Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.

PURPOSE OF REVIEW: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. RECENT FINDINGS: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. SUMMARY: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Pneumatic retinopexy versus scleral buckle for repairing simple rhegmatogenous retinal detachments.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a full-thickness break in the sensory retina, caused by vitreous traction on the retina. While pneumatic retinopexy, scleral buckle, and vitrectomy are the accepted surgical interventions for eyes with RRD, their relative effectiveness has remained controversial.  OBJECTIVES: The objectives of this review were to assess the effectiveness and safety of pneumatic retinopexy versus scleral buckle or pneumatic retinopexy versus a combination treatment of scleral buckle and vitrectomy for people with RRD. The secondary objectives were to summarize any data on economic measures and quality of life. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 January 2015. SELECTION CRITERIA: We included all randomized or quasi-randomized controlled trials comparing the effectiveness of pneumatic retinopexy versus scleral buckle (with or without vitrectomy) for eyes with RRD. DATA COLLECTION AND ANALYSIS: After screening for eligibility, two review authors independently extracted study characteristics, methods, and outcomes. We followed systematic review standards as set forth by The Cochrane Collaboration. MAIN RESULTS: We included two randomized controlled trials (218 eyes of 216 participants) comparing the effectiveness of pneumatic retinopexy versus scleral buckle for eyes with RRD. We identified no studies investigating the comparison of pneumatic retinopexy versus a combination treatment of scleral buckle and vitrectomy. Of the two included studies, one was a small study with 20 participants enrolled in Ireland and followed for an average of 16 months. The second study was larger with 196 participants (198 eyes) enrolled in the United States and followed for at least 6 months. Cautious interpretation of the results is warranted, since we graded the evidence as low to moderate quality due to insufficient reporting of study methods and imprecision and inconsistency among study results.Both studies showed fewer eyes achieving retinal reattachment in the pneumatic retinopexy group compared with the scleral buckle group by six-months follow-up (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.77 to 1.02, 218 eyes); however, we are uncertain as to whether the intervention has an important effect on reattachment because the results are imprecise. Eyes in the pneumatic retinopexy group also were more likely to have had a recurrence of retinal detachment by six-months follow-up (RR 1.80, 95% CI 1.00 to 3.24, 218 eyes); however, we are uncertain as to whether the intervention has an important effect on recurrence because the lower CI equals no difference. Neither study reported mean change in visual acuity, quality of life data, or economic measures. Differences between the pneumatic retinopexy group and scleral buckle group were uncertain due to small numbers of events with respect to operative ocular adverse events (RR 0.67, 95% CI 0.32 to 1.42, 218 eyes), development of cataract (RR 0.92, 95% CI 0.06 to 14.54, 198 eyes), glaucoma (RR 0.31, 95% CI 0.03 to 2.91, 198 eyes), macular pucker (RR 0.74, 95% CI 0.20 to 2.67, 198 eyes), and proliferative vitreoretinopathy (RR 0.94, 95% CI 0.30 to 2.96, 218 eyes). Fewer eyes in the pneumatic retinopexy group compared with the scleral buckle group experienced choroidal detachment (RR 0.17, 95% CI 0.05 to 0.57, 198 eyes) or myopic shift equal to or greater than 1 diopter spherical equivalent (RR 0.04, 95% CI 0.01 to 0.13, 198 eyes). AUTHORS' CONCLUSIONS: The evidence suggests that pneumatic retinopexy may result in lower rates of reattachment and higher rates of recurrence than scleral buckle for eyes with RRD, but does not rule out no difference between procedures. The relative safety of the procedures is uncertain and the relative effects of these procedures in terms of other patient-important outcomes, such as visual acuity and quality of life, is unknown. Due to the limited information available between pneumatic retinopexy and scleral buckle procedures, future research addressing these evidence gaps are warranted.

Challenges in the Diagnosis and Management of Recurrent and Severe Clostridioides difficile Infection in Children.

Children with Clostridioides difficile infection (CDI) can experience recurrent or severe disease. Recurrent CDI occurs in 20%-30% of children with an initial CDI episode. A careful clinical evaluation is important to distinguish recurrent CDI from other disorders that cause recurring gastrointestinal symptoms. Multiple treatment options exist for recurrent CDI, but the optimal therapeutic approach remains undefined. Severe or fulminant CDI can result in poor outcomes and significant morbidity in children. Since there is not a validated definition for severe CDI in children, physicians must use their clinical judgment to identify patients with severe CDI to institute appropriate therapy. In this review, we describe the diagnostic and management challenges in caring for children with recurrent and severe CDI.

