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Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management
Dustin D Flannery1,2,3, Kathleen Chiotos4,5,6,7,8, Jeffrey S Gerber4,5,6
1Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. flanneryd@chop.edu.
Insights
Multidrug-resistant gram-negative infections, including extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE), are a growing threat to vulnerable infants in neonatal intensive care units. Addressing this requires better surveillance, prevention, and targeted antibiotic strategies.
Area of Science:
- Neonatal Intensive Care Unit (NICU) infections
- Infectious Diseases
- Microbiology
Background:
- Neonatal intensive care unit (NICU) infants, especially preterm infants, face high infection risks due to immature immunity, prolonged hospitalization, and invasive devices.
- Multidrug-resistant gram-negative (MDR-GN) infections are increasingly prevalent in neonatal settings, jeopardizing advances in neonatal care.
- Rising antibiotic resistance in common neonatal pathogens complicates the management of suspected and confirmed infections.
Purpose of the Study:
- To review the epidemiology of MDR-GN infections in neonates globally, focusing on extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE).
- To discuss risk factors, resistance mechanisms, and current treatment recommendations for neonatal MDR-GN infections.
- To highlight best practices for prevention and identify research gaps in this critical area.
Main Methods:
- Comprehensive review of published single-center studies.
- Analysis of neonatal collaborative reports and national surveillance data.
- Synthesis of information on epidemiology, risk factors, resistance mechanisms, treatment, and prevention.
Main Results:
- Emerging evidence indicates a rise in MDR-GN infections, specifically ESBL-producing Enterobacterales and CRE, in neonatal populations.
- Established risk factors and mechanisms of resistance are discussed in the context of neonatal infections.
- Current recommendations for empiric and definitive antibiotic therapy are presented, alongside prevention strategies.
Conclusions:
- Surveillance and prevention of MDR-GN infections are critical pediatric research priorities.
- The increasing prevalence of these resistant infections poses a significant challenge to neonatal care.
- Further research is needed on the impact of MDR-GN infections on neonatal outcomes and on the pharmacokinetics of antibiotic therapies in neonates.
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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