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Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia
Abstract
The purpose of the study was to assess the risk of first-time bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL treated at 3 pediatric centers in Denmark between 2008 and 2014. A total of 136 patients were followed from initial CVC placement until first BSI, CVC removal, death, or day 28, whichever occurred first. Thirty-nine BSIs were detected, of which 67% were gram-positive infections, and 59% met the criteria for being CVC associated. The 28-day cumulative incidence of BSI was similar in 77 patients with a nontunneled CVC (28%; 95% confidence interval, 19%-40%) and in 59 patients with a tunneled CVC with external lines (TE) (33%; 95% confidence interval, 23%-47%). Subgroup analyses showed that gram-negative blood isolates occurred more frequently in patients with a TE, and that lower incidences of BSI were detected in patients older than 9 years with a TE, and in patients with T-ALL. It is concluded that the type of CVC inserted at diagnosis has no impact upon the risk of BSI in patients with ALL undergoing induction therapy.
... The incidence of bacteraemia around 30% in this study corresponds to the incidence of bloodstream infections (BSI) previously reported in Denmark during NOPHO ALL-2008 or earlier NOPHO induction protocols with similar trimethoprim-sulfamethoxazole prophylaxis. 25,26 The incidence of bacteraemia or BSI during ALL induction treatment has been reported between 10% and 45% in other studies from high-income countries. 3,[27][28][29] Nevertheless, comparisons are limited F I G U R E 2 Citrulline levels in patients with and without bacteraemia during induction treatment. ...
... The majority of microorganisms isolated in blood cultures were gram-positive bacteria, which is in line with previous studies in children with ALL receiving induction treatment 25,26,28,29 and in paediatric oncological patients in general. 37 42 Therefore, some of the CoNS bacteraemia in our study may have been caused by translocation of these bacteria through the damaged oral or intestinal mucosa. ...
... Spearman's rank correlation coefficients r and P-values are shown in the legend by differences in chemotherapy protocols, antimicrobial prophylaxis regimens and definitions of reported outcomes. In our study, bacteraemia occurred after a median of 2 weeks from start of chemotherapy, as reported by other studies in ALL induction treatment,26,28,29 coinciding with the time point of maximum enterocyte loss and neutropaenia. Nevertheless, plasma citrulline level on day 15 was significantly lower in patients with bacteraemia compared to patients without, while ANC did not differ significantly between the two groups.Moreover, nearly all bacteraemia episodes occurred among patients experiencing a drop in citrulline level during the first 2 weeks of treatment. ...
Background: Systemic infections are amajor cause of morbidity in children with acute
lymphoblastic leukaemia (ALL). However, identification of patients at increased risk is
still a challenge. Knowing that both neutropaenia and gastrointestinal toxicity are risk
factors for bacteraemia, we aimed at comparing absolute neutrophil counts (ANC) and
plasma citrulline levels (indicating enterocyte loss) in children with ALL with and without
bacteraemia during induction treatment.
Procedure:We prospectively included 61 children with ALL treated according to the
Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol.
ANC and plasma C-reactive protein (CRP) were measured on treatment days 1, 8,
15, 22 and 29. Plasma citrulline was measured on days 1, 8, 15 and 29. Bacteraemia
episodes during induction treatment were recorded retrospectively.
Results: Nineteen of sixty-one (31%) patients experienced bacteraemia occurring on
median day 13 (range 5-20). Patients with bacteraemia during induction treatment
had lower citrulline level on day 15 (P < .01) compared to patients without bacteraemia,
indicating more severe enterocyte loss. Nevertheless, ANC was similar in the
two patient groups on days 8 and 15. CRP was negatively correlated with same-day
citrulline (P < .03 for all) and ANC (P < .04 for all).
Conclusions: During chemotherapy-induced neutropaenia, plasma citrulline may help
identify patients at increased risk of bacteraemia.
... As a result of this decreased favorability, placement of central lines with subcutaneous tunnel have been less studied in the pediatric burn patient population. Many studies have evaluated the use of central lines with subcutaneous tunnel in pediatric patients with hematological malignancies since these patients often require long-term venous access for administration of antineoplastic drugs, 3,4 but no studies to date have specifically evaluated the use of tunneled central venous catheterization in pediatric burn patients. ...
