medRxiv (Cold Spring Harbor Laboratory), Mar 18, 2022
The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options f... more The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.
INTRODUCTION Ultrasound (US) imaging is preferred in the initial evaluation for children with sus... more INTRODUCTION Ultrasound (US) imaging is preferred in the initial evaluation for children with suspected nephrolithiasis; however, computed tomography (CT) continues to be used in this setting with resultant unnecessary ionizing radiation exposure. The study institution implemented a standardized clinical pathway to reduce rates of CT utilization for children with nephrolithiasis. OBJECTIVE The aim of this study was to evaluate the impact of this pathway on initial imaging strategies for children with suspected nephrolithiasis. STUDY DESIGN A standardized pathway was designed and implemented using a systematic quality improvement process. A suspected cohort was created using 'reason for study' search terms consistent with a nephrolithiasis diagnosis. A confirmed cohort of children with a final diagnosis of nephrolithiasis was derived from this suspected cohort. The primary outcome was CT use as the initial imaging study in children with suspected or confirmed nephrolithiasis presenting to the emergency department (ED) between October 2013 and February 2018. Comparisons were made before and after pathway implementation (October 2015). Secondary outcomes included rates of CT scan within 30 days, while balancing measures included rates of admission, ED length of stay, and return visits. RESULTS A total of 534 children with suspected (220 prepathway; 314 postpathway) and 90 children with confirmed (37 prepathway; 53 postpathway) nephrolithiasis were included. For the suspected cohort, CT scans performed as the initial imaging evaluation (9.2% vs 2.5%, P = 0.001) and at any time during the index visit (15.7% vs 5.7%, P = 0.001) decreased after pathway implementation. Within the confirmed cohort, a non-significant decrease in initial CT rates was observed after implementation. No differences were observed in admission rates or ED length of stay after implementation. A trend toward lower return visits to the ED was seen after pathway implementation (5.5% vs 2.2%, P = 0.058). DISCUSSION Within a tertiary care pediatric ED associated with a strong institutional experience with clinical pathways, initial CT rates were decreased after pathway implementation for children with suspected nephrolithiasis. While retrospective assessment of suspected disease is limited, this is one of the first studies to address imaging patterns for nephrolithiasis beyond the final discharge diagnosis, thus capturing a broader cohort of children. Children with suspected nephrolithiasis can be safely managed with an US-first approach, and postvisit CT scans are rarely necessary for management. CONCLUSIONS A standardized clinical pathway for suspected nephrolithiasis can reduce rates of initial and overall CT utilization without adversely impacting downstream care.
Background: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with ... more Background: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for highrisk infants with CMV infection. Methods: We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). Results: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. Conclusions: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.
Background. Infectious complications of chimeric antigen receptor (CAR) T-cell immunotherapy in c... more Background. Infectious complications of chimeric antigen receptor (CAR) T-cell immunotherapy in children and young adults have not been well described. Methods. Medical records of patients ≤26 years old receiving CD19 CAR T-cell infusion (CTI) at a single institution between 2014 and 2017 were reviewed. The number of infections per 100 days-at-risk (infection density) in the 90 days preceding and 0-28 and 29-90 days after CTI was calculated. Poisson regression and Cox analyses were utilized to identify risk factors for infections. Results. Eighty-three patients received CTI during the study period. Most patients (98%) had refractory or relapsed acute lymphoblastic leukemia (ALL). Infections occurred in 54% of patients in the 90 days before CTI (infection density, 1.23) and in 40% of patients in the first 28 days following CTI (infection density, 2.89). Infection density decreased to 0.55 in the 29-90 days post-CTI. Most infections were bacteremias (39%) or respiratory viral infections (43%). Pre-CTI risk factors associated with infection included prior hematopoietic cell transplantation (HCT), immunoglobulin G (IgG) level <400 mg/dL, and lymphodepletion other than cyclophosphamide plus fludarabine; post-CTI risk factors included higher-severity CRS and IgG <400 mg/dL. Conclusions. Infection rates in children and young adults receiving CD19 CAR T-cell therapy increase in the first month and then decline. Understanding types and timing of infections and contributing risk factors may help inform prophylactic and monitoring strategies. Specific attention should be given to patients with prior HCT, severe hypogammaglobulinemia, and severe CRS.
