Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates.

2012

1252-7

2012 Dec

1532-0987

<p><strong>BACKGROUND: </strong>Candida species are the third most common cause of pediatric health care-associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis.</p>

<p><strong>METHODS: </strong>From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis.</p>

<p><strong>RESULTS: </strong>Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes.</p>

<p><strong>CONCLUSIONS: </strong>We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.</p>

10.1097/INF.0b013e3182737427

Pediatr. Infect. Dis. J.

22982980

Potential for pet animals to harbour methicillin-resistant Staphylococcus aureus when residing with human MRSA patients.

2012

286-93

2012 Jun

1863-2378

<p>Colonization by methicillin-resistant Staphylococcus aureus (MRSA) may be persistent in people and is horizontally transmissible. The scientific literature suggests that domestic pets may also participate in cross-transmission of MRSA within households. The objectives of this study were to evaluate the prevalence of and risk factors for MRSA carriage by pets residing in households with an MRSA-infected person. From 66 households in which an MRSA-infected patient resided, we screened 47 dogs and 52 cats using a swab protocol. Isolates from pets and humans were genotyped using two techniques and compared for concordance. Human participants completed a 22-question survey of demographic and epidemiologic data relevant to staphylococcal transmission. Eleven of 99 pets (11.5%) representing 9 (13.6%) of households were MRSA-positive, but in only six of these households were the human and animal-source strains genetically concordant. Human infection by strain USA 100 was significantly associated with pet carriage [OR = 11.4 (95% CI 1.7, 76.9); P = 0.013]. Yet, for each day of delay in sampling the pet after the person's MRSA diagnosis, the odds of isolating any type of MRSA from the pet decreased by 13.9% [(95% CI 2.6, 23.8); P = 0.017)]. It may be concluded that pets can harbour pandemic strains of MRSA while residing in a household with an infected person. However, the source of MRSA to the pet cannot always be attributed to the human patient. Moreover, the rapid attrition of the odds of obtaining a positive culture from pets over time suggests that MRSA carriage may be fleeting.</p>

10.1111/j.1863-2378.2011.01448.x

Zoonoses Public Health

22233337

A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies.

2014

O50-7

2014 Jan

1469-0691

<p>Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p &lt;0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p &lt;0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.</p>

10.1111/1469-0691.12312

Clin. Microbiol. Infect.

23889746

Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia.

2013

1633-9

2013 Aug

1029-2403

<p>Antibiotic variation among pediatric oncology patients has not been well-described. Identification of significant variability in antibiotic use within this population would warrant evaluation of its clinical impact. We conducted a retrospective cohort study of newly diagnosed patients with pediatric acute lymophoblastic leukemia (ALL) hospitalized from 1999 to 2009 in 39 freestanding US children's hospitals within the Pediatric Health Information System. Medication use data were obtained for the first 30 days from each patient's index ALL admission date. Antibiotic exposure rates were reported as antibiotic days/1000 hospital days. Unadjusted composite broad-spectrum antibiotic exposure rates varied from 577 to 1628 antibiotic days/1000 hospital days. This wide range of antibiotic exposure was unaffected by adjustment for age, gender, race and days of severe illness (adjusted range: 532-1635 days of antibiotic therapy/1000 hospital days). Antibiotic use for children with newly diagnosed ALL varies widely across children's hospitals and is not explained by demographics or illness severity.</p>

10.3109/10428194.2012.750722

Leuk. Lymphoma

23163631

Use of administrative data for the identification of laboratory-confirmed influenza infection: the validity of influenza-specific ICD-9 codes

2012

63-66

February 2012

Antifungal prophylaxis associated with decreased induction mortality rates and resources utilized in children with new-onset acute myeloid leukemia.

2014

502-8

02/2014

1537-6591

<p><strong>BACKGROUND: </strong>Invasive fungal infections cause significant morbidity and mortality for children with acute myeloid leukemia (AML). Data on the comparative effectiveness of antifungal prophylaxis in this population are limited.</p>

<p><strong>METHODS: </strong>A pediatric AML cohort was assembled from the Pediatric Health Information System database using ICD-9 codes and pharmacy data. Antifungal prophylaxis status was determined by pharmaceutical data review within 21 days of starting induction chemotherapy. Patients were followed until end of induction, death, or loss to follow-up. Cox regression analyses compared induction mortality and resources utilized between patients receiving and not receiving antifungal prophylaxis. A propensity score accounted for variation in demographic factors, location of care, and severity of illness at presentation.</p>

<p><strong>RESULTS: </strong>Eight hundred seventy-one AML patients were identified; the induction case fatality rate was 3.7%. In the adjusted Cox regression model, patients receiving antifungal prophylaxis (57%) had a decreased hazard for induction mortality (hazard ratio [HR], 0.42; 95% confidence interval [CI], .19-.90). Children receiving prophylaxis were less frequently exposed to broad-spectrum gram-positive (incidence rate ratio [IRR], 0.87; 95% CI, .79-.97) and antipseudomonal β-lactam agents (HR, 0.91; 95% CI, .85-.96), had fewer blood cultures (IRR, 0.78; 95% CI, .71-.86), and had fewer chest CT scans (IRR, 0.73; 95% CI, .60-.88).</p>

<p><strong>CONCLUSIONS: </strong>Antifungal prophylaxis in pediatric AML patients was associated with reduced induction mortality rates and supportive care resources. Further investigation is necessary to determine whether antifungal prophylaxis should include antimold activity.</p>

10.1093/cid/cit781

Clin. Infect. Dis.

