Nirsevimab: Alleviating the burden of RSV morbidity in young children.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections (LRTIs) and hospital admissions in early childhood. Recent advancements in novel preventive therapies, including extended half-life monoclonal antibodies and antenatal vaccination, have afforded new opportunities to significantly reduce the burden of this infection. Nirsevimab is a novel monoclonal antibody that provides sustained protection against RSV for at least 5 months among newborns and young children. It has received regulatory approval in numerous countries and is being implemented across various settings. Two pivotal Phase 3 trials (MELODY, HARMONIE) demonstrated significant reductions in RSV-associated LRTI hospitalisations following nirsevimab administration, with treatment efficacy of 62.1% and 83.2%. Emerging real-world data from early adopters of nirsevimab corroborates these findings. Studies from Spain, Luxembourg, France and the USA report effectiveness rates between 82% and 90% in preventing RSV-associated hospitalisations among infants entering their first RSV season. Current implementation strategies for nirsevimab have primarily focused on seasonal administration for all infants, aligned to local RSV seasons, and often include catch-up doses for those born before the season begins. Available cost-effectiveness analyses indicate that while nirsevimab offers significant potential public health benefits, its adoption must carefully consider economic factors such as treatment costs, implementation strategies tailored to local viral epidemiology, and logistics for vaccine delivery. Overall, nirsevimab presents a promising opportunity to alleviate the burden of severe RSV infections in young children. However, ongoing surveillance and refinements in implementation strategies are crucial to optimise its impact and ensure sustainability across diverse health-care settings.

Complements and Their Role in Systemic Disorders.

The complement system is critical to the body's innate defense against exogenous pathogens and clearance of endogenous waste, comprising the classical, alternative, and lectin pathways. Although tightly regulated, various congenital and acquired diseases can perturb the complement system, resulting in specific complement deficiencies. Systemic rheumatic, neurological, ophthalmological, renal, and hematological disorders are some prototypical complement-mediated diseases. An adequate understanding of the mechanisms of the normal complement system and the pathophysiology of complement dysregulation is critical for providing diagnostic clues and appropriately managing these conditions. This review guides clinicians in understanding the role of complement factors in systemic diseases and what diagnostic and therapeutic options are available for complement-mediated disorders.

Burden of antibiotic resistance in infections among very-low-birthweight infants in Singapore.

Introduction: Recent reports have described the increasing predominance of Gram-negative organisms among invasive bacterial infections affecting preterm infants. This changing pattern of infections is concerning due to the spread of antibiotic resistance among Gram-negatives. Method: We conducted a single-centre, retrospective cohort study involving very-low-birthweight (VLBW) (<1500 grams) infants born <32 weeks gestation, with culture-proven infections (blood, urine, cerebrospinal fluid [CSF]) in the neonatal intensive care unit from 1 January 2005 to 31 October 2017. Results: A total of 278 out of 2431 (11.4%) VLBW infants born <32 weeks gestation developed 334 infections, i.e. 52 (15.6%) early-onset infections (EOIs) and 282 (84.4%) late-onset infections (LOIs). The overall incidence decreased from 247 to 68 infections per 1000 infants over the study period, corresponding to reductions in LOI (211 to 62 infections per 1000 infants). A total of 378 bacteria were isolated, i.e. Gram-negatives accounted for 70.9% (45 of 59 [76.3%] EOI; 223 of 319 [69.9%] LOI). Specific resistant organisms were noted, i.e. Methicillin-resistant Staphylococcus aureus (8 of 21 S. aureus infections [38.1%]); Cephalosporin-resistant Klebsiella (18 of 62 isolates [29.0%]) and multidrug-resistant [MDR] Acinetobacter (10 of 27 isolates [37.0%]). MDR organisms accounted for 85 of 195 (43.6%) Gram-negative infections from the bloodstream and CSF. Based on laboratory susceptibility testing, only 63.5% and 49.3% of infecting bacteria isolated in blood were susceptible to empiric antibiotic regimens used for suspected EOI and LOI, respectively. Conclusion: Gram-negative bacteria are the predominant causative organisms for EOI and LOI and are frequently MDR. Understanding the pattern of antimicrobial resistance is important in providing appropriate empiric coverage for neonatal infections.