Purpose/Objectives: In August 2013, our institution implemented a standardized pathway for skin a... more Purpose/Objectives: In August 2013, our institution implemented a standardized pathway for skin and soft tissue infections (SSTI), based on national guidelines and local consensus. The pathway aimed to improve antimicrobial stewardship. We evaluated the impact of this pathway on antibiotic prescribing patterns for infections seen …
Censoring occurred at the time of death, loss to follow-up or 10 years. Univariable and multivari... more Censoring occurred at the time of death, loss to follow-up or 10 years. Univariable and multivariable hazard ratios (HR) were calculated using a Cox model, treating relapse and rejection following CMV as time-varying covariates. Results. Seventy-nine kidney, 52 heart, 34 liver and five liver-kidney transplant recipients were included. Sixty-two of 170 died, at a median of 3.8 years (interquartile range [IQR] 0.8-6.6 years). Median follow-up amongst the 108 survivors was 7.4 years (IQR 3.7-10 years) although 22 (13%) were censored before 3 years. CMV relapse occurred in 49/170 (29%), 67% within 6 months of treatment completion. Overall mortality amongst those who relapsed was 39% (19/49) vs. 36% (43/121) in those who remained relapse free. On univariable analysis, CMV relapse was not associated with a significantly increased risk of death (unadjusted HR 1.59, 95% CI 0.92-2.75, P = 0.10). After controlling for age and transplanted organ type, findings were similar (adjusted HR 1.68, 95% CI 0.93-3.04, P = 0.09). Conclusion. Mortality rates following CMV remain high even in the valganciclovir era. In our study, we did not identify a significant relationship between the development of recurrent CMV disease and death. However, the complex nature of these patients, multiple layers of potential confounding and limited statistical power of our cohort make detection of small effects difficult. Future prospective studies evaluating the clinical efficacy of strategies to reduce recurrence are needed to further assess this relationship.
Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old boy returning fro... more Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old boy returning from a holiday with his family in Montana. His symptoms were initial diarrhoea and lethargy, with fever, rash, conjunctivitis, and arthralgia developing during the course of his illness. His condition worsened while he was at his local hospital, and he was transferred to the regional tertiary paediatric hospital. An initial echocardiogram was normal; however, repeat echocardiogram showed dilated coronary arteries with subsequent development of peeling of the skin on the hands and feet. The patient was started on intravenous immunoglobulin and high-dose aspirin and improved clinically. He was discharged home and remains under follow-up by the infectious diseases and cardiology teams.
Pediatric Infectious Disease Journal, Oct 21, 2022
Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19... more Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19 in high-risk patients ≥12 years of age. However, data for the use of these agents in children is limited. We reviewed 94 pediatric patients for whom early therapy was requested since the emergence of the Omicron variant and describe patient characteristics, treatment logistics and associated short-term events.
Article type : Original Article A multicenter study to define the epidemiology and outcomes of Cl... more Article type : Original Article A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.
Objectives Previous research has shown racial, ethnic, and socioeconomic disparities in provider ... more Objectives Previous research has shown racial, ethnic, and socioeconomic disparities in provider medical evaluations and reporting to child protective services (CPS) and law enforcement (LE) for cases of suspected child physical abuse. Our hospital standardized evaluation and reporting of high-risk bruising using a clinical pathway. We aimed to assess whether standardization impacted disparity. Methods We performed a retrospective observational study including children evaluated in the emergency department who had a social work consult for concern for child abuse or neglect between June 2012 and December 2019. From this group, we identified children with high-risk bruising. We compared outcomes (receipt of skeletal survey, CPS report, or LE report) before and after implementation of a standard bruising evaluation pathway to determine how the intervention changed practice among various racial, ethnic, and socioeconomic groups. Results During the study period, 2129 children presented to the ED and received a social work consult for child abuse or neglect. Of these, 333 had high-risk bruising. Children without private insurance had a higher risk of having a CPS (adjusted relative risk, 1.32; 95% confidence interval, 1.09–1.60) or LE (adjusted relative risk, 1.48; 95% confidence interval, 1.11–1.97) report prepathway, but not after pathway implementation. No significant associations were seen for race or ethnicity. Conclusions A standardized clinical pathway for identification and evaluation of high-risk bruising may help to decrease socioeconomic disparities in reporting high-risk bruising. Larger studies are needed to fully evaluate disparities in assessment and reporting of child abuse.
