Risk of serious bacterial infections in pediatric patients with hyperpyrexia.

Objectives: Hyperpyrexia has been associated with a greater prevalence of bacterial infections in the pediatric population, which prior to routine childhood vaccinations, has led to invasive testing and empiric antibiotic use for urinary tract infections, bacterial pneumonia, bacteremia, and bacterial meningitis. Since the implementation of routine childhood vaccinations, the prevalence of serious bacterial infections (SBIs) has declined. This study aims to determine if there is an association between hyperpyrexia and serious bacterial infections in well-appearing febrile pediatric patients presenting to the emergency department (ED). Methods: This is a cross-sectional study conducted between January 1, 2019, and December 31, 2019, at a single urban tertiary care pediatric ED. Patients were included if they were between 61 days and ≤18 years old presenting with a chief complaint of fever. Patients were excluded if they received antibiotics within 3 days of presentation, underwent surgical procedures within 2 weeks of presentation, had an ED visit for febrile illness within 2 weeks of study visit, were transferred from another institution, or were ill appearing. Prevalence of SBI was described and compared by presence of hyperpyrexia, age group, chronic medical condition, gender, and vaccination status. Logistic regression was used to analyze the association between SBIs and hyperpyrexia. Results: Of the 3862 charts reviewed, 2565 patients were included. The prevalence of SBI was 5.6%. A total of 413 patients presented with hyperpyrexia. Of the patients with hyperpyrexia, 31 (7.5%) had a serious bacterial infection. Hyperpyrexia was not significantly associated with SBIs in our logistic regression models (adjusted Odds Ratio 1.40, 95% confidence interval 0.92-2.12). Conclusions: Serious bacterial infections were uncommon in our population. There is no statistically significant association between hyperpyrexia and SBIs in well-appearing pediatric patients presenting to the ED with fever. The lack of a statistically significant association between hyperpyrexia and SBIs argues that clinicians should be cautious using hyperpyrexia as an independent risk factor for SBIs. More research is needed to identify independent and grouped SBI risk factors in well-appearing pediatric patients presenting to the ED.

Febrile infants aged ≤60 days: evaluation and management in the emergency department.

Emergency clinicians frequently provide care to febrile infants aged ≤60 days in the emergency department. In these very young infants, fever may be the only presenting sign of invasive bacterial infection and, if untreated, invasive bacterial infection can lead to severe outcomes. This issue reviews newer risk-stratification tools and the 2021 American Academy of Pediatrics clinical practice guideline to provide recommendations for the evaluation and management of febrile young infants. The most recent literature assessing the risk of concomitant invasive bacterial infection with urinary tract infections or positive viral testing is also reviewed.

Evaluation of Safety Measures at a Medical Summer Camp During the SARS-CoV-2 Pandemic.

INTRODUCTION: SARS-CoV-2 poses challenges for the safe delivery of a camp experience with a medically complex camper population. Multiple studies have investigated the effect of nonpharmaceutical interventions for preventing SARS-CoV-2 transmission in traditional summer camp settings, but none in the medical summer camp settings. Our objective was to describe and evaluate the nonpharmaceutical interventions on SARS-CoV-2 transmission rate in a medical summer camp setting. METHODS: This was a single-institution cross-sectional study conducted between June 2021 and August 2021 in a rural summer camp setting in upstate New York. Nonpharmaceutical interventions consisted of prearrival guidance on low-risk activities, obtaining negative SARS-CoV-2 polymerase chain reaction results within 72 h prior to arrival, adult SARS-CoV-2 vaccine mandate, universal masking mandate, small cohorts, daily symptom screening, and rapid testing on site. Primary cases were defined as an individual with a positive SARS-CoV-2 test result of any type while at camp or 2 wk after departure from camp without any known exposure at camp; secondary cases were defined as cases from potential exposures within camp. RESULTS: Two hundred and ninety-three campers were included. Nine individuals were tested owing to potentially infectious symptoms while at camp. Thirty-four campers were tested because they arrived from a county with an a priori intermediate level of SARS-CoV-2 community spread. Zero on-site rapid tests were positive for SARS-CoV-2. CONCLUSIONS: We describe the implementation of multilayered nonpharmaceutical interventions at a medical summer camp during the SARS-CoV-2 pandemic.

