Preceding Clinical Events in High-risk, Postoperative, Pediatric Cardiac Patients-A Novel Association With Bacteremia.

Objective: Blood stream infections (BSIs) are well described in pediatric cardiac intensive care units (PCICU). We noted that postoperative high-risk patients may develop BSI after a preceding clinical event (PCE). The study aim was to investigate whether high-risk patients who developed bacteremia experienced more PCEs than a similar group of high-risk patients. Design: Retrospective case-control study. Setting: Referral pediatric center. Patients: We enrolled patients who developed bacteremia from March 2010 to November 2019, after undergoing open-heart surgery at a pediatric center. The control group was comprised of case-matched patients with immediate consecutive same surgery. Interventions: None. Measurements: We recorded operative data, common risk factors, postoperative indicators of organ dysfunction, mortality, and PCEs 72 to 24 h before bacteremia emerged. Main results: A total of 200 patients were included (100 with bacteremia and 100 controls). Key demographic and operative parameters were matched. Bacteremia emerged on average on postoperative day 12.8. Skin-associated Gram-positive bacteria were cultured in 10% and Gram-negative bacteria in 84% of the patients. Average central-venous lines (CVL) duration was 9.5 ± 8.4 days. Postoperatively (72 h), indicators of organ dysfunction were significantly worse in patients with bacteremia, with a higher rate of postoperative complications during PCICU length-of-stay (LOS). In the bacteremia group, 72 to 24 h prior to the development of bacteremia, 92 (92%) PCEs were recorded, as compared to 21 (21%) in controls during their entire LOS (odds ratio [OR] 43.3, confidence interval [CI] 18.2-103.1, P < .0001). Conclusions: We propose a 3-hit model demonstrating that high-risk patients undergoing open-heart surgery have significantly higher risk for bacteremia after a PCE.

Definitive antibiotic treatment with a third-generation cephalosporin and with piperacillin-tazobactam worked well for some children with Serratia bacteraemia.

AIM: This study aimed to describe epidemiological and clinical characteristics of Serratia bacteraemia and to identify factors associated with mortality. METHODS: The microbiology database of Schneider Children's Medical Centre of Israel was examined for Serratia marcescens positive blood cultures, between January 2007 and May 2020. Demographic, clinical and microbial characteristics were analysed. RESULTS: Of the 81 patients files that met the inclusion criteria, 64 (80%) were of patients hospitalised in paediatric intensive care units. The median age was 78 days and 54% were male. In-hospitalisation mortality was 26%, 62% died under 90 days old. Underlying conditions including prematurity, congenital cardiac defects and malignancies were noted in 95% of patients. Prior to the bloodstream infections, 62% of patients underwent procedures, 64% were on ventilatory support and 77% had central lines. Thrombocytopenia and elevated C-reactive protein levels were found in 60% of the children. Twenty-eight children received definitive monotherapy as either piperacillin-tazobactam or a third-generation cephalosporin; survival rates were similar between the two antibiotic treatment groups. CONCLUSION: In our cohort, 26% died. Death was more common in young infants. Mortality was associated with hospitalisation in intensive care units and thrombocytopenia. Survival rates following definitive monotherapy were similar for patients treated with piperacillin-tazobactam and those treated with third-generation cephalosporin.

COVID-19 infection in pediatric patients treated for cancer.

BACKGROUND: COVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial. AIM: To describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment. METHODS: Clinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center. RESULTS: Eighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19. CONCLUSION: In pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.

Vacuum-Assisted Closure for the Treatment of Deep Sternal Wound Infection After Pediatric Cardiac Surgery.

OBJECTIVES: Vacuum-assisted closure is being increasingly used to treat deep sternal wound infection following cardiac surgery, but most of the data refer to adults. This study investigated the safety and efficacy of vacuum-assisted closure in pediatric patients. DESIGN: Retrospective file review. SETTING: Tertiary pediatric medical center. PATIENTS: All children with deep sternal wound infection treated with vacuum-assisted closure in 2003-2016. INTERVENTIONS: Epidemiological, clinical, and microbiological data were collected from the medical records. MEASUREMENTS AND MAIN RESULTS: The cohort included 50 patients (0.9% of cardiac patients operated during the study period) of median age 6.5 months (interquartile range, 2-12.75 mo; range, 1 wk to 14 yr) and median weight 5.1 kg (interquartile range, 4-9.75 kg). The most frequent heart defects were tetralogy of Fallot (22%) and ventricular septal defect (20%); 38% of patients had cyanotic heart disease. Deep sternal wound infections appeared a median of 10 days postoperatively (interquartile range, 7-14 d; range 3-100 d). Vacuum-assisted closure was applied a median of 13 days postoperatively (interquartile range, 10-18.5 d; range, 5-103 d) for a median duration of 10 days (interquartile range, 7-13.25 d; range, 1-21 d). Wound cultures were positive in 48 patients (96%); most isolates were Gram-positive (76%). The main bacterial pathogen was methicillin-susceptible Staphylococcus aureus (61%). Most patients were treated with cloxacillin for a median of 38 days (interquartile range, 28-42 d; range, 9-189 d). There were no statistically significant differences in clinical or treatment characteristics between bacteremic (56%) and nonbacteremic patients. Compared with older patients, infants less than 3 months old (36%) had a significantly longer hospitalization time (41 vs 25 d; p = 0.001) and higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category (3 vs 2; p = 0.003). All cases except one (contact dermatitis) were uneventful. In 10 patients, wounds were closed surgically after vacuum-assisted closure. Two patients required a pectoralis flap, both treated before 2005. One of the two deaths was infection-related. CONCLUSIONS: Vacuum-assisted closure is a feasible treatment option of deep sternal wound infection after pediatric cardiac surgery and was not associated with independent morbidity.

