Frosted Branch Angiitis Associated With Cytomegalovirus in a Pediatric Autologous Stem Cell Transplant Patient: Case Report and Review of the Literature.

BACKGROUND: Frosted branch angiitis (FBA) is a rare phenomenon of panuveitis which may occur secondary to cytomegalovirus (CMV) causing acute visual disturbances. CMV infection is a known complication in allogenic stem cell transplant (SCT) patients but is uncommon following autologous SCT. OBSERVATION: We describe a 17-month-old medulloblastoma patient with sudden onset visual impairment following second autologous SCT. The patient was CMV seropositive, polymerase chain reaction negative before second SCT. At the time of presentation with visual complaints, the patient was diagnosed with FBA associated with CMV reactivation. Treatment included antivirals and immunosuppressive medication with visual recovery. CONCLUSION: FBA induced by CMV should be considered as a differential diagnosis in pediatric patients undergoing autologous bone marrow transplant with rapidly progressive visual impairment.

Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial.

Importance: Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required. Objective: To determine whether 5 days of high-dose amoxicillin for CAP was associated with noninferior rates of clinical cure compared with 10 days of high-dose amoxicillin. Design, Setting, and Participants: The SAFER (Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections) study was a 2-center, parallel-group, noninferiority randomized clinical trial consisting of a single-center pilot study from December 1, 2012, to March 31, 2014, and the follow-up main study from August 1, 2016, to December 31, 2019 at the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. Research staff, participants, and outcome assessors were blinded to treatment allocation. Eligible children were aged 6 months to 10 years and had fever within 48 hours, respiratory symptoms, chest radiography findings consistent with pneumonia as per the emergency department physician, and a primary diagnosis of pneumonia. Children were excluded if they required hospitalization, had comorbidities that would predispose them to severe disease and/or pneumonia of unusual origin, or had previous ß-lactam antibiotic therapy. Data were analyzed from March 1 to July 8, 2020. Interventions: Five days of high-dose amoxicillin therapy followed by 5 days of placebo (intervention group) vs 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin (control group). Main Outcomes and Measures: Clinical cure at 14 to 21 days. Results: Among the 281 participants, the median age was 2.6 (interquartile range, 1.6-4.9) years (160 boys [57.7%] of 279 with sex listed). Clinical cure was observed in 101 of 114 children (88.6%) in the intervention group and in 99 of 109 (90.8%) in the control group in per-protocol analysis (risk difference, -0.016; 97.5% confidence limit, -0.087). Clinical cure at 14 to 21 days was observed in 108 of 126 (85.7%) in the intervention group and in 106 of 126 (84.1%) in the control group in the intention-to-treat analysis (risk difference, 0.023; 97.5% confidence limit, -0.061). Conclusions and Relevance: Short-course antibiotic therapy appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should consider recommending 5 days of amoxicillin for pediatric pneumonia management in accordance with antimicrobial stewardship principles. Trial Registration: ClinicalTrials.gov Identifier: NCT02380352.