Introduction: Pediatric patients with severe burns often require long-term venous access over the course of their recovery. The need for long-term venous access in these critically ill patients often necessitates the placement of a central venous catheter (CVC). Many techniques exist for the establishment of a CVC in pediatric burn patients, and each technique poses its own set of inherent risks. No studies to date have clearly delineated the risk associated with tunneled central venous catheterization in the pediatric burn patient population. The primary aim of this study was to evaluate the use of tunneled CVCs in pediatric burn patients at the University Medical Center Hospital in Lubbock, Texas. Methods: To evaluate this method of central venous catheterization, we retrospectively reviewed the charts of pediatric burn patients who received a tunneled CVC to determine the incidence of specific complications associated with this catheterization technique. We present our findings here in a case series format. Results: Our initial search of patient charts yielded 86 potential candidates for inclusion in the study. After reviewing each chart, 26 pediatric patients were found to have received a CVC. Of these 26 patients, five met all of the inclusion criteria of our study. In these five patients, eight tunneled CVCs were placed. The average age of the patients in this series at the time of their respective burn injuries was 3.9 years old. Mean percent TBSA involvement was 38% with an average length of stay totaling 64.6 days. The average dwell time of the tunneled CVCs in this series was 28 days, and our analysis of the data revealed one tunneled catheterrelated infection and one hemodynamic complication. Conclusions: Overall, our data show that placement of long-term tunneled CVCs in pediatric burn patients appears to be a relatively safe practice. However, our small sample size warrants more investigation into this topic.Keywords: pediatrics, burns, central vein catheters
... 6 The current data on tunneled catheter use in children is limited, as previous studies mainly focus on hematooncology or intensive care unit (ICU) patients. Factors such as younger age, 7,8 underlying chronic medical condition, 7,9 parenteral nutrition, 10 hematopoietic stem cell transplantation, 11,12 neutropenia, 12 duration of hospitalization, 13 multiple lumen, 5,14 non-totally implanted catheters, 11,15 access frequency, 1,4,5 and non-aseptic techniques 2,16 have been shown to increase the risk of catheter-related infections. Recent studies in children have reported CLABSI rates between 1.38 and 5.05 per 1,000 catheter days for tunneled catheters. ...
Background:
Central line-associated bloodstream infections (CLABSIs) are among the most common complications of central venous catheters (CVCs). The aim of this study was to examine the epidemiology of CLABSIs in tunneled CVCs and analyze their risk factors in a general pediatric population.
Methods:
Children with a tunneled CVC inserted at the University Children's Hospital Zürich between January 2009 and December 2015 were eligible for the study. The influence of CVC dwell time on the risk of CLABSI was examined using life tables. Hazard ratios (HRs) for CLABSIs were analyzed using Cox regression for age and diagnosis with cluster robust standard errors.
Results:
Fifty-five CLABSIs were observed in 193 patients with 284 tunneled CVCs. Overall, CVCs in children with gastrointestinal disorders and in children 2 to 5 years of age showed the highest incidence rates of 6.06 and 5.85 CLABSIs per 1,000 catheter days, respectively, during the first 90 days after placement. Gastrointestinal disease (HR, 3.89; 95% CI, 2.19-6.90; P < .001) and age 2 to 5 years (HR, 2.48; 95% CI, 1.45-4.22; P = .001) were identified as independent risk factors for CLABSI. In children without gastrointestinal disease, tunneled CVCs showed an increasing risk of CLABSI after a dwell time of 90 days.
Conclusions:
The need for tunneled CVCs requires the evaluation of targeted CLABSI prevention measures, especially in young children with underlying gastrointestinal disease.
... However, the incidence of positive microbiological detection by BC tests has been low. Importantly, the spectrum of pathogens detected by the BC test has changed with the time depending on various factors, such as types of prophylactic agents, the usage of either a Central Venous Catheter (CVC) or external lines, BSI recurrence, and types of treatment for the primary hematologic diseases [6][7][8] . Indeed, the most prevalent causative microorganisms were Gram-negative species, such as Pseudomonas aeruginosa or Escherichia coli, from the 1970's to the late 1980's. ...
