI among human leukocyte antigen‐matched unrelated and haploidentical HSCT recipients increased from 0.6% annually to 3.0% after bronchoscopy initiation (P < 0.05). The 12‐week mortality among allogeneic HSCT, liver, kidney, heart, and lung recipients with IMI was 52.4%, 47.1%, 27.8%, 16.7%, and 9.5%, respectively. Among allogeneic HSCT (odds ratio [OR]: 0.07, P = 0.007) and SOT (OR: 0.22, P = 0.05) recipients with IA, normal platelet count was associated with improved survival. Male gender (OR: 14.4, P = 0.007) and elevated bilirubin (OR: 5.7, P = 0.04) were significant predictors of mortality for allogeneic HSCT and SOT recipients with IA, respectively.

Conclusions

During the era of culture‐based diagnostics, observed rates of IMI were low among all transplants except lung transplant recipients, with relatively higher mortality rates. Diagnostic aggressiveness and host variables impact the reported incidence and outcome of IMI and likely account for institutional variability in multicenter studies. Definitions to standardize diagnoses among SOT recipients are needed.     

Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients

Background. Bacteremias, which are often caused by gram‐negative bacteria, are the most frequently occurring infectious complications after liver transplantation (LT). The aim of this study was to investigate bacteremic incidence, pathogenic spectrum, risk factors for bacteremia due to multidrug resistant (MDR) gram‐negative bacilli, and its impact on mortality after LT. Methods. A cohort analysis of prospectively recorded data was done in 475 LT recipients, who were divided into 3 categories: cases with gram‐negative bacteremia, cases with MDR gram‐negative bacteremia, and cases without bacteremia as controls. Results. In 475 LT recipients, there were 152 (32.0%) patients with gram‐negative bacillus bacteremia in the first 6 months after LT. Out of 152 patients, there were 225 bacteremic episodes, which accounted for 69.7% in a total 323 bacteremic episodes. A total of 190 bacteremic episodes were caused by Stenotrophomonas maltophilia, Enterobacteriaceae, Ochrobactrum anthropi, Pseudomonas, and Acinetobacter baumanii, all of which were the most frequent gram‐negative isolates in this study, and MDR bacilli constituted 56.3%. The most frequent source was intravascular catheters. There were 70 patients with MDR gram‐negative bacillus bacteremia. Independent risk factors for bacteremia due to MDR gram‐negative bacillus were as follows: post‐LT abdominal infection (P<0.0001, odds ratio [OR] 0.066, 95% confidence interval [CI] 0.019–0.226), post‐LT reoperative episodes (P<0.0001, OR 10.505, 95% CI 3.055–36.121), or one or more episodes of acute rejection (P=0.042, OR 4.457, 95% CI 0.988–20.103). In the first 6 months after LT, MDR gram‐negative bacillus bacteremia‐related mortality was significantly higher than that due to antibiotic‐susceptible bacillus (38.6% vs. 14.6%, P<0.001). Conclusion. Post‐LT bacteremias caused by MDR gram‐negative bacilli are common, and associated with allograft acute rejection, post‐LT reoperation, and abdominal infection. The increasing isolates of MDR gram‐negative bacilli pose a great challenge for clinical treatment.     

Cardiovascular risk modification in participants with coronary disease screened by the Kidney Early Evaluation Program

Background: Coronary artery disease (CAD) identifies the need for intensive treatment of risk factors among individuals with chronic kidney disease (CKD), a high‐risk, complex cardiovascular risk state. Methods: An estimated glomerular filtration rate <60 mL/min/1.73 m² or a urine albumin : creatinine ratio (ACR) ≥ 30 mg/g (3.4 mg/mmol) defined CKD. Results: Of 70 454 volunteers screened the mean age was 53.5 ± 15.7 years and 68.3% were female. A total of 5410 (7.7%) had a self‐reported history of CAD; 1295 (1.8%) had a history of prior percutaneous coronary intervention (PCI); and 1124 (1.6%) had a prior history of coronary artery bypass surgery (CABG). Multivariate analysis for the outcome of suboptimal CAD risk management (composite of systolic blood pressure ≥130 mmHg, glucose ≥125 mg/dL (6.9 mmol/L) for diabetics, total cholesterol ≥200 mg/dL (5.2 mmol/L), or current smoking; n= 38 746/53 403, 72.5%) revealed older age (per year) (odds ratio (OR) = 1.04, 95% confidence interval (CI) 1.03–1.04, P < 0.0001), male gender (OR = 1.40, 95% CI 1.34–1.47, P < 0.0001), ACR ≥ 30 mg/g (3.4 mg/mmol) (OR = 1.66, 95% CI 1.55–1.79, P < 0.0001), body mass index (per kg/m²) (OR = 1.06, 95% CI 1.06–1.06, P < 0.0001), CAD without a history of revascularization (OR = 1.14, 95% CI 1.02–1.28, P= 0.02) and care received by a nephrologist (OR = 1.49, 95% CI 1.22–1.83, P < 0.0001) were associated with worse risk factor control. Prior coronary revascularization and being under the care of a cardiologist were not associated with either improved or suboptimal risk factor control. Conclusions: Chronic kidney disease is associated with overall poor rates of CAD risk factor control.