A Pediatric Infectious Diseases Perspective of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Novel Coronavirus Disease 2019 (COVID-19) in Children.

Understanding the role that children play in the clinical burden and propagation of severe acute respiratory syndrome coronavirus 2, responsible for coronavirus disease 2019 (COVID-19) infections, is emerging. While the severe manifestations and acute clinical burden of COVID-19 have largely spared children compared with adults, understanding the epidemiology, clinical presentation, diagnostics, management, and prevention opportunities and the social and behavioral impacts on child health is vital. Foremost is clarifying the contribution of asymptomatic and mild infections to transmission within the household and community and the clinical and epidemiologic significance of uncommon severe post-infectious complications. Here, we summarize the current knowledge, identify resources, and outline research opportunities. Pediatric infectious diseases clinicians have a unique opportunity to advocate for the inclusion of children in epidemiological, clinical, treatment, and prevention studies to optimize their care as well as to represent children in the development of guidance and policy during pandemic response.

Hyperammonemic Encephalopathy due to Ureaplasma parvum Infection in an Immunocompromised Child.

Idiopathic hyperammonemia is a rare complication with a high mortality rate that occurs in persons with hematologic malignancies or hematopoietic stem cell or solid organ transplant. Patients present with encephalopathy and hyperammonemia in the absence of liver disease or inborn errors of metabolism. Several etiologies have been proposed, including chemotherapeutic agents, medications, and a catabolic state with an elevated nitrogen load in the setting of acute illness. Recently, cases of hyperammonemia in adult lung transplant recipients have been attributed to infection from Ureaplasma parvum or U urealyticum Herein, we report a 12-year-old girl with acute myeloid leukemia and neutropenic fever who developed acute encephalopathy. Laboratory testing revealed severe hyperammonemia (blood ammonia level >1609 µmol/L) with normal liver function studies. U parvum was detected in blood, urine, and respiratory specimens by polymerase chain reaction testing. After antibiotic therapy directed against U parvum, blood ammonia levels normalized, the infection was eradicated, and the patient recovered. We propose that clinicians should test for invasive infection from Ureaplasma species in immunocompromised children with unexplained hyperammonemia.

Acute hemorrhagic edema of infancy with abdominal pain and elevated transaminases.

Acute hemorrhagic edema of infancy is a rare type of leukocytoclastic vasculitis characterized by a triad of fever, edema, and rosette-shaped purpura, mainly over the face, auricles, and extremities in a nontoxic infant. Visceral involvement is infrequent in acute hemorrhagic edema of infancy. We report a case of acute hemorrhagic edema of infancy with abnormal liver function tests and abdominal pain.

Risk Factors for Surgical Site Infections Following Vertical Expandable Prosthetic Titanium Rib (VEPTR) Surgery in Children.

STUDY DESIGN: Case-control study. OBJECTIVES: To identify risk factors for surgical site infections (SSIs) following vertical expandable prosthetic titanium rib (VEPTR) surgery in children. SUMMARY OF BACKGROUND DATA: VEPTR surgery is a growth-sparing approach for early-onset scoliosis and chest or rib abnormalities. SSIs are an important complication following VEPTR surgery. We aimed to identify modifiable risk factors for SSIs following VEPTR surgery. METHODS: Children who underwent VEPTR surgery at a tertiary-care children's hospital from January 2010 through November 2014 were included. SSIs following VEPTR implant or revision surgeries were identified. For each case patient, three control subjects matched by procedure type were randomly selected among those without infection. Patient and surgery-related risk factors were analyzed using conditional logistic regression. RESULTS: Twenty-six infections occurred in 22 subjects following 326 VEPTR surgeries (SSI rate: 8.0%). The infection rate was greater among implant than revision surgeries (15.5% vs. 4.5%; p<.001). Methicillin-susceptible Staphylococcus aureus was the most common pathogen (50% of infections). On multivariate analysis, VEPTR SSI infections were associated with male gender (OR 3.5, 95% CI 0.9-13.2), assisted feeding (OR 4.5, 95% CI 1.0-20.3), administration of preoperative antibiotics more than 30 minutes before surgery (or >60 minutes for vancomycin) (OR 6.9, 95% CI 1.2-39.0), and an intraoperative temperature less than 35.0°C (OR 4.3, 95% CI 0.8-23.7). CONCLUSIONS: Administration of preoperative antibiotics closer to the time of surgery may reduce the risk of SSI in children undergoing VEPTR surgery. Further study is needed to determine the optimal timing of antibiotic prophylaxis for children undergoing spinal surgery. LEVEL OF EVIDENCE: Level III.

