Infection-related Mortality In Patients Research Articles

#1956 Effect of hemodialysis modalities on infection-related mortality

Abstract Background and Aims A growing body of evidence have suggested hemodiafiltration (HDF) provide survival benefit for dialysis patients. HDF may improve immune modulation with enhanced clearance of azotemic toxins, compared to high-flux hemodialysis (HD). We therefore assess the effect of dialysis modalities on infection-related mortality in patients treated in real-world settings. Method We conducted a retrospective cohort-study based on 85,117 adult haemodialysis (HD) patients who were treated in EMEA NephroCare Clinics between January 1, 2019 and December 31, 2022. All patients’ data were extracted from the European Clinical Database (EuCliD®), including mortality from any infection, viral infection, and COVID-19 infection. The definition of mortality cause is based on ICD-10 codes. Any infection related mortality includes a broad range of infection disease types, such as viral, bacterial, parasitic, and fungal infections. The associations between dialysis modality and infection-related mortality were analyzed by multivariable Cox regression models, with both dialysis modality and COVID-19 infection as time-dependent covariates. To account for potential impact of difference in patients’ characteristics, we adjusted for multiple confounding factors. Competing risk analyses with death from non-infection as the competing event were performed by cause-specific and Fine-Gray subdistribution hazard models. Results At baseline 45.0% patients were treated with HDF, which changed to 52.6% by the end of follow-up. Of all HDF treatments in post-dilution mode (account for 98.4% HDF treatments) during follow-up, the average convection volume was 25.7 liters (median [interquartile range], 25.8 [23.9–28.0]). Patients treated with HDF at baseline were younger, with less comorbidities and longer dialysis vintage, compared to patients with HD (Table 1). During a median follow-up of 22.6 months, death from any infection occurred among 6.9% patients, of which 40.1% died from COVID-19 infection. Compared to HD, HDF was associated with a reduced risk of dying from any infection (hazard ratio [HR], 0.89 [95% CI, 0.82–0.97]), which however disappeared if excluding death from COVID-19 infection (Table 2). Similar pattern was also observed for death from viral infection. Association of HDF with death from COVID-19 infection persisted after controlling for multiple confounders (HR, 0.81 [95% CI, 0.71–0.93]). Similar results yielded from competing risk analyses. Conclusion In this large, unselected patient population, the beneficial effect of HDF for infection-related mortality was confined to mortality from COVID-19 infection. Further studies are needed to unravel the relation between dialysis modalities and death from different types of infection.

Trends and disparities in cardiac implantable electronic device infection-related mortality in the United States.

We performed a cross-sectional study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyze the trends in cardiac implantable electronic device (CIED) infection-related mortality from 1999 to 2020. We analyzed the death certificate data from the CDC WONDER database from 1999 to 2020 for CIED infections in the US population aged ≥25 years usingInternational Classification of Diseases, Tenth Revision(ICD-10) codes, listed as the underlying or contributing cause of death. Age-adjusted mortality rates (AAMR) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population. To assess annual mortality trends, we employed the Joinpoint regression model, calculating the annual percent change (APC) in AAMR and corresponding 95% CIs. Overall, there was an observed declining trend in AAMRs related to CIED infection-related mortality. Males accounted for 55% of the total deaths, with persistently higher AAMRs compared to females over the study duration. Both males and females had an overall decreasing trend in AAMRs throughout the study duration. On race/ethnicity stratified analysis, non-Hispanic (NH) Blacks exhibited the highest overall AAMR, followed by NH American Indians or Alaska Natives, NH Whites, Hispanic or Latinos, and NH Asian or Pacific Islanders. On a stratified analysis based on region, the South region had the highest overall AAMR, followed by the Midwest, West, and Northeast regions. Our study demonstrates a significant decline in CIED infection-related mortality in patients over the last two decades. Notable gender, racial/ethnic, and regional differences exist in the rates of mortality related to CIED infections.

Risk factors for serious infections and infection-related mortality in patients with microscopic polyangiitis: Multicentre REVEAL cohort study.

Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

Serum alkaline phosphatase and infection-related mortality in hemodialysis patients: ten-year outcomes of the Q-cohort study.

High serum alkaline phosphatase (ALP) levels are associated with excess all-cause and cardiovascular mortality in patients undergoing hemodialysis (HD). However, the long-term relationship between serum ALP levels and infection-related mortality remains unclear. A total of 3502 maintenance HD patients were registered in the Q-Cohort Study, an observational cohort study in Japan. The primary outcome was infection-related mortality during a 10-year follow-up period. The covariate of interest was serum ALP levels at baseline. The association between serum ALP levels and infection-related mortality was calculated using a Cox proportional hazards model and a Fine-Gray subdistribution hazards model with non-infection-related death as a competing risk. During the follow-up period, 446 patients died of infection. According to their baseline serum ALP levels, the patients were categorized into sex-specific quartiles (Q1-Q4). Compared with patients in the lowest serum ALP quartile (Q1), those in the highest quartile (Q4) had a significantly higher multivariable-adjusted hazard ratio (HR) of 1.70 [95% confidence interval (CI) 1.24-2.32] for infection-related mortality. Furthermore, the HR for every 50U/L increase in serum ALP levels was 1.24 (95% CI 1.12-1.36) for infection-related mortality. These associations remained consistent in the competing risk model: subdistribution HR, 1.47; 95% CI 1.07-2.03 for Q4 compared with Q1. Higher serum ALP levels were significantly associated with a higher risk of infection-related mortality in patients undergoing HD.

Postoperative infection-related mortality and lymphocyte-to-C-reactive protein ratio in patients undergoing on-pump cardiac surgery: a novel predictor of mortality?

This study aims to investigate the relationship between postoperative infection-related mortality and lymphocyte-to-C-reactive protein ratio (LCR), a newly defined parameter with the combination of inflammatory and immune parameters, in patients undergoing cardiac surgery. Between January 2016 and November 2021, 236 patients who underwent on-pomp cardiac surgery with median sternotomy and developed postoperative infection were analyzed retrospectively. Patients were divided into six groups according to the types of postoperative infection. Preoperative, perioperative, and postoperative variables of the patient groups were compared, and factors affecting postoperative mortality were evaluated. The mortality rate in the patient group we included in the study was 22.9%. Mortality rates did not differ significantly between the infection groups. However, when the LCR value was evaluated between the groups, there was a statistically significant difference (p<0.001). The preoperative LCR cut-off value, which predicts postoperative infection-related mortality, was determined as 133.46 (area under the curve (AUC): 0.607, p=0.017, 48.1% sensitivity, and 47.8% specificity). In the multivariate analysis, postoperative cerebrovascular event (OR: 78.365, 95% CI: 12.367-496.547, p<0.001) and Intensive Care Unit (ICU) stay (odds ratio (OR): 1.136, 95% confidence interval (CI): 1.004-1.284, p=0.042) variables were found to be independent predictive factors of postoperative infection-related mortality in the model. There was no positive differentiation of the type of infection in predicting mortality. The calculated LCR value is a novel and remarkable parameter in estimating postoperative infection-related mortality in patients undergoing cardiac surgery.

X-Linked Agammaglobulinemia: Infection Frequency and Infection-Related Mortality in the USIDNET Registry.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. Among the 231 XLA patients enrolled in the Registry, respiratory infections (N = 203, 88%) were the most commonly reported. Among those deceased (N = 20) where cause of death was known (N = 17), mortality was attributed to infection in most (N = 12, 71%). Chronic lung disease, often a consequence of repeated lower respiratory tract infection (LRTI), was also a frequent complication associated with mortality (N = 9, 53%). Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.5–3.3] vs. median 3.0 [IQR 1.0–5.0], p = 0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.5–5.0] vs. median 2.7 [IQR 1.6–6.0], p = 0.04). Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.4–2.4] vs. median 2.8 [IQR 1.0–5.4], p = 0.0006). For every year increase in age at start of therapy, the odds of experiencing a LRTI was 1.216 (OR 1.216, 95% CI 1.048–1.411, p = 0.01). Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