Leukemoid reaction in the pediatric population: etiologies, outcome, and implications.

Leukemoid reaction (WBC > 30,000/µL) may indicate significant medical conditions, mostly infectious. Prompted by the lack of population-based data on the presentation, characteristics, and necessary workup in children with leukemoid reaction, we searched the database of a tertiary pediatric medical center for all children presented with at least one WBC count of ≥ 30,000/µL in 2009-2014. Demographic, clinical, and laboratory parameters were recorded. Children admitted with WBC < 30,000/µL served as controls. Pneumonia was the most common diagnosis in the leukemoid reaction group, with a 5.5-fold higher prevalence of pleuropneumonia than in the control group. The leukemoid group had a longer average hospital stay (7.5 vs. 5.5 days). Patients with WBC ≥ 50,000/µL had a sixfold higher rate of leukemia than patients with a lower count. There was a significant association of leukemia with low platelet count, low levels of C-reactive protein, and high levels of uric acid and lactate dehydrogenase. CONCLUSION: Children presented with a leukemoid reaction are at high risk of pneumonia, especially pleuropneumonia, and a long hospital stay. Those with WBC ≥ 50,000/µL have a sixfold higher risk of leukemia. For prompt diagnosis, clinicians should be aware of the variables associated with leukemia. What is Known: • Leukemoid reaction has been associated with infectious diseases. • Leukemoid reaction at presentation in adults is correlated with high morbidity and mortality. What is New: • Children with leukemoid reaction are at high risk of pleuropneumonia. • We did not observe increased mortality in children with a leukemoid reaction.

Dual versus Triple Antibiotics Regimen in Children with Perforated Acute Appendicitis.

INTRODUCTION: Acute appendicitis is the most common emergency condition in pediatric surgery. Historically, a triple-antibiotic therapy consisted of ampicillin, gentamicin, and clindamycin has been used postoperatively for perforated appendicitis. According to recently published trials, dual therapy consists of ceftriaxone and metronidazole only, offers a more efficient and cost-effective antibiotic management compared with triple therapy. Based on these results, our department applied dual antibiotic therapy for children with perforated appendicitis that underwent appendectomy from 2009 and forth. AIM: The aim of our study was to compare postoperative outcomes between patients treated with triple therapy (ampicillin, gentamicin, and metronidazole) (group A) versus dual therapy (ceftriaxone and metronidazole) (group B). METHODS: Clinical and laboratory data were retrospectively collected by review of the medical records for all children who underwent appendectomy for the perforated appendix at the Schneider Children's Medical Center of Israel, a tertiary pediatric care center between 2007 and 2011. Children with perforated appendicitis received antibiotic therapy in accordance with the hospital's guidelines that were valid at the time the surgery took place. In the first period (years 2007-2009) (group A) a triad of ampicillin, gentamicin, and metronidazole and the second period (2009-2011) (group B) dual therapy consists of ceftriaxone and metronidazole. The two groups were compared for outcome and complications, such as wound infections, changing of antibiotic therapy, and length of stay. RESULTS: During the study period 1,203 patients underwent an appendectomy. Of these, 175 patients were diagnosed with perforated appendix and were treated with postoperative antibiotic's regimen. Group A and group B consisted of 89 and 86 patients, respectively. The two groups were not different significantly in terms of demographic data, length of stay, or readmission rates. However, more rates of wound infection and changing of antibiotic therapy were seen in group B, although not statistically significant (p = 0.064). CONCLUSION: Dual antibiotic therapy for perforated appendicitis is a cost-effective and efficient mode of therapy compared with triple-antibiotic's regimen. However, prospective studies are required to determine whether this policy is associated with higher rates of wound infections and change in antibiotic therapy.

[ANTI-N-METHYL-D-ASPARTATE (NMDA) ENCEPHALITIS: THE ISRAELI PEDIATRIC MULTI-CENTER EXPERIENCE].