In order to improve the management of infectious complications associated with hematologic disorders, we conducted a retrospective 5-year analysis of Blood Culture (BC) tests obtained from febrile patients with hematological disorders treated in our institute between 2010 and 2014. BCs were performed using the BacT/ALERT 3D system (bioMérieux, Marcy l'Etoile, France) and identification and antibiotic susceptibility testing were performed using VITEK2 (bioMérieux). In 8,549 BC tests obtained from 1,517 febrile events, 325 BC tests showed positive results in 154 febrile episodes with 91 patients. In BC-positive episodes, the incidence of BC-positivity for 3 consecutive BC tests per febrile episode was 98.1 %. The frequencies of Gram-positive and Gram-negative bacteria as the causative pathogen were almost equal (44.5 % vs 43.3 %). The frequency of drug-resistant bacteria, such as either methicillin-resistant cocci or extended spectrum beta-lactamase producing organism, was more than 50 %. The use of a central venous catheter showed a positive relationship with the methicillin-resistant cocci in our series. Our study found increasing frequencies of drug-resistant bacteria as the pathogens of blood stream infection in hematological disorders. These results are instructive for the appropriate selection of empiric antibiotic therapy for febrile events in patients with hematologic malignancies.
Central venous catheters (CVCs) are important for maintenance of childhood leukemia treatment but CVCs may develop complications. The aim of this study was to retrospectively evaluate the CVC-related complication rate, complication types, and outcome in children with acute leukemia. Complications developing in 310 CVCs (ports n=250, Hickman catheters n=60) inserted in 262 patients were evaluated. A total of 225,296 catheter days were screened. Median (range) CVC in-dwelling time was 661.5 (1 to 2636) days. In total, 157 complications developed of which 91 (58%) were infectious complications, 35 (22.3%) were vascular, 19 (12.1%) were surgical, and 12 (7.6%) were mechanical. Hickman catheters had a higher complication rate and were more prone to mechanical complications (P<0.01) but there was no difference for other complications. A lower absolute neutrophil count at insertion was observed in children with infectious complications (P<0.01). Seventy-eight of 136 catheters (57.3%) had to be removed prematurely. The overall complication rate was 0.65 per 1000 catheter days. In multivariate analysis, relapse leukemia, Hickman catheter and low absolute neutrophil count increased complication risk by 4.00, 1.97, and 1.92 times, respectively. Five (1.9%) deaths occurred because of catheter complications. Safe use of CVCs can be improved by early detection of complications and an experienced catheter care team.
Rationale
To understand the risk factors for catheter-related infection during treatment of pediatric cancer is essential to implement measures to prevent its occurrence.
Objective
We performed a comprehensive systematic review of the literature with meta-analysis to identify and synthesize the main risk factors for catheter-related infection in children undergoing oncological treatment.
Methods
Systematic searches were conducted in Medline, Embase, Lilacs, and BVS (Biblioteca Virtual em Saúde) until January 2022, following PRISMA guidelines. The search was not limited to language or dates. Risk factors were divided into host-related, assistance-related, and catheter types. We also describe the most common pathogens.
Results
Thirteen studies were included in the review. Diagnosis of hematological neoplasm, the intensity of treatment, blood transfusion in the 4-7 days before the infection, type of long-term catheters (tunneled externalized catheters, double lumen, greater diameter), inpatient treatment, and a longer period of hospitalization were the most consistent risk factors. Metanalysis showed that neutropenia at the moment of catheter placement is not a risk factor for central-line-associated bloodstream infections, however, there is high heterogeneity between studies. Staphylococcus epidermidis was the most common pathogen reported.
Conclusions
Understanding risk factors is an essential step to reduce morbidity and mortality of catheter-related infection. Education for preventive measures, reduction of hospitalization, wisely choosing the most adequate type of catheter, and the best moment for catheter insertion may reduce the occurrence of catheter-related infection.
Background:
Children with acute lymphoblastic leukemia (ALL) require central lines to facilitate their care. Peripherally inserted central catheters (PICCs) may have lower rates of central line-associated bloodstream infections (CLABSIs) versus other central lines.