SARS-CoV-2 With Concurrent Respiratory Viral Infection as a Risk Factor for a Higher Level of Care in Hospitalized Pediatric Patients.

OBJECTIVE: As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care. DESIGN: A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database. SETTING: The medical ward and ICU of 67 participating hospitals. PATIENTS: Pediatric patients younger than 18 years hospitalized with SARS-CoV-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non-SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6-9.4; P < 0.01). CONCLUSIONS: This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2.

Characteristics of Afebrile Infants ≤60 Days of Age With Invasive Bacterial Infections.

OBJECTIVES: To describe the characteristics and outcomes of afebrile infants ≤60 days old with invasive bacterial infection (IBI). METHODS: We conducted a secondary analysis of a cross-sectional study of infants ≤60 days old with IBI presenting to the emergency departments (EDs) of 11 children's hospitals from 2011 to 2016. We classified infants as afebrile if there was absence of a temperature ≥38°C at home, at the referring clinic, or in the ED. Bacteremia and bacterial meningitis were defined as pathogenic bacterial growth from a blood and/or cerebrospinal fluid culture. RESULTS: Of 440 infants with IBI, 78 (18%) were afebrile. Among afebrile infants, 62 (79%) had bacteremia without meningitis and 16 (20%) had bacterial meningitis (10 with concomitant bacteremia). Five infants (6%) died, all with bacteremia. The most common pathogens were Streptococcus agalactiae (35%), Escherichia coli (16%), and Staphylococcus aureus (16%). Sixty infants (77%) had an abnormal triage vital sign (temperature <36°C, heart rate ≥181 beats per minute, or respiratory rate ≥66 breaths per minute) or a physical examination abnormality (ill appearance, full or depressed fontanelle, increased work of breathing, or signs of focal infection). Forty-three infants (55%) had ≥1 of the following laboratory abnormalities: white blood cell count <5000 or >15 000 cells per µL, absolute band count >1500 cells per µl, or positive urinalysis. Presence of an abnormal vital sign, examination finding, or laboratory test result had a sensitivity of 91% (95% confidence interval 82%-96%) for IBI. CONCLUSIONS: Most afebrile young infants with an IBI had vital sign, examination, or laboratory abnormalities. Future studies should evaluate the predictive ability of these criteria in afebrile infants undergoing evaluation for IBI.

Height of fever and invasive bacterial infection.

OBJECTIVE: We aimed to evaluate the association of height of fever with invasive bacterial infection (IBI) among febrile infants <=60 days of age. METHODS: In a secondary analysis of a multicentre case-control study of non-ill-appearing febrile infants <=60 days of age, we compared the maximum temperature (at home or in the emergency department) for infants with and without IBI. We then computed interval likelihood ratios (iLRs) for the diagnosis of IBI at each half-degree Celsius interval. RESULTS: The median temperature was higher for infants with IBI (38.8°C; IQR 38.4-39.2) compared with those without IBI (38.4°C; IQR 38.2-38.9) (p<0.001). Temperatures 39°C-39.4°C and 39.5°C-39.9°C were associated with a higher likelihood of IBI (iLR 2.49 and 3.40, respectively), although 30.4% of febrile infants with IBI had maximum temperatures <38.5°C. CONCLUSIONS: Although IBI is more likely with higher temperatures, height of fever alone should not be used for risk stratification of febrile infants.

Febrile Infants ≤60 Days Old With Positive Urinalysis Results and Invasive Bacterial Infections.

