Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-ß-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. CLINICAL TRIALS REGISTRATION: NCT02220790.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

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 >120 days and <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.

Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C. METHODS: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently. RESULTS: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms (z score ≥2.5), and 4 (8%) had coronary dilation (z score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%). CONCLUSIONS: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.

Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort.

BACKGROUND: Adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had high rates of thrombosis. A novel condition in children infected with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), has limited data on their prothrombotic state or need for thromboprophylaxis. OBJECTIVES: We aimed to analyze the prothrombotic state using coagulation profiles, rotational thromboelastometry (ROTEM) parameters and clinical outcomes, to determine if this could aid in risk stratification for thromboprophylaxis. METHODS: This analysis included patients (<21 years of age) with a diagnosis of MIS-C (n = 40) and controls (presenting with suspicion of MIS-C but later ruled out; n = 26). RESULTS: MIS-C patients had higher levels of inflammatory markers including D-dimer (p < .0001), compared with controls, along with evidence of hypercoagulability on ROTEM with elevated evaluation of fibrinogen activity (FIBTEM) maximum clot firmness (MCF) (p < .05). For MIS-C patients with D-dimers >1000 ng/ml, there was a significant correlation of FIBTEM MCF (p < .0001) with a mean value of 37.4 (standard deviation 5.1). D-dimer >2144 ng/ml was predictive of intensive care unit admission (area under the curve [AUC] 0.80; 95% confidence interval, 0.60-0.99; p < .01; sensitivity: 82%, specificity: 75%), and elevated FIBTEM MCF (AUC 1 for >2500 ng/ml). MIS-C patients (50%) received enoxaparin thromboprophylaxis (in addition to aspirin) with significant improvement in their inflammatory and ROTEM parameters upon outpatient follow-up; none developed symptomatic thrombosis. CONCLUSIONS: Despite an observed prothrombotic state, none of the MIS-C patients (on aspirin alone or in combination with enoxaparin) developed symptomatic thrombosis. ROTEM, in addition to coagulation profiles, may be helpful to tailor thromboprophylaxis in critically ill MIS-C patients.

Gonococcal osteomyelitis in a pediatric patient with disseminated gonococcal infection: Implications for antimicrobial management.

We report a case of a female teenager with gonococcal septic arthritis of the right shoulder that also caused osteomyelitis of the humeral head. Infection with Neisseria gonorrhoeae is a frequently diagnosed sexually transmitted infection in the sexually active teenage population and disseminated gonococcal infection (DGI) is the most common systemic manifestation of acute gonorrhea. DGI commonly involves acute arthritis, tenosynovitis and dermatitis with less common complications of endocarditis, hepatitis and meningitis. In contrast, osteomyelitis has only rarely been reported as a result of gonococcal infection. Clinicians need to be aware of this unusual manifestation of DGI as a prolonged duration of antimicrobial treatment may be needed to assure complete resolution of this infection.

Early Experience of COVID-19 in a US Children's Hospital.

OBJECTIVES: We aim to describe the demographics, clinical presentation, hospital course, and severity of pediatric inpatients with coronavirus disease 2019 (COVID-19), with an emphasis on healthy, immunocompromised, and chronically ill children. METHODS: We conducted a single-center retrospective cohort study of hospitalized children aged younger than 22 years with COVID-19 infection at Steven and Alexandra Cohen Children's Medical Center at Northwell Health. Cases were identified from patients with fever and/or respiratory symptoms who underwent a nucleic acid amplification-based test for severe acute respiratory syndrome coronavirus 2. RESULTS: Sixty-five patients were identified. The median age was 10.3 years (interquartile range, 1.4 months to 16.3 years), with 48% of patients older than 12 years and 29% of patients younger than 60 days of age. Fever was present in 86% of patients, lower respiratory symptoms or signs in 60%, and gastrointestinal symptoms in 62%. Thirty-five percent of patients required ICU care. The white blood cell count was elevated in severe disease (P = .0027), as was the C-reactive protein level (P = .0192), compared with mild and moderate disease. Respiratory support was required in 34% of patients. Severity was lowest in infants younger than 60 days of age and highest in chronically ill children; 79% of immunocompromised children had mild disease. One death was reported. CONCLUSIONS: Among children who are hospitalized for COVID-19, most are younger than 60 days or older than 12 years of age. Children may have severe infection requiring intensive care support. The clinical course of immunocompromised patients was not more severe than that of other children. Elevated white blood cell count and C-reactive protein level are associated with greater illness severity.

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.

Coccidioidal Meningitis in New York Traced to Texas by Fungal Genomic Analysis.