24270167

Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States.

2014

112-20

02/2014

1529-7535

<p><strong>OBJECTIVE: </strong>Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality.</p>

<p><strong>SETTING: </strong>Forty-three children's hospitals contributing data to the Pediatric Health Information System database.</p>

<p><strong>PATIENTS: </strong>Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64-3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89-1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999-2003 vs 16.4% in 2004-2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999-2003 vs 6.5% in 2004-2010 in the nononcology cohort, p &lt; 0.0001).</p>

<p><strong>CONCLUSIONS: </strong>Pediatric patients with acute myeloid leukemia frequently required intensive care resources, with mortality rates substantially lower than previously reported. Mortality also decreased over the time studied. Pediatric acute myeloid leukemia patients with sepsis who required intensive care had a mortality comparable to children without oncologic diagnoses; however, overall mortality and mortality for each category of organ failure studied was higher for the acute myeloid leukemia cohort compared with the nononcology cohort.</p>

10.1097/PCC.0000000000000042

Pediatr Crit Care Med

24366507

Risk factors for renal failure in pediatric patients with acute myeloid leukemia: a retrospective cohort study.

2010

655-61

2010 Oct

1545-5017

<p><strong>BACKGROUND: </strong>In children receiving treatment for acute myeloid leukemia (AML) there is often concern for the development of acute renal failure (ARF). Despite this, data are limited to define the incidence of ARF in this population. This study aims to evaluate the rate of ARF in AML patients and to delineate the impact of age, race, various co-morbid conditions and antimicrobial agents on the development of ARF.</p>

<p><strong>METHODS: </strong>A cohort of newly diagnosed AML patients from children's hospitals across the United States was identified using the Pediatric Health Information Systems database. Information regarding demographics, discharge diagnoses, pharmaceutical exposures, and hospital resource utilization were collected for each hospitalization for up to 1 year from AML diagnosis. Cox regression analysis was used to define the hazard ratios for development of ARF by demographic variables, co-morbid conditions, and exposure to various antimicrobial agents.</p>

<p><strong>RESULTS: </strong>Within 1 year of AML diagnosis, 135 (16.2%) patients were diagnosed with ARF. After adjustment for the presence of co-morbid conditions, the risk for ARF was greater in older patients and in black patients. Vancomycin exposure duration of greater than 48 hr and carbapenem exposure duration greater than 10 days were associated with an increased risk for ARF.</p>

<p><strong>CONCLUSION: </strong>ARF is a relatively common problem in children with AML. Future studies should address the different risks of ARF by age and race. Empiric therapy with potentially nephrotoxic agents did not increase the risk of nephrotoxicity. Patients on prolonged vancomycin therapy should be monitored closely for development of ARF.</p>

10.1002/pbc.22601

Pediatr Blood Cancer

20533519

Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza.

2009

447-9

2009 Mar

1097-6833

<p>Many children with influenza are treated with antibiotics. In this report, we describe the rate and indications for antibacterial use in children hospitalized with influenza. A total of 333 of 729 (46%) patients received &gt;2 days of treatment with antibacterial medications, of whom 36% did not have an apparent indication for therapy.</p>

10.1016/j.jpeds.2008.09.026

J. Pediatr.

19874761

Treatment with oseltamivir in children hospitalized with community-acquired, laboratory-confirmed influenza: review of five seasons and evaluation of an electronic reminder.

2009

171-8

2009 Mar

1553-5606

<p><strong>BACKGROUND: </strong>When initiated within 48 hours of the onset of symptoms, oseltamivir has been shown to reduce severity and length of influenza illness. Few studies have evaluated the use of oseltamivir in patients hospitalized with influenza.</p>

<p><strong>OBJECTIVE: </strong>To describe the prescribing practices for oseltamivir in children hospitalized with influenza and to evaluate a mechanism to improve the rate of appropriate prescription.</p>

<p><strong>DESIGN, SETTING, PATIENTS: </strong>Retrospective cohort study of 929 patients aged 21 years or younger hospitalized with community-acquired laboratory-confirmed influenza (CA-LCI) during 5 consecutive seasons (2000-2005). We examined oseltamivir eligibility, which included patients 1 year of age or older with an influenza test result available within 48 hours of symptom onset. During the 2005-2006 season, an observational trial of an electronic reminder was conducted to improve the frequency of oseltamivir prescription.</p>

<p><strong>MEASUREMENTS: </strong>Oseltamivir prescription.</p>

<p><strong>RESULTS: </strong>Of 305 patients (32.8%) eligible for treatment with oseltamivir, 49 (16.1% of those eligible) were prescribed oseltamivir during hospitalization. Prescription rates for indications consistent with the US Food and Drug Administration (FDA) approval ("on label") increased from 0% to 37.2% over 5 seasons (P &lt; 0.0001). Prescriptions outside this recommendation ("off label") also increased over 5 seasons (P &lt; 0.0001). Twenty-nine (5%) of 624 patients were treated with oseltamivir off label; 11 were less than 1 year of age. Initiation of a reminder had no impact on prescription (P &gt; 0.05).</p>

<p><strong>CONCLUSIONS: </strong>Oseltamivir was used infrequently for children hospitalized with influenza. In addition, use inconsistent with the FDA label of oseltamivir occurs. Mechanisms are needed to improve appropriate prescription of oseltamivir.</p>

10.1002/jhm.431

J Hosp Med

19301375