Objectives:
The objective of this study was to compare the CLABSI rate in the first month of therapy after initiating a policy to place PICCs in new patients with severe neutropenia (SN) and Mediports in those with moderate-to-no neutropenia. We also examined thrombosis rates.
Design/method:
We prospectively gathered data on new patients for 2.5 years following the policy change and retrospectively for the 2 years prior and compared rates of CLABSIs and thrombosis.
Results:
CLABSIs decreased in SN patients from 7.52/1000 to 3.11/1000 line days (P=0.33). The CLABSI rate for all patients with SN who had a Mediport was 13.39/1000 versus 4.08/1000 line days for those that received PICCs (P=0.15). The thrombosis rate for Mediport patients was 3.13 clots/1000 versus 7.65/1000 line days for PICC patients, but the difference was not significant (P= 0.11).
Conclusion:
The differences observed suggest that placing PICCs versus Mediports in new ALL patients with SN may result in a lower incidence of CLABSIs in the first month of therapy without a significant increase in thrombosis.
The differences in overall morbidity by induction treatment regimen for pediatric acute lymphoblastic leukemia (ALL) are unknown. We examined a cohort of children with ALL who received induction chemotherapy between January 2010 and May 2018. We evaluated 20 clinically relevant adverse events (AEs) and readmission and ICU admission rates. Outcomes were compared between standard 3- and 4-drug treatment regimens in multivariate analyses using Cox proportional hazard ratios. Among 486 eligible patients, the risks of sepsis (HR = 2.16, 95% CI = 1.11–4.19), hypoxia (HR = 2.08, 95% CI = 1.03–4.18), hyperbilirubinemia (HR = 2.48, 95% CI = 1.07–5.74), hyperglycemia (HR = 2.65, 95% CI = 1.29–5.42), thromboembolic event (HR = 4.50, 95% CI = 1.30–15.6), and hyponatremia (HR = 7.88, 95% CI = 1.26–49.4) were significantly higher during 4-drug induction. Despite no differences in readmission or ICU admission rates, 4-drug induction patients had greater total inpatient days (12 vs. 4 days; p<.0001). In conclusion, pediatric patients receiving 4-drug induction for ALL experience higher morbidity. These results inform care practices and patient guidance during induction therapy.
Purpose
The purpose of this study is to identify controllable treatment-environment-related factors affecting the timing of a central line-associated bloodstream infection (CLABSI) onset in children with cancer with central venous catheters (CVC).
Design
This study is a secondary data analysis with the data extracted from electronic medical records in a tertiary hospital in South Korea. This study was conducted by reviewing electronic medical records of 470 pediatric cancer patients younger than the age of 18 years from 2010 to 2016.
Method
The timing of a CLABSI onset was identified through the onset of CLABSI and the duration of catheterization. Cox proportional hazards regression analysis was used to estimate the impact of variables on the timing of CLABSI onset. The duration of catheterization was estimated using the Kaplan–Meier method.
Finding
Multivariable analysis by Cox proportional model analysis showed that there are six independent variables affecting the timing of a CLABSI onset: length of stay in hospital, catheter insertion location, use of antibiotics on day of catheter insertion, catheter function, number of blood transfusions per 100 days, and number of blood tests per 100 days.
Conclusions
The findings of this study provide a foundation for the development of EBP-based CVC guidelines to effectively reduce CLABSIs and maintain a long-term CVC without a CLABSI.
Acute lymphoblastic leukemia shows marked differences in outcome between children and adults. Since there is limited information on the distribution of clinico-biologic variables in different age cohorts, we analyzed 5202 ALL patients enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in 9 age cohorts. The highest prevalence of ALL was observed in children, although a second peak was recorded from the 4th decade onwards. Interestingly, the lowest incidence was found in females between 14-40 years, suggesting a protective impact of fertility. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated to MLL/AF4 positivity, was more frequent in patients between 10-50 years. A T-lineage (14.2%) was rare among small children and increased in 10-40 years patients. The BCR/ABL1 rearrangement increased progressively with age, starting from the 10-14 cohort and impacting for 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5th decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that adolescents and young adults are characterized by a male prevalence, greater T-lineage acute lymphoblastic leuekmia percentage, an increase of poor prognostic molecular markers with aging compared to children, and conclusively quantifies the progressive increase with age of BCR/ABL+ patients, potentially manageable by targeted therapies.