OBJECTIVES: We aimed to describe the clinical and laboratory characteristics of febrile infants ≤60 days old with positive urinalysis results and invasive bacterial infections (IBI). METHODS: We performed a planned secondary analysis of a retrospective cohort study of febrile infants ≤60 days old with IBI who presented to 11 emergency departments from July 1, 2011, to June 30, 2016. For this subanalysis, we included infants with IBI and positive urinalysis results. We analyzed the sensitivity of high-risk past medical history (PMH) (prematurity, chronic medical condition, or recent antimicrobial receipt), ill appearance, and/or abnormal white blood cell (WBC) count (<5000 or >15 000 cells/µL) for identification of IBI. RESULTS: Of 148 febrile infants with positive urinalysis results and IBI, 134 (90.5%) had bacteremia without meningitis and 14 (9.5%) had bacterial meningitis (11 with concomitant bacteremia). Thirty-five infants (23.6%) with positive urinalysis results and IBI did not have urinary tract infections. The presence of high-risk PMH, ill appearance, and/or abnormal WBC count had a sensitivity of 53.4% (95% confidence interval: 45.0-61.6) for identification of IBI. Of the 14 infants with positive urinalysis results and concomitant bacterial meningitis, 7 were 29 to 60 days old. Six of these 7 infants were ill-appearing or had an abnormal WBC count. The other infant had bacteremia with cerebrospinal fluid pleocytosis after antimicrobial pretreatment and was treated for meningitis. CONCLUSIONS: The sensitivity of high-risk PMH, ill appearance, and/or abnormal WBC count is suboptimal for identifying febrile infants with positive urinalysis results at low risk for IBI. Most infants with positive urinalysis results and bacterial meningitis are ≤28 days old, ill-appearing, or have an abnormal WBC count.

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection.

OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI). METHODS: We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated. RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age <21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per µL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores ≥2. CONCLUSIONS: Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per µL have a low probability of IBI.

Evaluation and management of the febrile young infant in the emergency department

Among young infants presenting with fever, untreated serious bacterial infections can have severe outcomes, so a full sepsis workup is often recommended but may not be necessary. This issue reviews the use of novel diagnostic tools such as procalcitonin, C-reactive protein, and RNA biosignatures as well as new risk stratification tools such as the Step-by-Step approach and the Pediatric Emergency Care Applied Research Network prediction rule to determine which febrile young infants require a full sepsis workup and to guide the management of these patients in the emergency department. The most recent literature assessing the risk of concomitant bacterial meningitis with urinary tract infections and the role for viral testing, specifically herpes simplex virus and enterovirus, are also reviewed.

Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. METHODS: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections.

OBJECTIVE: To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis). STUDY DESIGN: Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt. RESULTS: Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths. CONCLUSIONS: Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI.

Risk Stratification of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture.

: media-1vid110.1542/5840460609001PEDS-VA_2018-1879Video Abstract OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing. METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a complex chronic condition or if data for any component of the Rochester or modified Philadelphia criteria were missing. RESULTS: Overall, 135 infants with IBI (118 [87.4%] with bacteremia without meningitis and 17 [12.6%] with bacterial meningitis) and 249 controls were included. The sensitivity of the modified Philadelphia criteria was higher than that of the Rochester criteria (91.9% vs 81.5%; P = .01), but the specificity was lower (34.5% vs 59.8%; P < .001). Among 67 infants >28 days old with IBI, the sensitivity of both criteria was 83.6%; none of the 11 low-risk infants had bacterial meningitis. Of 68 infants ≤28 days old with IBI, 14 (20.6%) were low risk per the Rochester criteria, and 2 had meningitis. CONCLUSIONS: The modified Philadelphia criteria had high sensitivity for IBI without routine CSF testing, and all infants >28 days old with bacterial meningitis were classified as high risk. Because some infants with bacteremia were classified as low risk, infants discharged from the emergency department without CSF testing require close follow-up.

Time to Pathogen Detection for Non-ill Versus Ill-Appearing Infants ≤60 Days Old With Bacteremia and Meningitis.

OBJECTIVES: We sought to determine the time to pathogen detection in blood and cerebrospinal fluid (CSF) for infants ≤60 days old with bacteremia and/or bacterial meningitis and to explore whether time to pathogen detection differed for non-ill-appearing and ill-appearing infants. METHODS: We included infants ≤60 days old with bacteremia and/or bacterial meningitis evaluated in the emergency departments of 10 children's hospitals between July 1, 2011, and June 30, 2016. The microbiology laboratories at each site were queried to identify infants in whom a bacterial pathogen was isolated from blood and/or CSF. Medical records were then reviewed to confirm the presence of a pathogen and to extract demographic characteristics, clinical appearance, and the time to pathogen detection. RESULTS: Among 360 infants with bacteremia, 316 (87.8%) pathogens were detected within 24 hours and 343 (95.3%) within 36 hours. A lower proportion of non-ill-appearing infants with bacteremia had a pathogen detected on blood culture within 24 hours compared with ill-appearing infants (85.0% vs 92.9%, respectively; P = .03). Among 62 infants with bacterial meningitis, 55 (88.7%) pathogens were detected within 24 hours and 59 (95.2%) were detected within 36 hours, with no difference based on ill appearance. CONCLUSIONS: Among infants ≤60 days old with bacteremia and/or bacterial meningitis, pathogens were commonly identified from blood or CSF within 24 and 36 hours. However, clinicians must weigh the potential for missed bacteremia in non-ill-appearing infants discharged within 24 hours against the overall low prevalence of infection.

Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments.

OBJECTIVES: To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities. STUDY DESIGN: Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data. RESULTS: Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone. CONCLUSIONS: For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.

Epidemiology of preoperative hematologic assessment of children cared for in a pediatric emergency department.

OBJECTIVE: To assess frequency of preoperative hematologic testing in a tertiary care pediatric emergency department (PED) and how often these values predict clinical outcome or change management decisions. METHODS: Single-center retrospective cohort study in a tertiary-care children's hospital PED. Patients 0-18years old, presenting between July 1, 2009-July 1, 2011, ultimately undergoing a surgical procedure within 48h of presentation were included. Patients were defined as having "preoperative" hematologic assessment if these studies were performed solely because the child was going to the operative suite. Patients who met trauma team activation criteria, underwent neurosurgical procedures, or had laboratory studies performed prior to PED arrival were excluded. The primary outcome was the prevalence of preoperative laboratory assessment. RESULTS: 528 children were included, of whom 301 (57%) underwent preoperative hematologic laboratory evaluations. Of these 301 patients, 115 (38%) had abnormal hematologic parameters, and only 3 (1%) of these patients had their perioperative management changed. One additional child had intraoperative bleeding that required blood products but did not undergo preoperative hematologic assessment. All four children had medical histories that would have identified their risk for perioperative bleeding events. CONCLUSION: Preoperative hematologic laboratory assessment occurs frequently in children initially cared for in a tertiary care pediatric emergency department who subsequently undergo operative interventions. Although age-based abnormal hematologic values are often found, rarely are these abnormalities clinically significant. This study suggests that children cared for in a PED without a history concerning for an increased risk of perioperative bleeding does not require preoperative hematologic assessment.

Management of the Febrile Young Infant: Update for the 21st Century.

Infants aged 90 days or younger with fever are frequently evaluated in the pediatric emergency department. Physical examination findings and individual laboratory investigations are not reliable to differentiate benign viral infections from serious bacterial infections in febrile infants. Clinical prediction models were developed more than 25 years ago and have high sensitivity but relatively low specificity to identify bacterial infections in febrile infants. Newer laboratory investigations such as C-reactive protein and procalcitonin have favorable test characteristics compared with traditional laboratory studies such as a white blood cell count. These novel biomarkers have not gained widespread acceptance because of lack of robust prospectively collected data, varying thresholds to define positivity, and differing inclusion criteria across studies. However, C-reactive protein and procalcitonin, when combined with other patient characteristics in the step-by-step approach, have a high sensitivity for detection of serious bacterial infection. The RNA biosignatures are a novel biomarker under investigation for detection of bacterial infection in febrile infants.

Previous Looks May Be Deceiving: Point-of-Care Ultrasound to Diagnose Hypertrophic Cardiomyopathy Despite a Previously Normal Echocardiogram.

We describe a case of a 17-year-old boy presenting to the emergency department following a presyncopal episode with exertion. His medical history is significant for a murmur, which was determined to be benign in nature after a normal echocardiogram at 12 years of age. His workup in the emergency department included an electrocardiogram, which was significant for left ventricular hypertrophy, and a point-of-care ultrasound, which was significant for severe concentric left ventricular hypertrophy with diastolic dysfunction consistent with hypertrophic cardiomyopathy.

Klebsiella pneumonia liver abscess syndrome: Case presentation to a college student health clinic.

The authors describe a case of Klebsiella pneumoniae liver abscess (KPLA) in a student presenting to a university student health center. The authors also provide a review of KPLA and invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS), including epidemiology, common clinical manifestations, standard diagnostic work-up, management options, and potential complications.

AKI in Children Hospitalized with Nephrotic Syndrome.

BACKGROUND AND OBJECTIVES: Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition. RESULTS: AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001). CONCLUSIONS: AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.