Multidrug-resistant tuberculosis in children: A practical update on epidemiology, diagnosis, treatment and prevention.

Pediatric multidrug-resistant tuberculosis (MDR-TB) remains a significant global problem, and there are numerous barriers preventing children with MDR-TB from being identified, confirmed with microbiologic tests, and treated with a safe, practical, and effective regimen. However, several recent advances in diagnostics and treatment regimens have the promise to improve outcomes for children with MDR-TB. We introduce this review with two cases that exemplify both the challenges in management of MDR-TB in children, but also the potential to achieve a positive outcome. More than 30,000 cases of MDR-TB per year are believed to occur in children but less than 5% are confirmed microbiologically, contributing to poorer outcomes and excess mortality. Rapid molecular-based testing that provides information on rifampin susceptibility is increasingly globally available and recommended for all children suspected of TB disease--but remains limited by challenges obtaining appropriate samples and the paucibacillary nature of most pediatric TB. More complex assays allowing better characterization of drug-resistant isolates are emerging. For children diagnosed with MDR-TB, treatment regimens have traditionally been long and utilize multiple drugs associated with significant side effects, particularly injectable agents. Several new or repurposed drugs including bedaquiline, delamanid, clofazimine and linezolid now allow most treatment regimens to be shorter and all-oral. Yet data to support short, all-oral, novel regimens for young children containing pretomanid remain insufficient at present, and there is a compelling need to conduct pediatric trials of promising therapeutics and MDR-TB treatment regimens.

First-Generation Cephalosporins for Treatment of Acute Hematogenous Osteomyelitis in Children: A Study of Efficacy and Adverse Effects.

Background: Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As Staphylococcus aureus is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule. Methods: We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy. Results: There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis. Conclusions: Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible S aureus or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.

Pediatric Utilization of Methicillin-resistant Staphylococcus aureus Nasal Swabs for Antimicrobial Stewardship.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) can cause serious infections and empiric treatment regimens in children frequently include an anti-MRSA antibiotic. Studies in adults have demonstrated a high negative predictive value (NPV) of MRSA nasal swabs (MNS) in a variety of infectious syndromes. Negative MNS have been utilized as a tool to guide de-escalation of anti-MRSA antibiotics in adults, especially in those with lower respiratory tract infections, but data in children is minimal. The primary objective of this study was to determine the NPV and positive predictive value (PPV) of MNS in children hospitalized for treatment of an infection. METHODS: This was a single-site, retrospective cohort study of pediatric patients admitted with a suspected infectious diagnosis who had an MNS performed during their hospitalization between June 1, 2018 and November 25, 2022. RESULTS: This study identified 172 patients who met the inclusion criteria. Eleven (6.4%) nasal swabs were positive for MRSA and 10 (5.8%) microbiological cultures from suspected sources of infection were identified to be positive for MRSA. The MNS was found to have a sensitivity of 20%, specificity of 94%, PPV of 18% and NPV of 95% for all sites of infection. CONCLUSION: MNS has a high NPV and low PPV in children. MNS can be utilized as an antimicrobial stewardship tool to guide the safe de-escalation of anti-MRSA antibiotics in children.

Letermovir as Cytomegalovirus Prophylaxis in a Pediatric Cohort: A Retrospective Analysis.

Letermovir is an attractive cytomegalovirus (CMV) prophylactic agent, but published data in children are scarce. This retrospective chart review aimed to describe our experience using letermovir as CMV prophylaxis in pediatric hematopoietic cell transplantation (HCT) recipients. Pediatric patients (age <20 years) undergoing allogeneic HCT and receiving letermovir prophylaxis in the Mayo Clinic Pediatric Bone Marrow Transplant Program were eligible for inclusion in this retrospective chart review. Medical records were reviewed to evaluate letermovir dosing, CMV levels, laboratory values, and reports of adverse effects. Between October 2020 and April 2022, 9 patients age 4 to 19 years undergoing allogeneic HCT in the Pediatric Bone Marrow Transplant Program received letermovir prophylaxis, either 240 mg or 480 mg daily at a mean and median dose of 10 mg/kg/day. Letermovir was crushed and administered via nasogastric tube in 4 of 9 patients. Two patients received letermovir for secondary CMV prophylaxis after initial treatment with ganciclovir/valganciclovir, and the remaining 7 received letermovir for primary prophylaxis. One patient, a 20-kg 6-year-old female receiving 240 mg (12 mg/kg), experienced low-level CMV viremia while on letermovir. No other patients experienced CMV reactivation while on letermovir prophylaxis. In 2 patients, transient mild transaminitis was noted within the first weeks of letermovir therapy, which resolved without intervention, and its relationship to letermovir could not be clearly established. Letermovir administration was feasible and well tolerated as CMV prophylaxis in our small cohort of pediatric patients undergoing HCT. Larger, prospective studies are warranted to confirm the safety and efficacy of letermovir in children. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