A child developed hydrocephalus. Sixteen months later, it was discovered to be a complication of coccidioidal meningitis. The infection's source was uncertain until genomic analysis of the fungal isolate identified its origin to be a visit to Beeville, Texas. Improved national reporting of cases of coccidioidomycosis might reduce diagnostic delays.

Transfusion-transmitted babesiosis leading to severe hemolysis in two patients with sickle cell anemia.

The intracellular parasites Babesia microti and Babesia duncani can be transmitted by blood transfusion and cause severe life-threatening hemolytic anemia in high-risk patients, including those with sickle cell disease. The rarity of the diagnosis, as well as its similar clinical presentation to delayed hemolytic transfusion reaction, may lead to a delay in diagnosis, as well as inappropriate treatment with steroids or other immunosuppressive agents. The morbidity caused by this disease in especially vulnerable populations justifies the need for a universal blood-screening program in endemic areas.

Varicella in a Previously Immune Patient With Leukemia.

Infection with varicella-zoster virus (VZV) in oncology patients can result in severe disease with an increased risk of morbidity and mortality [1, 2]. Among patients on cancer chemotherapy, only nonimmune persons are considered to be susceptible to varicella [1]. We present a case of varicella in a child with leukemia that occurred despite immunity as defined by 2 doses of varicella vaccine and documentation of positive VZV immunoglobulin G titer before initiation of chemotherapy.

Comparison of the clinical features of children hospitalized with pandemic 2009 A:H1N1 and seasonal influenza.

INTRODUCTION: We compared the demographics, clinical presentation, course and outcome of children hospitalized with pandemic A:H1N1 and seasonal influenza. METHODS: Sixty seven patients hospitalized from April 1st through August 31st 2009 with pandemic A:H1N1 influenza were enrolled. Two seasonal influenza cohorts were identified: 38 inpatients from January 1st 2004 through March 31st 2009, diagnosed by viral culture or direct fluorescent antibody testing; and 42 inpatients from January 1st 2007 through December 31st 2008 diagnosed via a rapid test. The two seasonal cohorts were not significantly different and were combined. RESULTS: Patients with pandemic influenza were older (median age 6.5 years versus 1.3 years, P <.0001); were more often black (46% versus 23%, P <.0002); more frequently had an underlying condition (72% versus 49% P <.0049); and more often had wheezing (57% versus 16%, P <.0001). CONCLUSION: There was no significant difference between the groups in measures of severity during hospitalization.

Sling plication for recurrent stress urinary incontinence.

OBJECTIVES: : Management of recurrent stress urinary incontinence (SUI) after synthetic mid-urethral sling placement is a challenging clinical dilemma. This case series describes a safe, minimally invasive treatment option for recurrent SUI after failure of the primary mid-urethral sling procedure. METHODS: : Twenty women with recurrent SUI after previous synthetic mid-urethral sling placement underwent plication of the sling with 2-0 polyester suture under intravenous sedation with an intra-operative cough stress test between December 2004 and December 2008. A retrospective chart review was performed to obtain pertinent preoperative and postoperative data. RESULTS: : Nine of the patients had prior retropubic synthetic mid-urethral slings. The other 11 women had transobturator mid-urethral slings, 10 of whom had slings via the outside-in approach and 1 had a single-incision mini-sling placed. The mean patient age was 59.8 years (range 38-83 years). Sling plication was performed at a median of 159.5 days after initial sling placement (range 26-2090 days). Overall 85% of patients had subjective improvement in SUI after sling plication with a median follow-up of 54.5 days (range 29-972 days). Those patients with prior retropubic slings had a 100% improvement rate compared to 72% improvement with prior obturator slings (P = 0.22). The subjective cure rate was 65%, 88% for the retropubic slings and 45% for the transobturator slings (P = 0.07). There were no complications. CONCLUSIONS: : Midline plication of previously placed synthetic mid-urethral slings is a safe and effective method of treating recurrent SUI.

Staphylococcus aureus nasal colonization among pediatric cystic fibrosis patients and their household contacts.