Improper use of maintenance intravenous fluids (IVFs) may cause serious hospitalacquired harm. We... more Improper use of maintenance intravenous fluids (IVFs) may cause serious hospitalacquired harm. We created an evidence-based clinical pathway to guide providers on the indications for IVF, its preferred composition, and appropriate clinical monitoring. METHODS: Pathway implementation was supported by the creation of an electronic order set (PowerPlan) and hospital-wide education. Outcomes were measured among pathway-eligible patients for the years before (
Journal of the Pediatric Infectious Diseases Society, Aug 10, 2021
Background Invasive candidiasis is the most common invasive fungal disease in children and adoles... more Background Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. Methods This multinational observational cohort study enrolled patients aged &gt;120 days and &lt;18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. Results Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was −7.1% points (95% CI: −13.1% to −2.4%), favoring echinocandins. The risk difference was −0.4% (95% CI: −7.5% to 6.7%) at 30 days. Conclusions In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. Clinical Trials Registration NCT01869829.
Journal of the Pediatric Infectious Diseases Society, Aug 25, 2020
We review the current knowledge of the epidemiology, clinical presentation, diagnostics, manageme... more We review the current knowledge of the epidemiology, clinical presentation, diagnostics, management, infection prevention, and preparedness for children with SARS-CoV-2 infections, listing resources, outlining research opportunities, and advocating for the unique needs of children in COVID-19 pandemic response.
Journal of the Pediatric Infectious Diseases Society
Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evide... more Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.
medRxiv (Cold Spring Harbor Laboratory), Mar 18, 2022
The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options f... more The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.
INTRODUCTION Ultrasound (US) imaging is preferred in the initial evaluation for children with sus... more INTRODUCTION Ultrasound (US) imaging is preferred in the initial evaluation for children with suspected nephrolithiasis; however, computed tomography (CT) continues to be used in this setting with resultant unnecessary ionizing radiation exposure. The study institution implemented a standardized clinical pathway to reduce rates of CT utilization for children with nephrolithiasis. OBJECTIVE The aim of this study was to evaluate the impact of this pathway on initial imaging strategies for children with suspected nephrolithiasis. STUDY DESIGN A standardized pathway was designed and implemented using a systematic quality improvement process. A suspected cohort was created using 'reason for study' search terms consistent with a nephrolithiasis diagnosis. A confirmed cohort of children with a final diagnosis of nephrolithiasis was derived from this suspected cohort. The primary outcome was CT use as the initial imaging study in children with suspected or confirmed nephrolithiasis presenting to the emergency department (ED) between October 2013 and February 2018. Comparisons were made before and after pathway implementation (October 2015). Secondary outcomes included rates of CT scan within 30 days, while balancing measures included rates of admission, ED length of stay, and return visits. RESULTS A total of 534 children with suspected (220 prepathway; 314 postpathway) and 90 children with confirmed (37 prepathway; 53 postpathway) nephrolithiasis were included. For the suspected cohort, CT scans performed as the initial imaging evaluation (9.2% vs 2.5%, P = 0.001) and at any time during the index visit (15.7% vs 5.7%, P = 0.001) decreased after pathway implementation. Within the confirmed cohort, a non-significant decrease in initial CT rates was observed after implementation. No differences were observed in admission rates or ED length of stay after implementation. A trend toward lower return visits to the ED was seen after pathway implementation (5.5% vs 2.2%, P = 0.058). DISCUSSION Within a tertiary care pediatric ED associated with a strong institutional experience with clinical pathways, initial CT rates were decreased after pathway implementation for children with suspected nephrolithiasis. While retrospective assessment of suspected disease is limited, this is one of the first studies to address imaging patterns for nephrolithiasis beyond the final discharge diagnosis, thus capturing a broader cohort of children. Children with suspected nephrolithiasis can be safely managed with an US-first approach, and postvisit CT scans are rarely necessary for management. CONCLUSIONS A standardized clinical pathway for suspected nephrolithiasis can reduce rates of initial and overall CT utilization without adversely impacting downstream care.