INTRODUCTION: Anti-N-methyl-D-aspartate (NMDA) encephalitis is a disorder characterized by acute neuro-psychiatric symptoms, appearing mostly after a recent febrile disease, with a gradual progressive course, associated with laboratory or radiologic evidence of active inflammation. Many of the patients will present with a continuous neuro-cognitive disorder which could lead to major morbidity and even mortality. It was recently reported that this disorder can present at childhood as a primary disease or as a secondary complication of herpes simplex infection. Early diagnosis and treatment have significantly improved the patients' prognosis and prevented chronic complications. We will present six pediatric patients at ages 1-14 years, followed from 2011-2014 in Schneider Children's Medical Center and Assaf Harofeh Medical Center due to acute encephalitis, with a clinical course under suspicion for anti-NMDA encephalitis. The article will review the clinical and diagnostic dilemmas and suggested guidelines. Pediatricians should be aware of this new emerging syndrome.

Clinical Impact of ß-Lactamase-producing Enterobacteriaceae in Sputum of Cystic Fibrosis Patients.

This case series describes 18 cystic fibrosis (CF) patients of a 135-patient CF center cohort with extended spectrum ß-lactamase-producing Enterobacteriaceae, from 2003 to 2012. Four had chronic infection. Prevalence increased annually from 0 to 6.35%. Risk factors compared with the 2010 CF center cohort included continuous inhaled antibiotics (P = 0.014) and courses of intravenous antibiotics during the year before first isolation (P = 0.009). Hospitalization rates were 1.05/year and 0.47/year preinfection and postinfection, respectively (P = 0.02). Slope of forced expiratory volume at 1 second% predicted remained unchanged during 12 months.

Extremely elevated C-reactive protein levels are associated with unfavourable outcomes, including death, in paediatric patients.

AIM: The aim of this study was to investigate the clinical significance of extremely elevated C-reactive protein (CRP) levels in hospitalised children. METHODS: We searched the electronic database of a tertiary paediatric medical centre for all patients admitted in 2010-2013 with a CRP of ≥ 30 mg/dL, and these comprised the study group. The controls were the other admissions. Data were collected on demographics, admission details, pre-existing conditions, discharge diagnosis, laboratory results and clinical outcomes. RESULTS: Our study group comprised 435 (0.72%) of the 59,997 patients hospitalised during the study period. The mortality rate and mean hospital stays were significantly higher in the study group, and infectious diseases were the most common diagnoses, affecting 389 patients (89.4%), particularly pneumonia (47.1%). Higher CRP was correlated with low albumin levels (p < 0.01). Bacteraemia was the most prevalent diagnosis (38%) in the 84 oncology patients, with a crude mortality rate of 17.6%. CONCLUSION: Infectious diseases, mainly bacterial, were the most common diagnoses in previously healthy children with CRP ≥ 30 mg/dL. Extremely elevated CRP levels were associated with an unfavourable clinical outcome, including high mortality, particularly in oncology patients. Paediatricians should be aware of the significance of extremely elevated CRP levels.

Medical And Surgical Management Of Orbital Cellulitis In Children.

OBJECTIVE: The purpose of this study was to identify features of orbital cellulitis that predict response to conservative treatment without surgical intervention and factors associated with a decision for surgery. PATIENTS AND METHODS: The medical files of patients diagnosed with orbital cellulitis at a tertiary medical center in central Israel between 1995 and 2010 were reviewed for clinical data, diagnosis, complications, and type of treatment. Comparison was made between patients treated with antibiotics and patients treated with antibiotics and surgery. RESULTS: Fifty-one patients (35 male) with a mean age of 6.1 years were identified. Main clinical signs included fever (mean 38.5°C), proptosis (82.3%), extraocular motility restriction (74.5%), and ocular pain (41.1%). Forty-one patients were successfully treated with antibiotics and 10 required endoscopic sinus surgery. On between-group comparison, the surgery group had severe eye pain (p = 0.009), severe proptosis (P = 0.02), longer intravenous antibiotic treatment (13.2 vs. 9.2 days, p = 0.04), and several imaging findings. Additional factors associated with surgical intervention included older children, subperiorbital abscess, larger dimension of the abscess (mean 15 mm), involvement of frontal sinuses and findings of intraorbital air bubbles. There was no visual deterioration in either group and no late sequelae. CONCLUSION: Factors associated with surgery included age older than 9 years, severe ocular pain, severe proptosis, and subperiorbital large abscess. These may be used for early identification of patients at risk of failure of only medical management.

C-Reactive protein levels in children with primary herpetic gingivostomatitis.