Intraoperative hyphema in Descemet membrane endothelial keratoplasty alone or combined with phacoemulsification.

PURPOSE: To identify whether intraoperative hyphema from the peripheral iridotomy during Descemet membrane endothelial keratoplasty (DMEK) is associated with anticoagulant or antiplatelet use, age, combined phacoemulsification, or adverse outcomes. SETTING: Price Vision Group, Indianapolis, Indiana, USA. DESIGN: Retrospective case series. METHODS: Data were obtained from consecutive DMEK cases with an intraoperative iridotomy from July 2015 through July 2016. Hyphema was classified as negative or positive (small or large). Associations with possible risk factors and with transplant outcomes were assessed. RESULTS: Of 445 cases, 262 (59%) were negative for hyphema and 183 (41%) were positive. The proportion of patients who used preoperative anticoagulant or antiplatelet medication did not differ significantly with the hyphema classification (negative hyphema 42%, small hyphema 34%, large hyphema 46%) (P = .31). Likewise, recipient age was not a risk factor for hyphema (P = .085). Hyphema was more likely in cases combined with phacoemulsification than in single DMEK procedures (relative risk, 1.5 [95% confidence interval, 1.2-1.9]). Hyphema was not associated with postoperative rebubbling rates (negative hyphema 10.5%, small hyphema 10.3%, large hyphema 8.0%) (P = .33), 6-month endothelial cell loss (mean = 29%, P = .19), or 6-month visual acuity (mean = 20/25 Snellen in all hyphema groups, P = .98). CONCLUSIONS: Preoperative anticoagulant or antiplatelet use was not a significant risk factor for hyphema. The risk for hyphema was increased somewhat when DMEK was combined with cataract surgery. Intraoperative hyphema did not significantly affect the rebubbling rate, endothelial cell loss, or visual acuity outcomes.

Recurrent Clostridium difficile Infection in Children: Patient Risk Factors and Markers of Intestinal Inflammation.

BACKGROUND: The management of Clostridium difficile infection (CDI) in children is complicated by recurrence rates of 20%-30%. The identification of risk factors associated with recurrent disease might allow early recognition of those children at highest risk. METHODS: Pediatric patients with CDI were identified through clinical laboratory records at 2 tertiary-care children's hospitals from March 2013 through May 2014. Subjects were enrolled and followed for 60 days to assess for recurrent CDI (rCDI). Blood samples were obtained at enrollment to evaluate host interleukin (IL)-8 polymorphisms and anti-toxin A antibody levels; stool samples were obtained for inflammatory markers (lactoferrin, calprotectin, IL-8) and C. difficile ribotype 027 strain status. Thirty days post enrollment, another serum sample was obtained to compare antibody responses. RESULTS: Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. At enrollment, children with malignancy had significantly lower stool calprotectin, lactoferrin and IL-8 than those without malignancy. There was a trend toward increased stool inflammatory markers in those who later developed rCDI. The IL-8 A/A genotype was not associated with recurrent disease. No patients were found to have ribotype 027 or an antibody increase to toxin A. CONCLUSIONS: The rate of rCDI in our pediatric cohort was 30%. Children with rCDI had a trend toward higher fecal inflammatory markers with the initial infection, and these values were lower in children with malignancy. Fecal lactoferrin, calprotectin and IL-8 should be further studied to determine their value in predicting the risk of rCDI in children.

Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection.

Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI. Here we show that excess dietary zinc (Zn) substantially alters the gut microbiota and, in turn, reduces the minimum amount of antibiotics needed to confer susceptibility to CDI. In mice colonized with C. difficile, excess dietary Zn severely exacerbated C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn-binding S100 protein calprotectin has antimicrobial effects against C. difficile and is an essential component of the innate immune response to CDI. Taken together, these data suggest that nutrient Zn levels have a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile.

Ipilimumab-Associated Retinopathy.

Ipilimumab is a novel immunotherapeutic agent that improves survival in patients diagnosed with metastatic melanoma. With the rising incidence of melanoma, the use of this pharmacologic agent is increasing. However, ipilimumab can be associated with rare but serious systemic adverse events. While the mechanism of these systemic adverse events is immune-related dysfunction, the index case highlights a possible direct ocular adverse event associated with ipilimumab infusion resulting in bilateral serous retinal detachment. Close observation of ocular findings using multimodal imaging analysis can provide insights into possible pathophysiology of the condition and guide further management.

