Future Challenges in Pediatric and Neonatal Sepsis: Emerging Pathogens and Antimicrobial Resistance

Abstract

The incidence of severe infections caused by multidrug-resistant (MDR) pathogens is currently rising worldwide, and increasing numbers of neonates and children with serious bloodstream infections due to resistant bacteria are being reported. Severe sepsis and septic shock due to gram-negative bacteria represent a significant cause of morbidity and mortality, and contribute to high health care costs. Antimicrobial resistance among Enterobacteriaceae represents a major problem in both health care-associated and community-acquired infections, with extended-spectrum β-lactamases (ESBLs) and carbapenem-resistant Enterobacteriaceae (CRE) now presenting the main threat. These infections in adult populations have been associated with poor clinical outcomes, but very limited data have been published so far about risk factors and clinical outcome of ESBL-associated and CRE sepsis in the pediatric population. The treatment of these infections in neonates and children is particularly challenging due to the limited number of available effective antimicrobials. Evidence-based use of new and older antibiotics based on both strategic and regulatory clinical trials is paramount to improve management of these severe infections in neonates and children.

<p>Clinical and Molecular Epidemiologic Characteristics of Ceftazidime/Avibactam-Resistant Carbapenem-Resistant <em>Klebsiella pneumoniae</em> in a Neonatal Intensive Care Unit in China</p>

“…Due to safety concerns, carbapenems are the antibiotics of choice for treating MDR, and their widespread use has led to the global dissemination of CRKP and serious clinical outcomes in pediatric patients. [2][3][4] The prevalence of CRKP infections is also increasing among neonates and children. 5,6 Ceftazidime/avibactam (CZA), a new combination of cephalosporin and avibactam, a β-lactamase inhibitor, approved by US Food and Drug Administration (FDA) in 2015 and the European Medicines Agency (EMA) in 2016, has shown high activity against Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae (K. pneumoniae).…”

<p>Optimal Management of Complicated Infections in the Pediatric Patient: The Role and Utility of Ceftazidime/Avibactam</p>

“…Despite the increased global attention to MDR-GN, little research has been conducted on these infections in children, the few available data suggest that MDR-GN epidemiology, risk factors, and outcomes are comparable with those observed in adults. 8 Nosocomial outbreaks have been reported in neonatal and pediatric intensive care units and the geographical distribution was generally consistent with adults patients one. 8 Bacterial surveillance, strategies for implementing effective infection-prevention, and antimicrobial stewardship programs specifically for children are needed.…”

“…8 Nosocomial outbreaks have been reported in neonatal and pediatric intensive care units and the geographical distribution was generally consistent with adults patients one. 8 Bacterial surveillance, strategies for implementing effective infection-prevention, and antimicrobial stewardship programs specifically for children are needed.…”

Clearance of ESKAPE Pathogens from Blood Using Bacterially Activated Macrophage Membrane‐Coated Silicon Nanowires

“…Sepsis is a life‐threatening, systemic infection of the blood stream and is the first cause of death in critically ill patients. [ 1 ] Blood stream infections occur in North America and Europe with an incidence between 113 and 204 per 100 000 population, including neonates and children, [ 2 ] which is higher, e.g., than type I diabetes. [ 3 ] Bacterial sepsis can be caused by different Gram‐positive and Gram‐negative strains, [ 3 ] which include all multidrug resistant members of ESKAPE panel pathogens considered most threatening to human health.…”

“…with an incidence between 113 and 204 per 100 000 population, including neonates and children, [2] which is higher, e.g., than type I diabetes. [3] Bacterial sepsis can be caused by different Grampositive and Gram-negative strains, [3] which include all multidrug resistant members of ESKAPE panel pathogens considered most threatening to human health.…”