Background
When an infection is suspected in a child with cancer and a central venous line (CVL), cultures are often only obtained from the CVL and not from a peripheral vein (PV). This study was undertaken to evaluate the importance of concomitant blood cultures from the CVL and a PV.ProcedureClinical data and the results of all cultures taken concomitantly from the CVL and a PV were registered prospectively in children admitted with fever from April 2008 to December 2012 at the Department of Pediatrics at Aarhus University Hospital Skejby.ResultsDuring the study period 654 paired cultures obtained from the CVL and from a PV within two hour of each other were included. A true bloodstream infection (BSI) was registered in 112 episodes. In 20 (17%) out of 112, true BSI growth of a microorganism was detected only in the culture from a PV including seven cases of Escherichia coli and three cases of Staphylococcus aureus. In 52 episodes the same microorganism was cultured from both the CVL and a PV. Twenty-four of these episodes were classified as catheter-related bloodstream infections (CRBSI) using differential time to positivity. In total, 64 (57%) of all true BSI were defined as CRBSI.Conclusions
Blood cultures should be obtained from a PV in addition to cultures from CVL at the onset of fever in pediatric patients with cancer in order to maximize the findings of true BSIs. The frequency of CRBSI may be over-estimated if blood cultures are drawn from CVL only. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
In this article, the American Cancer Society provides estimates of the number of new cancer cases and deaths for children and adolescents in the United States and summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries (which are reported in detail for the first time here and include high-quality data from 45 states and the District of Columbia, covering 90% of the US population). In 2014, an estimated 15,780 new cases of cancer will be diagnosed and 1960 deaths from cancer will occur among children and adolescents aged birth to 19 years. The annual incidence rate of cancer in children and adolescents is 186.6 per 1 million children aged birth to 19 years. Approximately 1 in 285 children will be diagnosed with cancer before age 20 years, and approximately 1 in 530 young adults between the ages of 20 and 39 years is a childhood cancer survivor. It is therefore likely that most pediatric and primary care practices will be involved in the diagnosis, treatment, and follow-up of young patients and survivors. In addition to cancer statistics, this article will provide an overview of risk factors, symptoms, treatment, and long-term and late effects for common pediatric cancers. CA Cancer J Clin 2014. (©) 2014 American Cancer Society.
Background:
The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.
Design and methods:
We analyzed 749 patients aged 1-45 yr treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard-, intermediate-, or high-risk treatment with or without hematopoietic stem cell transplantation.
Results:
Adults aged 18-45 had significantly lower WBCs at diagnosis compared with children aged 1-9 and 10-17 yr, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; P < 0.0001) or high-risk chemotherapy with transplantation (4%, 13%, 19%; P < 0.0001). This age-dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, P < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; P < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; P = 0.005) in older patients.
Conclusions:
Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high-risk therapy, which should be considered when comparing pediatric and adult outcomes.
We draw upon a series of articles in which a method based on pseu- dovalues is proposed for direct regression modeling of the survival function, the restricted mean, and the cumulative incidence function in competing risks with right-censored data. The models, once the pseudovalues have been computed, can be fit using standard generalized estimating equation software. Here we present Stata procedures for computing these pseudo-observations. An example from a bone marrow transplantation study is used to illustrate the method.