Short-course antimicrobial therapy for paediatric respiratory infections (SAFER): study protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is commonly diagnosed in children. The Infectious Disease Society of America guidelines recommend 10 days of high-dose amoxicillin for the treatment of non-severe CAP but 5-day "short course" therapy may be just as effective. Randomized trials in adults have already demonstrated non-inferiority of 5-day short-course treatment for adults hospitalized with severe CAP and for adults with mild CAP treated as outpatients. Minimizing exposure to antimicrobials is desirable to avoid harms including diarrhoea, rashes, severe allergic reactions, increased circulating antimicrobial resistance, and microbiome disruption. METHODS: The objective of this multicentre, randomized, non-inferiority, controlled trial is to investigate whether 5 days of high-dose amoxicillin is associated with lower rates of clinical cure 14-21 days later as compared to 10 days of high-dose amoxicillin, the reference standard. Recruitment and enrolment will occur in the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. All children in the study will receive 5 days of amoxicillin after which point they will receive either 5 days of a different formulation of amoxicillin or a placebo. Assuming a clinical failure rate of 5% in the reference arm, a non-inferiority margin of 7.5%, one-sided alpha set at 0.025 and power of 0.80, 270 participants will be required. Participants from a previous feasibility study (n = 60) will be rolled over into the current study. We will be performing multiplex respiratory virus molecular testing, quantification of nasopharyngeal pneumococcal genomic loads, salivary inflammatory marker testing, and faecal microbiome profiling on participants. DISCUSSION: This is a pragmatic study seeking to provide high-quality evidence for front-line physicians evaluating children presenting with mild CAP in North American emergency departments in the post-13-valent pneumococcal, conjugate vaccine era. High-quality evidence supporting the non-inferiority of short-course therapy for non-severe paediatric CAP should be generated prior to making changes to established guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02380352 . Registered on 2 March 2015.

To anticoagulate? Controversy in the management of thrombotic complications of head & neck infections.

OBJECTIVE: To review the thrombotic complications of head and neck infections, including Lemierre's syndrome, and their management. METHODS: A retrospective review of pediatric patients presenting to McMaster Children's Hospital from 2009 to 2013 was undertaken. The literature was reviewed for evidence regarding the use of anticoagulation therapy in this population. RESULTS: Eleven cases (6 males, 5 females) were identified. The median age was 10.9 (range 14 months-17 years). The most frequent head and neck infection causing a thrombotic complication was mastoiditis (n = 6). All had thrombi identified on imaging, with the most common location being the sigmoid sinus (n = 6) followed by the internal jugular vein (n = 5). All 11 patients were anti-coagulated with low molecular weight heparin (LMWH) within a median of 2 days of diagnosis (average duration 105.8 days). Ten patients (90.9%) had thrombus improvement or resolution within a median of 3.4 months (range 1.0-13.9). Adverse sequelae from the thrombi were MCA infarct (n = 1), septic pulmonary emboli (n = 4), cranial nerve palsies (n = 3) and Horner's syndrome (n = 2). There were no adverse effects from anti-coagulation therapy. Review of the literature revealed anticoagulant use in 63.7% of pediatric cases reported since 2002. CONCLUSION: Anticoagulation remains controversial in the management of thrombotic complications from head and neck infections. Based on this case series, certain recommendations can be made regarding the benefits of anticoagulation, which appear to outweigh the risks. Further research is required to establish evidence for consensus in the antithrombotic management of thrombotic sequelae of head and neck infections.

Pyomyositis Causing Temporary Quadriparesis During Induction Therapy for Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

Pyomyositis (PM) is a purulent infection of skeletal muscle. It is often associated with immunosuppression in temperate climates. Herein, we report a case of PM causing temporary quadriparesis in a 14-year-old girl undergoing induction therapy for acute lymphoblastic leukemia and we review the reported pediatric cases associated with induction therapy for hematologic malignancies. Early symptoms of PM can be mistaken for the side effects of chemotherapeutic agents. Greater awareness of the clinical picture of PM will aid in early diagnosis and treatment. With appropriate medical therapy and timely abscess drainage, morbidity and mortality is greatly reduced.

Severe late-onset multisystem cytomegalovirus infection in a premature neonate previously treated for congenital infection.