The survival analysis of tunnel-cuffed central venous catheter versus arteriovenous hemodialysis access among elderly patients: A retrospective single center study

BackgroundThere is currently a controversy for the optimal vascular access option in the elderly, regarding their multiple comorbidities and life expectancies. Our study aimed to compare the survival of tunneled cuff venous catheter (CVC) and arteriovenous access (AV access) in elderly patients. MethodsA retrospective cohort study was performed by electronic medical record review. All hemodialysis patients aged 65 years and over who firstly initiated dialysis from January 1, 2012 to December 31, 2016 at Siriraj hospital, Thailand, were included. The primary outcomes are to compare a 2-year period of survival between CVC and AV access in terms of abandonment, death, and combined outcome. Propensity score covariate and Charlson Comorbidity Score (CCI) were used for multivariable analysis adjustment. ResultsA total of 359 patients were included; 216 (60.2%) patients had initiated hemodialysis via CVC while the rest used AV access. The patients’ average ages were 76.7 ± 7.0 and 74.0 ± 5.8 years (p-value<0.001) in the CVC and AV access group, respectively. The 2-year mortality rates of CVC and AV access groups were 24.1% and 15.4%, respectively (p-value = 0.038). Multivariable analyses showed that the adjusted hazard ratio (aHR) of combined endpoints, i.e., vascular access abandonment and death, was statistically different only in the CCI-adjusted model (aHR = 0.68, 95% CI: 0.46–0.99). Mortality from infection cause was more common in the CVC group than the AV access group. ConclusionCVC access maybe considers an alternative option for frail elderly patients. However, the patient selection is a crucial issue, given higher infection-related mortality in patients using CVC.

Low parathyroid hormone level predicts infection-related mortality in incident dialysis patients: a prospective cohort study.

Background/AimsParathyroid hormone (PTH) is an important factor influencing immunologic dysfunction, but the effect of PTH level on infection-related outcomes remains unclear in incident dialysis.MethodsWe evaluated a multicenter prospective cohort study of 1,771 incident dialysis patients (1,260 hemodialysis and 511 peritoneal dialysis) in Korea. Patients were divided into three groups based on serum intact PTH (iPTH) level. The primary outcomes were all-cause and infection-related mortality and multivariate Cox regression analysis was performed to evaluate the role of iPTH in all-cause and infection-related mortality.ResultsDuring the follow-up period of 27.3 months, 175 patients (9.9%) died, and infection-related death represented 20% of all-cause mortality. Both all-cause mortality and infection-related mortality rates (p < 0.001 and p = 0.003, by logrank) were markedly higher in patients with serum iPTH < 150 pg/mL than in the other groups. Multivariate Cox regression analysis revealed that patients with serum iPTH < 150 pg/mL remained at higher risk for infection-related mortality than patients in the target range of 150 ≤ iPTH < 300 pg/mL, after adjusting for confounding variables (hazard ratio [HR], 2.52; 95% confidence interval, 1.06 to 5.99; p = 0.04). The HR of infection-related mortality in patients with serum iPTH < 150 pg/mL was significantly higher in patients with low serum phosphorus, low Ca × P product, low serum alkaline phosphatase and those older than 65 years.ConclusionsLow serum iPTH level is an independent predictor of infection-related mortality in incident dialysis patients.

Development of a risk prediction model for infection-related mortality in patients undergoing peritoneal dialysis.