BACKGROUND: C-reactive protein (CRP) is often used to distinguish bacterial from viral infections. However, the CRP level does have implications, which depend on the clinical scenario and are still under research. OBJECTIVES: To evaluate the distribution of CRP levels in children with primary herpetic gingivostomatitis. METHODS: The electronic database of a tertiary pediatric medical center was searched for all inpatients with a diagnosis of primary herpetic gingivostomatitis without bacterial coinfection. Background and clinical information was collected and CRP levels were analyzed. RESULTS: The study group consisted of 66 patients aged 8 months to 7.1 years who met the study criteria. The average CRP was 7.4 mg/dl (normal 0.5 mg/dl). More than a third of the patients had a level higher than 7 mg/dl. CONCLUSIONS: High values of CRP are prevalent in patients with primary herpetic gingivostomatitis, similar to adenoviral infections and some bacterial infections.

Role of C-reactive protein velocity in the diagnosis of early bacterial infections in children after cardiac surgery.

Fever after cardiac surgery in children may be due to bacterial infection or noninfectious origin like systemic inflammatory response syndrome (SIRS) secondary to bypass procedure. A marker to distinguish bacterial from nonbacterial fever in these conditions is clinically important. The purpose of our study was to evaluate, in the early postcardiac surgery period, whether serial measurement of C-reactive protein (CRP) and its change over time (CRP velocity) can assist in detecting bacterial infection. A series of consecutive children who underwent cardiac surgery with bypass were tested for serum levels of CRP at several points up to 5 days postoperatively and during febrile episodes (>38.0°C). Findings were compared among febrile patients with proven bacterial infection (FWI group; sepsis, pneumonia, urinary tract infection, deep wound infection), febrile patients without bacterial infection (FNI group), and patients without fever (NF group). In all, 121 children were enrolled in the study, 31 in the FWI group, 42 in the FNI group, and 48 patients in the NF group. Ages ranged from 4 days to 17.8 years (median 19.0, mean 46 ± 56 months). There was no significant difference among the groups in mean CRP level before surgery, 1 hour, and 18 hours after. A highly significant interaction was found in the change in CRP over time by FWI group compared with FNI group (P < .001). Mean CRP velocity ([fCRP - 18hCRP]/[fever time (days) - 0.75 day]) was significantly higher in the infectious group (4.0 ± 4.2 mg/dL per d) than in the fever-only group (0.60 ± 1.6 mg/dL per d; P < .001). A CRP velocity of 4 mg/dL per d had a positive predictive value (PPV) of 85.7% for bacterial infection with 95.2% specificity. Serial measurements of CRP/CRP velocity after cardiac surgery in children may assist clinicians in differentiating postoperative fever due to bacterial infection from fever due to noninfectious origin.

Procalcitonin level as an aid for the diagnosis of bacterial infections following pediatric cardiac surgery.

PURPOSE: The aim of the present study was to determine if blood procalcitonin can serve as an aid to differentiate between bacterial and nonbacterial cause of fever in children after cardiac surgery. MATERIALS AND METHODS: A nested case-control study of children who underwent open cardiac surgery in critical care units of fourth-level pediatric hospital was performed. Blood samples for procalcitonin level were collected 1 day before operation; 1 hour postoperation; on postoperative days 1, 2, and 5; and on the day of fever, when it occurred. RESULTS: Of 665 children who underwent cardiac bypass surgery, 126 had a febrile episode postoperatively, 47 children with a proven bacterial infection and 79 without bacterial infection. Among the 68 children in whom fever developed within the first 5 postoperative days, procalcitonin level at fever day was significantly higher in those with bacterial infection (n = 16) than in those without infection (n = 52). Similarly, among the 58 children in whom fever developed after day 5 postoperation, a significant difference was found in procalcitonin level at fever day between those with (n = 31) and without (n = 27) bacterial infection. CONCLUSION: During the critical early and late periods after cardiac surgery in children, procalcitonin level may help to differentiate patients with bacterial infection from patients in whom the fever is secondary to nonbacterial infectious causes.

Prolonged course of familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis is usually diagnosed in the first 2 years of life and, if untreated, is rapidly fatal. We describe a 10-year-old boy with a 9-year history of prolonged fever and progressive hepatosplenomegaly who was diagnosed as having hemophagocytic lymphohistiocytosis 2, being homozygote to a previously described mutation in the PRF1 gene, and cured by the HLH-2004 protocol and allogenic bone marrow transplantation. This unique case emphasizes the heterogeneity of this disease and the diversity of its clinical presentations.

Ecthyma gangrenosum caused by disseminated Exserohilum in a child with leukemia: a case report and review of the literature.

We report an 8-year-old boy with acute leukemia who developed ecthyma gangrenosum secondary to infection with Exserohilum spp., a rare cause of human disease. The skin, paranasal sinuses and lungs were involved. To the best of our knowledge, this is the first report of ecthyma gangrenosum caused by Exserohilum spp. This case emphasizes the importance of prompt skin biopsy for early diagnosis and treatment of this life-threatening infection.