Central venous catheters (CVCs) are essential in the management of pediatric patients receiving antineoplastic therapy or bone marrow transplants, and have significantly improved their quality of life, but CVC-related infectious complications are a major source of morbidity. It has been estimated that 14-51 % of the CVCs implanted in children with malignancies may be complicated by bacteremia, and that the incidence of infections is 1.4-1.9 episodes per 1,000 CVC days. However, there are few recent data concerning the epidemiology of CVC-related infections, the prevalence of antimicrobial resistance in their etiology, or the main factors associated with an increased risk of infection by type of catheter, patient age, the type of cancer, or the presence of neutropenia. Moreover, although various new strategies have been proposed in an attempt to reduce the risk of CVC-related infections, such as catheters impregnated with antiseptics/antibiotics, lock antibiotic prophylaxis, the use of ointments at the exit site, and antithrombotic prophylaxis, their real efficacy in children has not yet been demonstrated. The management of CVC-related infections remains difficult, mainly because of the number of still open questions (including the choice of optimal antimicrobial therapy because of the increasing isolation of multiresistant bacterial strains, treatment duration, whether catheters should be removed or not, the feasibility of guidewire exchange, and the usefulness of antibiotic lock therapy) and the lack of studies of children with cancer. Only well-designed, prospective clinical trials involving pediatric cancer patients can clarify optimal prevention and treatment strategies for CVC-related infections in this population.
Tunneled central venous catheters (CVCs) are inevitable in children with acute lymphoid leukemia (ALL). The aim of this study was to evaluate the risk of CVC-related complications in children with ALL in relation to timing of catheter placement and type of catheter.
All children hospitalized from January 2000 to March 2008 with newly diagnosed ALL and with double-lumen total implantable devices (TIDs) or tunneled external catheters (TEs) were included retrospectively. We only used data related to the patient's first catheter.
We included 98 children; 35 received a TID and the remaining 63 received a TE. A total number of 29,566 catheter days and 93 catheter-associated blood stream infections (CABSI) was identified. We found a CABSI rate of 3.1/1,000 catheter days (5.4/1,000 catheter days for TEs and 1.4/1,000 catheter days for TIDs, incidence rate ratio (IRR) 3.82 (95% CI 2.37-6.35) P = 0.0001). No difference was found in CABSI between neither early versus later placed TIDs (IRR = 0.99 (95% CI 0.41-2.45) P = 0.98) nor early versus later placed TEs (IRR = 0.81 (95% CI 0.40-1.86) P = 0.54). We found no difference between early and later placed catheters regarding non-elective removal (RR = 0.86 (95% CI 0.72-1.03) P = 0.09). TEs had a higher risk of non-elective removal compared with TIDs (RR = 3.95 (95% CI 1.88-8.29) P < 0.001).
The study did not find that children with ALL and with early placed CVCs experienced significantly more complications compared with children with late placed catheters. This study found that children with ALL and TEs experienced more complications than children with TIDs.
The primary objective was to describe microbiologically documented infections during induction therapy for acute lymphoblastic leukemia. The secondary objectives were to describe risk factors for microbiologically documented infections and for patients with a febrile episode, to identify risk factors for recurrence of fever or reinitiation of antibiotics.
This study was a retrospective review of children from 1 to 18 years of age who received induction chemotherapy between March 1997 and September 2006. Microbiologically documented infections were examined through the induction period.
There were 425 children evaluated. The most common pre-existing risk factor for infection was Down syndrome in 11 children. Of the 425 children, 83 (19.5%) experienced at least one microbiologically documented infection. There were 85 infections consisting of 65 bacterial, 15 viral and 5 fungal infections.Variables significantly associated with a microbiologically documented infection were pre-existing risk factors (odds ratio [OR]: 3.63; P = 0.01) and neutropenia at initial infectious episode (OR: 1.86; P = 0.03). Factors associated with recurrence of fever and reinitiation of antibiotics after an initial infectious episode were receipt of a 4-drug induction, neutropenia at the initial infectious episode, initial fever documented in hospital, and lack of bone marrow recovery at the time of initial antibiotic cessation.
About 20% of children with acute lymphoblastic leukemia have a microbiologically documented infection during induction. Those with pre-existing risk factors and neutropenia at the initial infectious episode were at higher risk of microbiologically documented infection. Continued efforts to refine risk groups may allow for risk-directed prophylactic or empiric strategies.