BackgroundAssessment of infection-related mortality remains inadequate in patients undergoing peritoneal dialysis. This study was performed to develop a risk model for predicting the 2-year infection-related mortality risk in patients undergoing peritoneal dialysis.MethodsThe study cohort comprised 606 patients who started and continued peritoneal dialysis for 90 at least days and was drawn from the Fukuoka Peritoneal Dialysis Database Registry Study in Japan. The patients were registered from 1 January 2006 to 31 December 2016 and followed up until 31 December 2017. To generate a prediction rule, the score for each variable was weighted by the regression coefficients calculated using a Cox proportional hazard model adjusted by risk factors for infection-related mortality, including patient characteristics, comorbidities, and laboratory data.ResultsDuring the follow-up period (median, 2.2 years), 138 patients died; 58 of them of infectious disease. The final model for infection-related mortality comprises six factors: age, sex, serum albumin, serum creatinine, total cholesterol, and weekly renal Kt/V. The incidence of infection-related mortality increased linearly with increasing total risk score (P for trend <0.001). Furthermore, the prediction model showed adequate discrimination (c-statistic = 0.79 [0.72–0.86]) and calibration (Hosmer–Lemeshow test, P = 0.47).ConclusionIn this study, we developed a new model using clinical measures for predicting infection-related mortality in patients undergoing peritoneal dialysis.

Predictors of one-year all-cause mortality and infection-related mortality in patients with Staphylococcus aureus bacteraemia

Objectives: Staphylococcus aureus bacteraemia (SAB) is a common infection associated with significant short-term mortality. Little is known about long-term prognosis. The aim of this study was to determine one-year all-cause mortality and infection-related mortality and associated predictors.Methods: Data from 303 consecutive patients with SAB were prospectively collected from March 2011 to February 2014. All patients were followed one year or until death.Results: One-year all-cause- and infection-related mortality were 36.7% and 20.8%, respectively. For all-cause mortality, in multivariable logistic regression analysis, age 70–79 years (OR 3.9; 95% CI 1.7–9.1; p = .001), Charlson Comorbidity index ≥3 (OR 6.9; 95% CI 2.7–17.3; p < .001), healthcare-associated infection (OR 2.3; 95% CI 1.1–4.9; p = .03) and severe sepsis (OR 3.6; 95% CI 1.8–7.1; p < .001) were independent predictors of outcome. For infection-related mortality, the predictors were similar, except for healthcare-associated infection that lost significance. The vast majority (89%) of infection-related deaths occurred within 30 days.Conclusions: This study demonstrates additional significant all-cause mortality in patients with SAB beyond 30 days to one year, mainly driven by high age and comorbidity. As a result, SAB can be considered an indirect marker of high risk of death in these patients. Follow-up beyond 30 days does not add significant information with respect to infection-related mortality.

Association of geriatric nutritional risk index with infection-related mortality in patients undergoing hemodialysis: The Q-Cohort Study

The geriatric nutritional risk index (GNRI) is a simple but useful nutritional marker for all-cause mortality and cardiovascular mortality in patients undergoing hemodialysis (HD). However, whether the GNRI can predict infection-related mortality in patients undergoing HD remains unclear, and there is insufficient evidence regarding whether the GNRI improves the predictive value for risk assessment beyond the existing conventional nutritional markers. Here, we investigated the association between the GNRI and infection-related mortality in patients undergoing HD and evaluated the predictive value of GNRI. A prospective cohort study was performed on a total of 3436 Japanese HD patients aged ≥18 years. Patients were divided into four groups by quartiles of GNRI: (Quartile 1 [Q1], >100.2; Q2, 95.9-100.2; Q3, 90.8-95.8; Q4, <90.8). We estimated the relationship between GNRI and all-cause mortality and infection-related mortality using a Cox proportional hazards model. To assess the additional predictive value of the GNRI in risk assessment, we compared the c-statistic, net reclassification improvement, and integrated discrimination improvement among serum albumin, serum creatinine, and the GNRI. During follow-up period (median, 4.0 years), a total of 564 patients died; 120 of these patients died of infectious disease. All-cause mortality and infection-related mortality increased linearly with lower GNRI levels. After adjusting for confounding risk factors, the GNRI was an independent predictor of infection-related mortality as well as all-cause mortality (hazard ratio [HR], 5.89; 95% confidence interval [CI], 2.85-13.8; P<0.001 for Q4 vs. Q1, HR, 2.62; 95% CI, 1.23-6.24; P=0.01 for Q3 vs. Q1). Additionally, when the GNRI was incorporated into a model with potential risk factors instead of serum albumin, the c-statistic increased significantly (0.811 vs. 0.821, P=0.03), and the net reclassification improvement and integrated discrimination improvement was 0.26 (P=0.005) and 0.005 (P=0.01). This association was more apparent in the older patients (0.739 vs. 0.760, P=0.02) than in the younger patients (0.916 vs. 0.912, P=0.35). Similar results were observed between serum creatinine and the GNRI, but the difference did not reach statistical significance. Lower GNRI levels are an independent risk factor for infection-related mortality in patients undergoing HD. Moreover, addition of the GNRI to models with standard risk factors significantly improves the predictive ability of infection-related mortality, especially in older patients.

