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ARI 2022 Call for Proposals: inflammation and sepsis

Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management

Abstract

Infants admitted to the neonatal intensive care unit, particularly those born preterm, are at high risk for infection due to the combination of an immature immune system, prolonged hospitalization, and frequent use of invasive devices. Emerging evidence suggests that multidrug-resistant gram-negative (MDR-GN) infections are increasing in neonatal settings, which directly threatens recent and ongoing advances in contemporary neonatal care. A rising prevalence of antibiotic resistance among common neonatal pathogens compounds the challenge of optimal management of suspected and confirmed neonatal infection. We review the epidemiology of MDR-GN infections in neonates in the United States and internationally, with a focus on extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE). We include published single-center studies, neonatal collaborative reports, and national surveillance data. Risk factors for and mechanisms of resistance are discussed. In addition, we discuss current recommendations for empiric antibiotic therapy for suspected infections, as well as definitive treatment options for key MDR organisms. Finally, we review best practices for prevention and identify current knowledge gaps and areas for future research.

Impact

  • Surveillance and prevention of MDR-GN infections is a pediatric research priority.

  • A rising prevalence of MDR-GN neonatal infections, specifically ESBL-producing Enterobacterales and CRE, compounds the challenge of optimal management of suspected and confirmed neonatal infection.

  • Future studies are needed to understand the impacts of MDR-GN infection on neonatal morbidity and mortality, and studies of current and novel antibiotic therapies should include a focus on the pharmacokinetics of such agents among neonates.

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Funding

D.D.F. reports receiving research funding from the Agency for Healthcare Research and Quality (AHRQ) (K08HS027468), from two contracts with the Centers for Disease Control and Prevention (CDC), and from the Children’s Hospital of Philadelphia (CHOP). K.C. reports receiving research funding through AHRQ (K12HS026393). K.M.P. reports receiving research funding from the National Institutes of Health (NIH), from two contracts with the CDC, and from CHOP. The funders/sponsors had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

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D.D.F. conceptualized the review article, drafted the initial manuscript, and reviewed and revised the manuscript. K.C. conceptualized the review article, contributed to the initial manuscript, and reviewed and revised the manuscript. J.S.G. and K.M.P. conceptualized the review article and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Dustin D. Flannery.

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Flannery, D.D., Chiotos, K., Gerber, J.S. et al. Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management. Pediatr Res 91, 380–391 (2022). https://doi.org/10.1038/s41390-021-01745-7

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