BACKGROUND: Little is known about the prevalence of Staphylococcus aureus nasal colonization and the epidemiology of methicillin-susceptible and methicillin-resistant S. aureus (MRSA) among cystic fibrosis (CF) patients and their household members. OBJECTIVES: We sought to determine the epidemiology of S. aureus among children and adolescents with CF and their household members. METHODS: Three CF centers enrolled case subjects with at least 1 MRSA-positive respiratory tract culture from 2001 to 2006 and control subjects with MRSA-negative cultures. S. aureus isolates from the anterior nares of CF subjects and their household members were assessed for staphylococcal chromosomal cassette (SCC) mec type. Strain similarity was determined by pulsed-field gel electrophoresis. RESULTS: S. aureus nasal colonization occurred in 52.4% (22/42), 27.0% (17/63), and 25.0% (72/288) of case, control, and household participants, respectively. Case subjects and their contacts were more likely to harbor MRSA in their nares and be from a multipatient CF family. Of 31 MRSA strains, 10 (32.3%) were SCCmec type IVa, associated with community-acquisition. Overall, 27.6% of 98 households had > or =2 members colonized with closely related isolates. Household members were equally likely to be colonized with closely related strains of MRSA (20/31, 65%) versus MSSA (38/80, 48%). CONCLUSIONS: This study demonstrated that household members of CF children harbor both MSSA and MRSA, including CA-MRSA, and that S. aureus is transmitted within CF households. Carriage of S. aureus by household members of CF children may have implications for infection control and treatment strategies. Future studies should monitor the distribution and virulence of SCCmecA types in patients with CF.

A reliable, valid instrument to assess patient knowledge about urinary incontinence and pelvic organ prolapse.

The objective of this study is to develop a reliable, validated questionnaire to assess patient knowledge about urinary incontinence (UI) and pelvic organ prolapse (POP). We designed a written questionnaire comprised of UI and POP scales and administered it to 133 gynecologic and 61 urogynecologic patients. We performed a principal components factor analysis for UI and POP items and assessed construct validity, internal consistency, and stability of each scale. For both scales, mean total urogynecologic group scores exceeded those for gynecologic patients (P values < 0.001), suggesting construct validity. Both scales had excellent internal consistency (Cronbach's alpha > 0.8). Mean test scores were slightly higher upon retest (UI, 0.46, P = 0.046; POP, 0.33, P = 0.126). Pearson's correlation between initial and repeat scores was high for UI (0.675) and POP scales (0.940), indicating questionnaire stability. We developed a reliable, valid instrument for assessing patient knowledge about UI and POP.

Surgery for stress urinary incontinence in the United States: does race play a role?

The objective of this study was to evaluate the prevalence, demographics and complications of stress urinary incontinence (SUI) surgery across races in the United States (US) in 2003. We hypothesized that there would be racial differences in surgical rates. Data from the 2003 National Census and National Hospital Discharge Survey were used. Continuous variables were tested for statistical significance by one-way analysis of variance and categorical variables by chi2 analysis. 129,778 women underwent SUI surgery in the US in 2003, a rate of 12 surgical procedures per 10,000 women (95% CI 10-14). By race, rates (per 10,000 women, 95% CI) of SUI surgery were: ten (7-12) in white women, three (0-9) in black women, and six (0-13) in women of other races. Racial disparities in the receipt of SUI surgery may exist.

The age distribution, rates, and types of surgery for stress urinary incontinence in the USA.

The objective of this study was to describe the distribution of stress urinary incontinence (SUI) surgery across age groups in the USA in 2003. Patients were grouped into four age categories: reproductive, perimenopausal, postmenopausal, and elderly. Data from the 2003 National Hospital Discharge Survey and National Census were used to estimate surgical rates by age group. In 2003, 129,778 women underwent 165,776 surgical procedures for SUI. Of these women, 12.2, 53.0, 30.4, and 4.5% belonged to reproductive, perimenopausal, postmenopausal, and elderly age groups, respectively. Surgical rates (per 10,000 women) were 4, 17, 19, and 9 in these age groups, respectively. Complications occurred most frequently in reproductive age women. Overall, SUI surgical rates were similar for perimenopausal and postmenopausal women and exceeded that in the elderly population. The greatest percentage of surgical procedures occurred in perimenopausal women. Women at all stages of reproductive life may seek surgical treatment for SUI.

The age distribution, rates, and types of surgery for pelvic organ prolapse in the USA.

The objective of this study was to describe the distribution of pelvic organ prolapse (POP) surgery across age groups in the USA in 2003. Patients were grouped into four age categories: Reproductive age, perimenopausal, postmenopausal, and elderly. Data from the 2003 National Hospital Discharge Survey and National Census were used to estimate surgical rates by age group. In 2003, 199,698 women underwent a total of 311,587 surgical procedures for POP. Prolapse surgical rates (per 10,000 women) were 7, 24, 31, and 17 in reproductive age, perimenopausal, postmenopausal, and elderly age groups, respectively. Surgical complications occurred in 28.8, 19.6, 18.6, and 22.1% of women in these age groups, respectively. Mortality was uncommon. Although often considered a condition of the elderly, this study suggests that pelvic organ prolapse is a condition affecting women across the reproductive life cycle and for which women of all ages seek surgical treatment.