Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

BACKGROUND: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

High frequency of multidrug-resistant gram-negative rods in 2 neonatal intensive care units in the Philippines.

BACKGROUND: Although hospital-acquired infections appear to be a growing threat to the survival of newborns in the developing world, the epidemiology of this problem remains poorly characterized. METHODS: During a 10-month period, we conducted prospective longitudinal surveillance for colonization and bloodstream infection caused by gram-negative rods among all infants hospitalized in the 2 largest neonatal intensive care units in Manila, the Philippines. We determined antibiotic susceptibilities and calculated adjusted odds ratios for risk factors for bacteremia by means of multivariate logistic regression. RESULTS: Of 1,831 neonates enrolled during a 10-month period, 1,017 (55.5%) became newly colonized and 358 (19.6%) became bacteremic with a drug-resistant gram-negative rod, most commonly Klebsiella species, Enterobacter species, Acinetobacter species, and Pseudomonas aeruginosa. Of the invasive isolates, 20% were resistant to imipenem, 41% to trimethoprim-sulfamethoxazole, 52% to amikacin, 63% to ampicillin-sulbactam, 67% to ceftazidime, and 80% to tobramycin. The factors significantly associated with an increased risk of bacteremia were mechanical ventilation and prematurity. Additionally, colonization with a drug-resistant gram-negative rod was an independent risk factor for bacteremia (odds ratio, 1.4 [95% confidence interval, 1.0-1.9]). CONCLUSIONS: Colonization with a drug-resistant gram-negative rod was an independent risk factor for sepsis. If our data are typical, the unusually high intensity of colonization pressure and disease caused by multidrug-resistant gram-negative rods at these 2 neonatal intensive care units indicates an emerging healthcare crisis in the developing world. Improved infection control methods are therefore critically needed in developing countries.