A Quality Improvement Project Aimed at Standardizing the Prescribing of Fluconazole Prophylaxis in a Level IV Neonatal Intensive Care Unit.

Introduction: Invasive candidiasis has a high morbidity and mortality among premature neonates. Antifungal prophylaxis with fluconazole significantly lowers the risk of invasive fungal infection in this population. We noted the use of fluconazole prophylaxis in our level IV neonatal intensive care unit (NICU) was variable and sought to standardize prescribing of prophylactic fluconazole. Methods: We formed a multidisciplinary team to develop an evidence-based protocol using literature and expert consensus to guide appropriate use of fluconazole prophylaxis in our level IV NICU. After determining baseline fluconazole prophylaxis prescribing before protocol implementation, we used plan-do-study-act (PDSA) cycles to introduce protocolized prescribing and incorporate it into daily practice. A 6-month intervention phase was followed by a 2-year control phase, in which monthly audits were performed to evaluate protocol adherence. Results were displayed in a statistical process control chart. Results: Before protocol implementation, fluconazole prophylaxis prescribing adhered to the protocol in 81% of patients. During the first PDSA cycle, adherence increased significantly to 94.5% (86/91 patients), which further increased to 98.7% (74/75 patients) during the second PDSA cycle and remained at 96% (120/125 patients) during the control phase (P < 0.0001). Conclusions: A multidisciplinary group-designed protocol was successful in standardizing fluconazole prophylaxis prescribing for infants in the level IV NICU. Adherence to protocol was high following implementation and was sustained for the duration of the project. There were no cases of invasive candidiasis noted.

Assessing Pediatric Feeding Disorders by Domain in Complex Aerodigestive Patients.

OBJECTIVE: Pediatric feeding disorder (PFD) is defined as impaired oral intake, associated with dysfunction in at least one of four domains: medical, nutritional, feeding skill, and/or psychosocial. The pediatric aerodigestive patient presents with conditions impacting airway, breathing, feeding, swallowing, or growth. The objective of the study was to determine the prevalence of PFD and dysfunctional domain, in the aerodigestive patient presenting to a tertiary aerodigestive clinic. METHODS:  Twenty-five charts from patients enrolled in Mayo Clinic Children's Center Aerodigestive Program were retrospectively reviewed for documentation of dysfunction within the four feeding disorder domains. Results from the aerodigestive triple scope, functional endoscopic evaluation of swallow (FEES), and videofluoroscopic swallow study (VFSS) were recorded. Height and weight z-scores were compared between the initial assessment and 6-12 months later. RESULTS: Median age was 20 months (range 2-81 months). Of the patients, 100% (n = 25) had dysfunction in at least one PFD domain. The domain identified most frequently was medical dysfunction (96%; n = 24). Feeding dysfunction was observed in 76% (n = 19). Psychosocial dysfunction was observed in 76% (n = 19). Nutritional dysfunction was observed in 60% (n = 15). Dysfunction in three or greater domains was seen in 80% (n = 20). Weight z-score increased in 76% (n = 19) of patients 6 to 12 months after the initial aerodigestive evaluation. CONCLUSION:  Aerodigestive patients frequently have PFD and utilizing the consensus definition of PFD at intake may enhance clinical assessment and therapeutic evaluation, and provide a framework to measure outcomes in this heterogeneous patient population.