Risk of infections in patients with gout: a population-based cohort study

To investigate the risk of various types of infections (pneumonia and urinary tract infection (UTI)), and infection-related mortality in patients with gout compared with population-based controls. A retrospective cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD). All patients with a first diagnosis of gout and aged >40 years between January 1987-July 2014, were included and matched with up to two controls. Time-varying Cox proportional hazards models were used to estimate the risk of infections and mortality. 131,565 patients and 252,763 controls (mean age: 64 years, 74% males, mean follow-up of 6.7 years) were included in the full cohort. After full statistical adjustment, the risk of pneumonia was increased (adj. HR 1.27, 95% CI 1.18 to 1.36), while the risk of UTI (adj. HR 0.99, 95% CI 0.97 to 1.01) was similar in patients compared to controls. No differences between patients and controls were observed for infection-related mortality due to pneumonia (adj. HR 1.03, 95% CI 0.93 to 1.14) or UTI (adj. HR 1.16, 95% CI 0.98 to 1.37). In conclusion, patients with gout did not have decreased risks of pneumonia, UTI or infection-related mortality compared to population-based controls.

High Infection-Related Mortality in Pediatric Acute Myeloid Leukemia without Preventive Antibiotics and Antifungals: Retrospective Cohort Study of a Single Center from a Middle-Income Country.

Objective:This study aimed to evaluate infection-related mortality in patients with acute myeloid leukemia (AML) treated without preventive antibiotics and antifungals in a middle-income country.Materials and Methods:Infection-related mortality was evaluated retrospectively in 49 pediatric patients.Results:A total of 173 chemotherapy courses were administered as first-line chemotherapy. Four patients died during induction: one patient due to intracranial bleeding, two patients due to typhlitis, and one patient due to invasive fungal infection with pulmonary vascular invasion and massive bleeding. Another two patients died with resistant disease. During consolidation there were four infection-related deaths and one death due to cardiotoxicity. In first-line chemotherapy mortality was 22% (11/49); infection-related mortality was 14% (7/49). Event-free survival and overall survival at 6 years were 42.9% and 61.2% (95% CI: 44-76 and 66-99 months), respectively.Conclusion:Due to considerable infection-related deaths, antibacterial and mold-active antifungal prophylaxis may be tried during neutropenic periods in pediatric AML.

Patterns of infection and infection-related mortality in patients with steroid-refractory acute graft versus host disease.

This study aimed to characterize the incidence, etiology and outcome of infectious episodes in patients with steroid refractory acute GvHD (SR-GvHD). The cohort included 127 adults treated with inolimomab (77%) or etanercept (23%) owing to acute 2-4 SR-GvHD, with a response rate of 43% on day +30 and a 4-year survival of 15%. The 1-year cumulative incidences of bacterial, CMV and invasive fungal infection were 74%, 65% and 14%, respectively. A high rate (37%) of enterococcal infections was observed. Twenty patients (15.7%) developed BK virus-hemorrhagic cystitis and five percent had an EBV reactivation with only one case of PTLD. One-third of long-term survivors developed pneumonia by a community respiratory virus and/or encapsulated bacteria, mostly associated with chronic GvHD. Infections were an important cause of non-relapse mortality, with a 4-year incidence of 46%. In multivariate analysis, use of rituximab in the 6 months before SCT (hazard ratio; HR 4.2; 95% confidence interval; CI 1.1-16.3), severe infection before SR-GvHD onset (HR 5.8; 95% CI 1.3-26.3) and a baseline C-reactive protein >15 UI/mL (HR 2.9; 95% CI 1.1-8.5) were associated with infection-related mortality. High rates of opportunistic infections with remarkable mortality warrant further efforts to optimize long-term outcomes after SR-GvHD.