Although venipuncture is the preferred method for obtaining blood cultures, specimens often are obtained from intravenous
catheters (IVC). For IVC-drawn blood cultures, some authorities recommend discarding the initial 5 to 10 ml of blood to reduce
contamination and remove potential inhibitory substances. To determine whether this practice reduced contamination rates (CR),
we assessed the results of IVC-drawn blood cultures for adults. Thirty milliliters of blood was obtained aseptically. The
first 10 ml, rather than being discarded, was inoculated into an aerobic culture vial. Using a second sterile syringe, 20
ml of blood was obtained and inoculated in 10-ml aliquots to aerobic and anaerobic culture vials. Positive cultures were evaluated
to assess clinical significance (true versus contaminant). Out of 653 IVC-drawn blood culture pairs, both vials were contaminated
in 38 pairs (5.8%); only the “discard” vial was contaminated in 33 (5.1%); and only the “standard” vial was contaminated in
31 (4.7%). Overall CR were 10.9% for the discard vial versus 10.5% for the standard vial (P = 0.90). We conclude that discarding an initial aliquot of blood when obtaining blood cultures from IVCs does not reduce
CR.
To evaluate the effectiveness of methods that control for confounding by indication, we compared breast cancer recurrence rates among women receiving adjuvant chemotherapy with those who did not.
In a medical record review-based study of breast cancer treatment in older women (n=1798) diagnosed between 1990 and 1994, our crude analysis suggested that adjuvant chemotherapy was positively associated with recurrence (hazard ratio [HR]=2.6; 95% confidence interval [CI]=1.9, 3.5). We expected a protective effect, so postulated that the crude association was confounded by indications for chemotherapy. We attempted to adjust for this confounding by restriction, multivariable regression, propensity scores (PSs), and instrumental variable (IV) methods.
After restricting to women at high risk for recurrence (n=946), chemotherapy was not associated with recurrence (HR=1.1; 95% CI=0.7, 1.6) using multivariable regression. PS adjustment yielded similar results (HR=1.3; 95% CI=0.8, 2.0). The IV-like method yielded a protective estimate (HR=0.9; 95% CI=0.2, 4.3); however, imbalances of measured factors across levels of the IV suggested residual confounding.
Conventional methods do not control for unmeasured factors, which often remain important when addressing confounding by indication. PS and IV analysis methods can be useful under specific situations, but neither method adequately controlled confounding by indication in this study.
To describe patterns of central venous catheter (CVC) use and determine the risk of infection associated with a catheter in children with acute lymphoblastic leukemia (ALL).
Children with ALL (n = 1934), participating in Children's Cancer Group studies for good-prognosis ALL (CCG-1881) and intermediate-risk ALL (CCG-1891) were evaluated in a retrospective case-control study. The presence of a catheter and the occurrence of infectious complications were recorded after each treatment phase.
Young age and enrollment in the intermediate-risk study were associated with higher rates of catheter use. During each of the first four phases of therapy, the adjusted risk of infection was two- to fourfold higher when a catheter was in place. The proportion of patients with infection during the first four phases of therapy was 2.6 times higher with a CVC (14.4% versus 5.7%). Catheter use was associated with significantly increased hospitalization rates during induction, consolidation, and interim maintenance, but not during delayed intensification. A catheter did not significantly increase the risk of fever during neutropenia.
The presence of a CVC increases the risk of infection during the early phases of low-intensity therapy for ALL.
Despite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2-5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology-ALL92 protocol included 1652 patients < or =15 years of age with precursor B- and T-cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment-related death (TRD) [relative risk (RR) = 2.2; 95% confidence interval (CI(95%)): 1.2-4.0, P < 0.01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4.5; CI(95%): 2.0-10.2, P < 0.00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL.
To better understand the absolute and relative risks of bloodstream Infection (BSI) associated with the various types of intravascular devices (IVDs), we analyzed 200 published studies of adults In which every device in the study population was prospectively evaluated for evidence of associated infection and microbiologically based criteria were used to define IVD-related BSI.
English-language reports of prospective studies of adults published between January 1, 1966, and July 1, 2005, were identified by MEDLINE search using the following general search strategy: bacteremla [Medical Subject Heading, MeSH] OR septicemia [MeSH] OR bloodstream Infection AND the specific type of intravascular device (e.g., central venous port). Mean rates of IVD-related BSI were calculated from pooled data for each type of device and expressed as BSIs per 100 IVDs (%) and per 1000 IVD days.
