Peter Paul C. Lim

Background: The development of broad-range polymerase chain reaction (BR-PCR) and next-generation sequencing techniques has significant implications for antimicrobial stewardship by increasing clinicians’ ability to provide a tailored antimicrobial regimen. We sought to explore the clinical utility of BR-PCR testing and its impact on antimicrobial treatment among an adult cohort in a large hospital system. Methods: We retrospectively evaluated samples that underwent BR-PCR testing between 2017 and 2021 and summarized their clinical characteristics and impact on antimicrobial therapy. We identified BR-PCR testing as having clinical utility if the results led to adjustment of antimicrobial choice or duration or to confirmation of the initial empiric regimen, while no clinical utility was assigned to results that were negative or clinically insignificant, unavailable due to loss to follow-up, or lacking clinical indication (treatment completed before the test results returned or conventional cultures revealed the causative pathogen). Results: Among 359 specimens, BR-PCR was positive for 107 (30%). Clinical utility was identified for 106 (29.5%) specimens, including 45 with negative BR-PCR results. The rates of clinical utility varied based on the type of sample tested, with the highest clinical utility associated with cranial samples (60%), followed by body fluid (56%) and endovascular (54%) samples, and the lowest with CSF (15%) and bone and joint (19%) samples. We also identified many BR-PCR tests that were not clinically indicated (23.4%). Conclusions: This study highlights the utility of BR-PCR testing to support antimicrobial stewardship initiatives. Further studies are needed to identify clinical scenarios in which it is appropriate to order BR-PCR testing and for a careful interpretation of negative BR-PCR results.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical trials.gov identifier: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical Trials.gov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011

Pseudomembranous conjunctivitis, caused by inflammation of the conjunctiva, is characterized by conjunctival injection, mucopurulent discharge, and formation of a thin membrane overlying the conjunctiva. This is often caused by a viral or bacterial infection. This case report discusses pseudomembranous conjunctivitis from Escherichia coli in a newborn infant which, to our knowledge, has not been reported in relevant literature. This infection was likely transmitted perinatally given that the mother of the infant had blood cultures growing E. coli with the same susceptibilities as the newborn. In addition, we discuss relevant literature on the subject including etiologies, management, and complications of pseudomembranous conjunctivitis.

Sepsis remains the leading cause of childhood mortality worldwide. The evolving definition of pediatric sepsis is extrapolated from adult studies. Although lacking formal validation in the pediatric population, this working definition has historically proven its clinical utility. Prompt identification of pediatric sepsis is challenging as clinical picture is often variable. Timely intervention is crucial for optimal outcome, thus biomarkers are utilized to aid in immediate, yet judicious, diagnosis of sepsis. Over time, their use in sepsis has expanded with discovery of newer biomarkers that include genomic bio-signatures. Despite recent scientific advances, there is no biomarker that can accurately diagnose sepsis. Furthermore, older biomarkers are readily available in most institutions while newer biomarkers are not. Hence, the latter’s clinical value in pediatric sepsis remains theoretical. Albeit promising, scarce data on newer biomarkers have been extracted from research settings making their clinical value unclear. As interest in newer biomarkers continue to proliferate despite their ambiguous clinical use, the literature on older biomarkers in clinical settings continue to diminish. Thus, revisiting the evolving value of these earliest biomarkers in optimizing pediatric sepsis diagnosis is warranted. This review focuses on the four most readily available biomarkers to bedside clinicians in diagnosing pediatric sepsis. Impact The definition of pediatric sepsis remains an extrapolation from adult studies. Older biomarkers that include C-reactive protein, procalcitonin, ferritin, and lactate are the most readily available biomarkers in most pediatric institutions to aid in the diagnosis of pediatric sepsis. Older biomarkers, although in varying levels of reliability, remain to be useful clinical adjuncts in the diagnosis of pediatric sepsis if used in the appropriate clinical context. C-reactive protein and procalcitonin are more sensitive and specific among these older biomarkers in diagnosing pediatric sepsis although evidence varies in different age groups and clinical scenarios.

The use of 16S rRNA sequencing in culture-negative infections has improved identification of bacterial pathogens in select scenarios, but its clinical impact requires further elucidation, especially in the pediatric population. This retrospective study aims to determine the clinical utility of 16S rRNA sequencing on the clinical management of pediatric culture-negative infections in our institution. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (p < 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (n = 9, 30%), followed equally by joint fluid (n = 6, 20%) and bone (n = 6, 20%), with no difference between fluid and fresh tissue specimens (p = 0.346). Although the difference was not statistically significant (p = 0.4111), the overall use of broad-spectrum coverage was decreased. The median number of antibiotics was decreased from two to one (p < 0.0001) based on 16S rRNA sequencing results. The results suggest that 16S rRNA sequencing has a significant impact on decreasing the number of antibiotics used in the treatment of pediatric culture-negative infections. 16S rRNA sequencing performed on pulmonary specimens has the highest likelihood of identifying a pathogen compared to other specimen types. Additional cost–benefit analysis needs to be completed to further determine clinical benefit.

Isotretinoin or 13-cis-retinoic acid, a derivative of vitamin A, is a highly effective therapy for severe and resistant acne. Its usage is restricted worldwide because of its teratogenic potential. The most common side effects are dermatologic, cheilitis, increased skin fragility, and susceptibility to sunburns. Rare side effects include myalgias and arthralgias. It also causes transient laboratory abnormalities such as elevated creatine kinase (CK). Very few cases of isotretinoin-induced severe muscle injury leading to rhabdomyolysis have been reported in the literature. We report a 15-year-old adolescent who developed rhabdomyolysis after a bout of vigorous exercising while on long-term isotretinoin therapy.