Clinical Efficacy of Polymyxin Monotherapy versus Nonvalidated Polymyxin Combination Therapy versus Validated Polymyxin Combination Therapy in Extensively Drug-Resistant Gram-Negative Bacillus Infections.

Polymyxins have emerged as a last-resort treatment of extensively drug-resistant (XDR) Gram-negative Bacillus (GNB) infections, which present a growing threat. Individualized polymyxin-based antibiotic combinations selected on the basis of the results of in vitro combination testing may be required to optimize therapy. A retrospective cohort study of hospitalized patients receiving polymyxins for XDR GNB infections from 2009 to 2014 was conducted to compare the treatment outcomes between patients receiving polymyxin monotherapy (MT), nonvalidated polymyxin combination therapy (NVCT), and in vitro combination testing-validated polymyxin combination therapy (VCT). The primary and secondary outcomes were infection-related mortality and microbiological eradication, respectively. Adverse drug reactions (ADRs) between treatment groups were assessed. A total of 291 patients (patients receiving MT, n = 58; patients receiving NVCT, n = 203; patients receiving VCT, n = 30) were included. The overall infection-related mortality rate was 23.0% (67 patients). In the multivariable analysis, treatment of XDR GNB infections with MT (adjusted odds ratio [aOR], 8.49; 95% confidence interval [CI], 1.56 to 46.05) and NVCT (aOR, 5.75; 95% CI, 1.25 to 25.73) was associated with an increased risk of infection-related mortality compared to that with treatment with VCT. A higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score (aOR, 1.14; 95% CI 1.07 to 1.21) and a higher Charlson comorbidity index (aOR, 1.28; 95% CI, 1.11 to 1.47) were also independently associated with an increased risk of infection-related mortality. No increase in the incidence of ADRs was observed in the VCT group. The use of an individualized antibiotic combination which was selected on the basis of the results of in vitro combination testing was associated with significantly lower rates of infection-related mortality in patients with XDR GNB infections. Future prospective randomized studies will be required to validate these findings.

Free thyroxine level as an independent predictor of infection-related mortality in patients on peritoneal dialysis: a prospective multicenter cohort study.

BackgroundPrevious studies have reported the relationship between thyroid hormone levels and mortality in dialysis patients. However, little is known about the association of free thyroxine (fT4) and mortality in patients on peritoneal dialysis (PD). This study investigated the association between basal and annual variation in fT4 level and mortality in PD patients.MethodsPatients on maintenance PD were enrolled from a prospective multicenter cohort study in Korea; their serum triiodothyronine, fT4, and thyroid-stimulating hormone levels were measured 12 months apart. Patients with overt thyroid disease and those receiving thyroid hormone replacement therapy were excluded from the analysis. Patients were divided into two groups based on the median levels of fT4. The differences of all-cause, infection-related, and cardiovascular mortalities were analyzed between the two groups. The association of basal levels and annual variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models.ResultsAmong 235 PD patients, 31 (13.2%) deaths occurred during the mean follow-up period of 24 months. Infection (38.7%) was the most common cause of death. Lower basal fT4 levels were an independent predictor of all-cause and infection-related death (hazard ratio [HR] = 2.74, 95% confidence interval [CI] 1.27–5.90, P = 0.01, and HR = 6.33, 95% CI 1.16–34.64, P = 0.03, respectively). Longitudinally, patients with persistently lower fT4 levels during the 12-month period had significantly higher all-cause mortality than those with persistently higher levels (HR = 3.30, 95% CI 1.15–9.41, P = 0.03). The area under the receiver operating characteristic curve of fT4 for predicting all-cause and infection-related mortality was 0.60 and 0.68, respectively.ConclusionsfT4 level is an independent predictor of mortality and is especially attributable to infection in PD patients. This predictor was consistent when considering both baseline measurements and annual variation patterns. Close attention to infection in PD patients with relatively lower fT4 levels should be considered.