Risk Factors for Community-associated Clostridium difficile-associated Diarrhea in Children.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is increasingly diagnosed in children in community settings. This study aims to assess recent antibiotic use and other risk factors in children with community-associated (CA-) CDAD compared with children with other diarrheal illnesses in a tertiary care setting. METHODS: Children with CA-CDAD evaluated at Texas Children's Hospital (Houston, TX) from January 1, 2012 to June 30, 2013 were identified. Two control subjects with community-associated diarrhea who tested negative for C. difficile were matched to case subjects. Data on demographics, medication exposure and outpatient healthcare encounters were collected from medical records. Multivariate logistic regression was performed to identify predictors of pediatric CA-CDAD. RESULTS: Of 69 CA-CDAD cases, most (62.3%) had an underlying chronic medical condition and 40.6% had antibiotic exposure within 30 days of illness. However, no traditional risk factor for CDAD was identified in 23.2% and 15.9% of CA-CDAD cases within 30 and 90 days of illness onset, respectively. Outpatient healthcare encounters within 30 days were more common among CA-CDAD cases than control subjects (66.7% vs. 48.6%; P = 0.01). In the final multivariate model, CA-CDAD was associated with cephalosporin use within 30 days [odds ratio: 3.32; 95% confidence interval: 1.10-10.01] and the presence of a gastrointestinal feeding device (odds ratio: 2.59; 95% confidence interval: 1.07-6.30). CONCLUSIONS: Recent use of cephalosporins and the presence of gastrointestinal feeding devices are important risk factors for community- associated CDAD in children. Reduction in the use of outpatient antibiotics may decrease the burden of CA-CDAD in children.

A hospital-based study of the clinical characteristics of Clostridium difficile infection in children.

BACKGROUND: Clostridium difficile infection (CDI) is an increasingly important cause of morbidity in hospitalized children. We describe the recent epidemiology of pediatric CDI at a children's hospital, compare community-associated (CA) and hospital-associated (HA) infections and identify risk factors for severe disease. METHODS: Children with CDI at Texas Children's Hospital were identified from February 1, 2011, to October 31, 2011. Severe CDI was defined as the presence of a CDI-related complication or ≥2 clinical features: fever, bloody stools, leukocytosis, hypoalbuminemia or elevated creatinine. Standard epidemiologic definitions were used. RESULTS: One-hundred and nine unique patients 1-21 years of age with CDI were identified throughout the study period. The proportions of CA-CDI (41%) and HA-CDI (46%) were similar, whereas community-onset indeterminate CDI (13%) was less common. Children with malignancy or solid organ transplantation were more likely to have HA-CDI. Conversely, all children with inflammatory bowel disease had CA-CDI. Twenty-three patients (21%) met criteria for severe disease and 8 experienced a CDI-related complication, including 1 death attributable to CDI. On multivariate analysis, the presence of a gastrostomy tube (adjusted odds ratio: 3.09; 95% confidence interval: 1.07-8.94) and having community-onset indeterminate disease (adjusted odds ratio: 4.62; 95% confidence interval: 1.28-16.67) were found to be associated with severe CDI. CONCLUSIONS: A substantial proportion of pediatric CDI is CA and there are clinical differences between children with CA-CDI and HA-CDI. Children with CDI frequently experience severe disease, whereas complications are uncommon. Early identification and treatment of CDI should be pursued in children with gastrostomy tube and recent hospitalization.

Sustained improvement in hand hygiene at a children's hospital.

A quality improvement project was conducted to improve hand hygiene at a children's hospital. Interventions included education, performance feedback, an incentive program, and a marketing campaign. There were 9,322 observations performed over a 5-year period. Hospital-wide adherence increased from 39.9% to 97.9%. Adherence of 95% or greater was sustained for over 3 years.

Clostridium difficile: an emerging pathogen in children.

Clostridium difficile is emerging as an important enteric pathogen in children. Historically considered as an asymptomatic colonizer of the gastrointestinal tract, C. difficile infection (CDI) has not been well-studied in pediatric populations. While asymptomatic carriage remains high among infants, recent epidemiological surveillance has demonstrated a rise in the prevalence of CDI in both healthcare and community settings, particularly in children 1-5 years of age. The pathogenesis of pediatric CDI, including the factors underlying the absence of toxin-mediated effects among colonized infants, remains ill-defined. Studies suggest that traditional adult CDI risk factors such as antibiotic and healthcare exposure may not be as important for children who acquire CDI in the community. As recognition of the significant impact of CDI in children increases, the pressing need for deepening our understanding of this disease and identifying optimal therapeutic and preventative strategies is becoming apparent.