title: Antimicrobial-resistant Gram-negative infections in neonates: burden of disease and challenges in treatment.
abstract: OBJECTIVE
  This review summarizes the main challenges of antimicrobial resistance (AMR) in the neonatal population with a special focus on multidrug-resistant (MDR) Gram-negative pathogens.
  
  
  RESULTS
  MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Extended-spectrum β-lactamase and carbapenem-resistant Enterobacteriaceae (CRE) have been reported as responsible for neonatal ICU outbreaks. Hospital data from low/middle-income countries show high proportions of isolates from neonates resistant to the WHO first-line and second-line recommended treatments. The spread of CRE has resulted in old antibiotics, such as colistin and fosfomycin, to be considered as alternative treatment options, despite the paucity of available data on safety and appropriate dosage.
  
  
  CONCLUSIONS
  Improved global neonatal AMR surveillance programmes including both epidemiology and clinical outcomes are critical for defining the burden and designing interventions. The optimal empiric treatment for neonatal sepsis in settings of high rates of AMR is currently unknown. Both strategic trials of older antibiotics and regulatory trials of new antibiotics are required to improve clinical outcomes in MDR-Gram-negative neonatal sepsis.
authors.affiliation: aPaediatric Infectious Disease Research Group, Institute for Infection and Immunity, St George's University of London, London, UK bPaediatric Pharmacology, University Children's Hospital Basel, Basel, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Folgori
authors.forename: Julia
authors.initials: J
authors.lastname: Bielicki
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000073182:Carbapenem-Resistant Enterobacteriaceae; D003091:Colistin / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D005578:Fosfomycin / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D001618:beta-Lactamases; D003091:Colistin