Background: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with ... more Background: Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for highrisk infants with CMV infection. Methods: We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT). Results: Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups. Conclusions: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.
Background. Infectious complications of chimeric antigen receptor (CAR) T-cell immunotherapy in c... more Background. Infectious complications of chimeric antigen receptor (CAR) T-cell immunotherapy in children and young adults have not been well described. Methods. Medical records of patients ≤26 years old receiving CD19 CAR T-cell infusion (CTI) at a single institution between 2014 and 2017 were reviewed. The number of infections per 100 days-at-risk (infection density) in the 90 days preceding and 0-28 and 29-90 days after CTI was calculated. Poisson regression and Cox analyses were utilized to identify risk factors for infections. Results. Eighty-three patients received CTI during the study period. Most patients (98%) had refractory or relapsed acute lymphoblastic leukemia (ALL). Infections occurred in 54% of patients in the 90 days before CTI (infection density, 1.23) and in 40% of patients in the first 28 days following CTI (infection density, 2.89). Infection density decreased to 0.55 in the 29-90 days post-CTI. Most infections were bacteremias (39%) or respiratory viral infections (43%). Pre-CTI risk factors associated with infection included prior hematopoietic cell transplantation (HCT), immunoglobulin G (IgG) level <400 mg/dL, and lymphodepletion other than cyclophosphamide plus fludarabine; post-CTI risk factors included higher-severity CRS and IgG <400 mg/dL. Conclusions. Infection rates in children and young adults receiving CD19 CAR T-cell therapy increase in the first month and then decline. Understanding types and timing of infections and contributing risk factors may help inform prophylactic and monitoring strategies. Specific attention should be given to patients with prior HCT, severe hypogammaglobulinemia, and severe CRS.
Purpose/Objectives: In August 2013, our institution implemented a standardized pathway for skin a... more Purpose/Objectives: In August 2013, our institution implemented a standardized pathway for skin and soft tissue infections (SSTI), based on national guidelines and local consensus. The pathway aimed to improve antimicrobial stewardship. We evaluated the impact of this pathway on antibiotic prescribing patterns for infections seen …
Censoring occurred at the time of death, loss to follow-up or 10 years. Univariable and multivari... more Censoring occurred at the time of death, loss to follow-up or 10 years. Univariable and multivariable hazard ratios (HR) were calculated using a Cox model, treating relapse and rejection following CMV as time-varying covariates. Results. Seventy-nine kidney, 52 heart, 34 liver and five liver-kidney transplant recipients were included. Sixty-two of 170 died, at a median of 3.8 years (interquartile range [IQR] 0.8-6.6 years). Median follow-up amongst the 108 survivors was 7.4 years (IQR 3.7-10 years) although 22 (13%) were censored before 3 years. CMV relapse occurred in 49/170 (29%), 67% within 6 months of treatment completion. Overall mortality amongst those who relapsed was 39% (19/49) vs. 36% (43/121) in those who remained relapse free. On univariable analysis, CMV relapse was not associated with a significantly increased risk of death (unadjusted HR 1.59, 95% CI 0.92-2.75, P = 0.10). After controlling for age and transplanted organ type, findings were similar (adjusted HR 1.68, 95% CI 0.93-3.04, P = 0.09). Conclusion. Mortality rates following CMV remain high even in the valganciclovir era. In our study, we did not identify a significant relationship between the development of recurrent CMV disease and death. However, the complex nature of these patients, multiple layers of potential confounding and limited statistical power of our cohort make detection of small effects difficult. Future prospective studies evaluating the clinical efficacy of strategies to reduce recurrence are needed to further assess this relationship.
Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old boy returning fro... more Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old boy returning from a holiday with his family in Montana. His symptoms were initial diarrhoea and lethargy, with fever, rash, conjunctivitis, and arthralgia developing during the course of his illness. His condition worsened while he was at his local hospital, and he was transferred to the regional tertiary paediatric hospital. An initial echocardiogram was normal; however, repeat echocardiogram showed dilated coronary arteries with subsequent development of peeling of the skin on the hands and feet. The patient was started on intravenous immunoglobulin and high-dose aspirin and improved clinically. He was discharged home and remains under follow-up by the infectious diseases and cardiology teams.
Pediatric Infectious Disease Journal, Oct 21, 2022
Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19... more Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19 in high-risk patients ≥12 years of age. However, data for the use of these agents in children is limited. We reviewed 94 pediatric patients for whom early therapy was requested since the emergence of the Omicron variant and describe patient characteristics, treatment logistics and associated short-term events.
Article type : Original Article A multicenter study to define the epidemiology and outcomes of Cl... more Article type : Original Article A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.
Objectives Previous research has shown racial, ethnic, and socioeconomic disparities in provider ... more Objectives Previous research has shown racial, ethnic, and socioeconomic disparities in provider medical evaluations and reporting to child protective services (CPS) and law enforcement (LE) for cases of suspected child physical abuse. Our hospital standardized evaluation and reporting of high-risk bruising using a clinical pathway. We aimed to assess whether standardization impacted disparity. Methods We performed a retrospective observational study including children evaluated in the emergency department who had a social work consult for concern for child abuse or neglect between June 2012 and December 2019. From this group, we identified children with high-risk bruising. We compared outcomes (receipt of skeletal survey, CPS report, or LE report) before and after implementation of a standard bruising evaluation pathway to determine how the intervention changed practice among various racial, ethnic, and socioeconomic groups. Results During the study period, 2129 children presented to the ED and received a social work consult for child abuse or neglect. Of these, 333 had high-risk bruising. Children without private insurance had a higher risk of having a CPS (adjusted relative risk, 1.32; 95% confidence interval, 1.09–1.60) or LE (adjusted relative risk, 1.48; 95% confidence interval, 1.11–1.97) report prepathway, but not after pathway implementation. No significant associations were seen for race or ethnicity. Conclusions A standardized clinical pathway for identification and evaluation of high-risk bruising may help to decrease socioeconomic disparities in reporting high-risk bruising. Larger studies are needed to fully evaluate disparities in assessment and reporting of child abuse.
Improper use of maintenance intravenous fluids (IVFs) may cause serious hospitalacquired harm. We... more Improper use of maintenance intravenous fluids (IVFs) may cause serious hospitalacquired harm. We created an evidence-based clinical pathway to guide providers on the indications for IVF, its preferred composition, and appropriate clinical monitoring. METHODS: Pathway implementation was supported by the creation of an electronic order set (PowerPlan) and hospital-wide education. Outcomes were measured among pathway-eligible patients for the years before (
Journal of the Pediatric Infectious Diseases Society, Aug 10, 2021
Background Invasive candidiasis is the most common invasive fungal disease in children and adoles... more Background Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. Methods This multinational observational cohort study enrolled patients aged &gt;120 days and &lt;18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. Results Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was −7.1% points (95% CI: −13.1% to −2.4%), favoring echinocandins. The risk difference was −0.4% (95% CI: −7.5% to 6.7%) at 30 days. Conclusions In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. Clinical Trials Registration NCT01869829.
Journal of the Pediatric Infectious Diseases Society, Aug 25, 2020
We review the current knowledge of the epidemiology, clinical presentation, diagnostics, manageme... more We review the current knowledge of the epidemiology, clinical presentation, diagnostics, management, infection prevention, and preparedness for children with SARS-CoV-2 infections, listing resources, outlining research opportunities, and advocating for the unique needs of children in COVID-19 pandemic response.
Journal of the Pediatric Infectious Diseases Society
Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evide... more Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.
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