The reduction of post-cardiac surgery infections by statins: solid evidence?

The reduction of post-cardiac surgery infections by statins: solid evidence?

Eradication of Pulmonary Aspergillosis in an Adolescent Patient Undergoing Three Allogeneic Stem Cell Transplantations for Acute Lymphoblastic Leukemia

Systemic fungal infections are a major cause of infection-related mortality in patients with hematologic malignancies. This report addresses the case of an adolescent patient with acute lymphoblastic leukemia who underwent three allogeneic hematopoietic stem cell transplantations and developed pulmonary aspergillosis. Combination therapy with liposomal amphotericin B (L-AmB, 3 mg/kg bw/day) and caspofungin (CAS, 50 mg/day) during the first allogeneic hematopoietic stem cell transplantation (HSCT) improved the pulmonary situation. After shifting the antifungal combination therapy to oral voriconazole (2 × 200 mg/day) and CAS, a new pulmonal lesion occurred alongside the improvements in the existing pulmonary aspergillosis. An antifungal combination during a second HSCT with L-AmB (3 mg/kg bw/day) and CAS showed an improvement in the pulmonary aspergillosis. A combination therapy with CAS and L-AmB (1 mg/kg bw/day) during the third HSCT led once again to progress the pulmonary aspergillosis, after increasing the L-AMB to 3 mg/kg bw/day for recovery. The presented case provides an example of how, despite severe immunosuppression, a combination of antifungal drugs administered intravenously at therapeutic dosages may be more efficient than either intravenous monotherapy or combinations of intravenous and oral antifungals in selecting pediatric and adolescent patients with proven fungal infections.

Overall survival and fungal infection-related mortality in patients with invasive fungal infection and neutropenia after myelosuppressive chemotherapy in a tertiary care centre from 1995 to 2006

ObjectivesInvasive fungal infections (IFIs) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for haematological malignancies. The present study investigates the overall survival (OS), infection-related mortality and changes in treatment of IFIs in our department from 1995 until 2006.MethodsOutcomes of all chemotherapy courses were retrospectively evaluated using a standard questionnaire. Modified EORTC/MSG criteria for IFIs were applied: a positive PCR result for Aspergillus spp. in bronchoalveolar lavage was also defined as probable IFI.ResultsIn total, 1693 chemotherapy courses in 592 patients were evaluated. Sixty-three percent of chemotherapy courses were given to treat acute myeloid leukaemia, with the rest for acute lymphoblastic leukaemia or aggressive lymphoma. IFIs were observed in 139/592 patients [23.5%, 95% confidence interval (CI) 20%–27%] and in 149/1693 courses (8.8%, 95% CI 8%–10%). IFI-related mortality was 56.9% in 1995–2001 and 28.6% in 2002–06, P < 0.001. Accordingly, median OS in patients with IFI increased: 54 days (95% CI 26–82 days) in 1995–2001 versus 229 days (95% CI 35–423 days) in 2002–06, P = 0.001. By multivariate analysis, factors predictive for better OS were controlled disease after chemotherapy [hazard ratio (HR) 0.228, P < 0.001], possible IFI (in contrast to proven/probable IFI, HR 0.537, P = 0.005), age <60 years (HR 0.583, P = 0.008), time period 2002–06 (HR 0.612, P = 0.021) and use of novel antifungals (HR 0.589, P = 0.033).ConclusionsCompared with 1995–2001, IFI-related mortality decreased and OS in patients with IFI increased significantly in recent years. Improved OS was associated with controlled haematological disease, certainty of IFI diagnosis (possible), younger age, time period 2002–06 and the use of novel antifungals.

Prevention of febrile neutropenia: use of prophylactic antibiotics

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated.