Marie-Chantal Ethier

Defining Bloodstream Infections Related to Central Venous Catheters in Patients With Cancer: A Systematic Review

The objective of this review was to determine whether consistent definitions were used in published studies of bloodstream infections due to central venous catheters in patients with cancer (ie, catheter-related or catheter-associated bloodstream infections). Review of 191 studies reporting catheter-related or catheter-associated bloodstream infections in patients with cancer revealed a lack of uniformity in these definitions. We grouped definitions by type, with 39 articles failing to cite or report a definition. Definitions included those of the Centers for Disease Control and Prevention (n = 39) and the Infectious Diseases Society of America (n = 18). The criteria included in the definitions in studies were also tabulated. Clinical manifestations were frequently included. Definitions used have been highly variable; comparability of risk factors, incidence, management, and outcomes of such infections is difficult to achieve across studies. Future research should focus on development of a common definition of catheter-related and catheter-associated bloodstream infections for both adults and children with cancer.

Association between tumor necrosis factor-α promoter −308 A/g polymorphism and susceptibility to sepsis and sepsis mortality: A systematic review and meta-analysis

Objective:The tumor necrosis factor (TNF)-&agr; promoter −308 A/G polymorphism has been reported to be associated with sepsis with inconsistent results. We conducted a systematic review and meta-analysis to determine whether the TNF-&agr; −308 A/G polymorphism TNF2 (G/A or A/A) confers susceptibility to sepsis or is associated with increased risk of death from sepsis. Data Sources:We performed an electronic search of OVID MEDLINE from 1950 to June 2008 and EMBASE from 1980 to June 2008. Study Selection:From 1935 reviewed study articles, 25 were included based on predefined inclusion criteria. Data Extraction:Two reviewers independently extracted data onto standardized forms. Data Synthesis:An association between development of sepsis and the TNF2 genotype was found in the overall population (odds ratio, 2.15; 95% confidence interval, 1.45–3.19; p < .01). Stratification by ethnicity indicated that the contribution to this observation may be stronger among the Asian population (odds ratio, 3.16; 95% confidence interval, 1.92 to 5.20; p < .01) compared with other ethnicities. There was no association between the TNF2 genotype and mortality from sepsis (odds ratio, 1.48; 95% confidence interval, 0.81 to 2.70; p = .20). However, when stratified for ethnicity, there may be an increased risk for fatal outcomes among Asians (odds ratio, 10.75; 95% confidence interval, 2.98 to 38.78; p < .01). Conclusions:Our systematic review and meta-analysis demonstrates that the TNF2 polymorphism is associated with sepsis. However, TNF2 is not associated with sepsis mortality.

Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis.

The role of leukapheresis and low-dose chemotherapy is unclear in decreasing early mortality in acute myeloid leukemia (AML) patients with hyperleukocytosis. This systematic review was conducted to describe early mortality (deaths during first induction) in patients with AML with an initial white blood count≥100×10(9)L(-1) stratified by the approach to leukapheresis and hydroxyurea/low-dose chemotherapy. Twenty-one studies were included. Weighted mean early deaths rate (20 studies, 1354 patients) was 20.1% (95% confidence interval 15.0-25.1). Neither leukapheresis strategy (p=0.67) nor hydroxyurea/low-dose chemotherapy (p=0.23) influenced the early death rate. Early mortality related to hyperleukocytosis in AML is not influenced by universal or selected use of leukapheresis or hydroxyurea/low-dose chemotherapy.

International variations in infection supportive care practices for paediatric patients with acute myeloid leukaemia

This study described infection‐related supportive care practices amongst centres participating in two large paediatric acute myeloid leukaemia (AML) cooperative groups, Children’s Oncology Group (COG) and Berlin‐Frankfurt‐Muenster (BFM). We surveyed 216 COG and 55 BFM institutions. The overall survey response rate was 83·8%. Antibacterial prophylaxis was more common among BFM (15/46, 32·6%) compared to COG (24/180, 13·3%, P < 0·0001) institutions. Antifungal prophylaxis also was more common among BFM (42/46, 91·3%) compared to COG (137/178, 77·0%, P = 0·03). There were systematic differences in infection‐related supportive care practices. This information may be used to encourage harmonization of supportive care practices and future randomized trials.

Association Between Corticosteroids and Infection, Sepsis, and Infectious Death in Pediatric Acute Myeloid Leukemia (AML): Results From the Canadian Infections in AML Research Group

BACKGROUND Infection continues to be a major problem for children with acute myeloid leukemia (AML). Objectives were to identify factors associated with infection, sepsis, and infectious deaths in children with newly diagnosed AML. METHODS We conducted a retrospective, population-based cohort study that included children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease, or death (whichever occurred first). Consistent trained research associates abstracted all information from each site. RESULTS 341 patients were included. Median age was 7.1 years (interquartile range [IQR], 2.0-13.5) and 29 (8.5%) had Down syndrome. In sum, 26 (7.6%) experienced death as a first event. There were 1277 courses of chemotherapy administered in which sterile site microbiologically documented infection occurred in 313 courses (24.5%). Sepsis and infectious death occurred in 97 (7.6%) and 16 (1.3%) courses, respectively. The median days of corticosteroid administration was 2 per course (IQR, 0-6). In multiple regression analysis, duration of corticosteroid exposure was significantly associated with more microbiologically documented sterile site infection, bacteremia, fungal infection, and sepsis. The only factor significantly associated with infectious death was days of corticosteroid exposure (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P = .001). CONCLUSIONS In pediatric AML, infection, sepsis, and infectious death were associated with duration of corticosteroid exposure. Corticosteroids should be avoided when possible for this population.