BACKGROUND: Cytomegalovirus is the most common pathogen causing congenital infection and can result in significant neurodevelopmental adverse outcomes. For this reason, it is the standard of care in many regions to treat congenital cytomegalovirus infection involving the brain with six weeks of ganciclovir. There have been no reports in the published literature of significant cytomegalovirus neonatal infection in infants previously treated for congenital infection. CASE PRESENTATION: A preterm male infant with congenital symptomatic cytomegalovirus infection was initially treated with over 8 weeks of ganciclovir between the ages of 3 and 14 weeks. At four months chronologic age, just prior to planned discharge, he developed an episode of life-threatening multisystem cytomegalovirus disease notable for severe pneumonitis, encephalitis, hepatitis, and disseminated intravascular coagulation. This disease resolved after re-treatment with a prolonged course of intravenous ganciclovir and oral valganciclovir. CONCLUSIONS: Clinicians should be aware of the possibility of recurrence of congenital cytomegalovirus infection, especially in preterm infants. Serial plasma cytomegalovirus viral load monitoring may have a role in the management of premature infants treated with ganciclovir; had the diagnosis of recrudescent cytomegalovirus infection been considered sooner, specific therapy might have been more quickly initiated and perhaps further morbidity would have been prevented.

A pilot study on cost-related medication nonadherence in Ontario.

BACKGROUND: Cost-related nonadherence (CRN) describes patients cutting back on their prescribed medication due to an inability to pay. CRN is influenced by drug insurance coverage plans, which vary widely among different healthcare systems. Little is known about CRN in Canada and Ontario. OBJECTIVE: To develop and pilot a questionnaire about CRN. METHODS: An interviewer-administered questionnaire assessing demographics, socioeconomic status, health status and health literacy, medication costs and CRN was developed for this pilot study. Participants were recruited from a general internal medicine rapid assessment outpatient clinic of a large urban teaching hospital. RESULTS: Sixty patients were recruited (mean age 60.3 years; 48.3% female; mean of 5.3 prescription medications per patient). Nine patients (15%) reported some form of CRN. Unfilled prescriptions, delayed prescriptions, less frequent and smaller doses were the most common forms of CRN. Seven patients (11.7%) had no drug insurance. Patients without drug insurance were more likely to experience CRN than patients with private insurance (OR 20.70, 95% CI 1.46-292.75); government coverage also increased the likelihood of CRN compared to private coverage (OR 4.51, 95% CI 0.376-54.11). Patients spending over $100 a month out-of-pocket were more likely to experience CRN than patients spending less than $20 (OR 42.52, 95% CI 2.02-894.03). Thirty-three patients (55%) said that their physicians had not asked them about how they deal with the cost of prescriptions. CONCLUSION: Based on our pilot survey, a significant minority of specialty clinic outpatients experience CRN and prescribers frequently forget to inquire whether patients can afford their medications.

Horizontal transmission of group B streptococcus in a neonatal intensive care unit.

The incidence of early-onset group B streptococcal (GBS) sepsis in the neonatal population has decreased substantially since the introduction of maternal intrapartum antibiotic prophylaxis and routine prenatal screening. However, these strategies have not reduced the incidence of late-onset GBS infections. Additional research pertaining to the transmission of late-onset GBS infections is required to develop effective preventive methods. The present report describes probable horizontal transmission of late-onset GBS infection among three infants in a neonatal intensive care unit. GBS strain confirmation was based on the microbiological picture, antibiogram and pulsed-field gel electrophoresis. These cases highlight the morbidity associated with late-onset GBS disease and the importance of considering horizontal transmission as an etiological factor in GBS infection in the newborn period. Further studies assessing horizontal transmission in late-onset GBS disease may improve prevention and early intervention.

Health Risks Associated with Visiting Friends and Relatives in Developing Countries.

An increasingly large proportion of immigrants to developed countries is arriving from less developed countries in Africa, Asia, and Latin America. When these immigrants return to their country of origin to visit friends and relatives, they are at high risk of acquiring tropical infections, compared with other travelers. Immigrants who return to their country of origin to visit friends and relatives (VFRs) are more likely to travel to rural areas for long periods of time, to consume contaminated food and beverages, and to have more prolonged, intimate contact with local populations. As a group, they are less likely to seek pretravel advice or take antimalarial chemoprophylaxis. This article discusses the increased risk of tuberculosis, malaria, food- and waterborne illnesses, hepatitis A, and HIV and other sexually transmitted infections in VFRs.