Point incidence rates of IVD-related BSI were lowest with peripheral Intravenous catheters (0.1%, 0.5 per 1000 IVD-days) and midline catheters (0.4%, 0.2 per 1000 catheter-days). Far higher rates were seen with short-term noncuffed and nonmedicated central venous catheters (CVCs) (4.4%, 2.7 per 1000 catheter-days). Arterial catheters used for hemodynamic monitoring (0.8%, 1.7 per 1000 catheter-days) and peripherally inserted central catheters used in hospitalized patients (2.4%, 2.1 per 1000 catheter-days) posed risks approaching those seen with short-term conventional CVCs used in the Intensive care unit. Surgically implanted long-term central venous devices--cuffed and tunneled catheters (22.5%, 1.6 per 1000 IVD-days) and central venous ports (3.6%, 0.1 per 1000 IVD-days)--appear to have high rates of Infection when risk Is expressed as BSIs per 100 IVDs but actually pose much lower risk when rates are expressed per 1000 IVD-days. The use of cuffed and tunneled dual lumen CVCs rather than noncuffed, nontunneled catheters for temporary hemodlalysis and novel preventive technologies, such as CVCs with anti-infective surfaces, was associated with considerably lower rates of catheter-related BSI.
Expressing risk of IVD-related BSI per 1000 IVD-days rather than BSIs per 100 IVDs allows for more meaningful estimates of risk. These data, based on prospective studies In which every IVD in the study cohort was analyzed for evidence of infection by microbiologically based criteria, show that all types of IVDs pose a risk of IVD-related BSI and can be used for benchmarking rates of infection caused by the various types of IVDs In use at the present time. Since almost all the national effort and progress to date to reduce the risk of IVD-related Infection have focused on short-term noncuffed CVCs used in Intensive care units, Infection control programs must now strive to consistently apply essential control measures and preventive technologies with all types of IVDs.
Indwelling vascular catheters are a leading source of bloodstream infections in critically ill patients and cancer patients. Because clinical diagnostic criteria are either insensitive or non-specific, such infections are often overdiagnosed, resulting in unnecessary and wasteful removal of the catheter. Catheter-sparing diagnostic methods, such as differential quantitative blood cultures and time to positivity have emerged as reliable diagnostic techniques. Novel preventive strategies include cutaneous antisepsis, maximum sterile barrier, use of antimicrobial catheters, and antimicrobial catheter lock solution. Management of catheter-related bloodstream infections involves deciding on catheter removal, antimicrobial catheter lock solution, and the type and duration of systemic antimicrobial therapy. Such decisions depend on the identity of the organism causing the bloodstream infection, the clinical and radiographical manifestations suggesting a complicated course, the underlying condition of the host (neutropenia, thrombocytopenia), and the availability of other vascular access sites.
Catheter-associated blood stream infections (CABSI) are frequent complications encountered with cancer treatment. In order to understand which factors might predispose to CABSIs in children and young adults, we evaluated risk for infection in association with tumor type, catheter type, and setting of occurrence.
All pediatric oncology patients having a central venous catheter (CVC) with a tunneled external (TE) or totally implantable design (TID) were prospectively followed for the occurrence of a CABSI for 12 months. CABSIs were defined in accordance with the guidelines published by the Centers for Disease Control, and were quantified as the number of occurrences per 1,000 device days. Rates of CABSIs were stratified by tumor histology, type of catheter design, and setting of occurrence. Statistical comparisons were made using the Mantel-Haenzel statistic and the Cox proportional hazard model.
A total of 58 CABSIs were identified in 139 patients over a period of 35,935 CVC days. The overall CABSI rate was 1.6 infections per 1,000 CVC days (95% CI 1.2, 2.1). Stratified analysis demonstrated increased risk for CABSIs in hospitalized patients having TEs, and while patients with solid tumors were also at higher risk; this association was not supported by the Cox proportional hazard model.
While our baseline CABSI rate was comparatively lower than for other institutions, subset analyses identified that hospitalized cancer patients having TEs are at the highest risk for developing CABSIs. Our findings may help to guide improved methods of anticipating and controlling infections in immunocompromised patients.
. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia.
- Schmiegelow