Mould-active compared with fluconazole prophylaxis to prevent invasive fungal diseases in cancer patients receiving chemotherapy or haematopoietic stem-cell transplantation: a systematic review and meta-analysis of randomised controlled trials

Background:Objectives were to compare systemic mould-active vs fluconazole prophylaxis in cancer patients receiving chemotherapy or haematopoietic stem cell transplantation (HSCT).Methods:We searched OVID MEDLINE and the Cochrane Central Register of Controlled Trials (1948-August 2011) and EMBASE (1980-August 2011). Randomised controlled trials of mould-active vs fluconazole prophylaxis in cancer or HSCT patients were included. Primary outcome was proven/probable invasive fungal infections (IFI). Analysis was completed by computing relative risks (RRs) using a random-effects model and Mantel–Haenszel method.Results:From 984 reviewed articles, 20 were included in this review. Mould-active compared with fluconazole prophylaxis significantly reduced the number of proven/probable IFI (RR 0.71, 95% CI 0.52 to 0.98; P=0.03). Mould-active prophylaxis also decreased the risk of invasive aspergillosis (IA; RR 0.53, 95% confidence interval (CI) 0.37–0.75; P=0.0004) and IFI-related mortality (RR 0.67, 95% CI 0.47–0.96; P=0.03) but is also associated with an increased risk of adverse events (AEs) leading to antifungal discontinuation (RR 1.95, 95% CI 1.24–3.07; P=0.004). There was no decrease in overall mortality (RR 1.0; 95% CI 0.88–1.13; P=0.96).Conclusion:Mould-active compared with fluconazole prophylaxis significantly reduces proven/probable IFI, IA, and IFI-related mortality in cancer patients receiving chemotherapy or HSCT, but increases AE and does not affect overall mortality.(PROSPERO Registration: CRD420111174)

Lack of clarity in the definition of treatment-related mortality: pediatric acute leukemia and adult acute promyelocytic leukemia as examples

Treatment-related mortality (TRM) is important in acute lymphoblastic leukemia and acute myeloid leukemia (AML); however, little is known about how TRM is defined across trials. Two major problems are related to what constitutes treatment versus disease-related cause of death and to TRM attribution (for example, death because of infection or hemorrhage). To address the former, we conducted a systematic review of randomized therapeutic pediatric acute leukemia and adult/pediatric acute promyelocytic leukemia trials and any study type focused on TRM in pediatric acute leukemia. We described definitions used for TRM. Sixty-six studies were included. Few therapeutic pediatric acute lymphoblastic leukemia studies (2/32, 6.3%) provided definitions for TRM, whereas more therapeutic pediatric AML studies (6/9, 66.7%) provided definitions. There was great heterogeneity in TRM classification. The authors of most studies relied on deaths during induction or in remission to delineate whether a death was TRM. However, 44.4% of therapeutic AML studies used death within a specific time frame to delineate TRM. We suggest that a consistent approach to defining and determining attribution for TRM in acute leukemia is an important future goal. Harmonization of definitions across the age spectrum would allow comparisons between pediatric and adult studies.

Utility of peripheral blood cultures in bacteremic pediatric cancer patients with a central line

PurposeThe utility of peripheral blood cultures in febrile neutropenic children with cancer and central venous catheters (CVC) is controversial. Our primary objective was to describe true bloodstream infections detected only by peripheral culture. Our secondary objectives were to describe true bloodstream infections detected only by CVC culture and to describe probable contaminants detected in both types of blood cultures.MethodsWe included children with cancer who had peripheral and CVC cultures obtained on the same day in which at least one culture was positive. Only cultures obtained prior to the initiation of broad-spectrum antibiotics were included. We defined true bloodstream infections due to common contaminants (such as coagulase-negative Staphylococcus) as occurring if multiple cultures were positive for the same organism or if sepsis was present.ResultsBetween January 2002 and July 2007, 318 episodes of bloodstream infection from 224 children were included. Of these, 228/318 (71.7%) were classified as true bloodstream infections while 90/318 (28.3%) were classified as contaminants. Importantly, 28/228 (12.3%) true bloodstream infections were detected only in peripheral culture while 85/228 (37.3%) true bloodstream infections were detected only by CVC cultures. Contaminants were identified in peripheral culture in 45/318 (14.2%) of episodes and in CVC culture in 45/318 (14.2%) episodes.ConclusionsTrue bloodstream infections frequently are only detected in the peripheral culture. These data support continuation of the practice of routine peripheral cultures in addition to CVC cultures at the onset of fever for children with cancer who are not already receiving broad-spectrum antibiotics.

Low Socioeconomic Status Is Associated with Prolonged Times to Assessment and Treatment, Sepsis and Infectious Death in Pediatric Fever in El Salvador

Background Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. Method This prospective cohort study included children aged 0–16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. Findings Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0–20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0–3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09–8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03–1.81; P = 0.031) and in families with an annual household income <US

Complementary and alternative medicine use in pediatric cancer reported during palliative phase of disease

2,000 (OR 13.90, 95% CI 1.62–119.10; P = 0.016). Interpretation Illiteracy, poverty, and longer travel times are associated with delays in assessment and treatment of fever and with sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families and staying at a nearby guest house during periods of neutropenia may decrease sepsis and infectious mortality.