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. Additionally, we discuss current recommendations for empiric antibiotic therapy for suspected infections, as well as definitive treatment options for key multidrug resistant organisms. Finally, we review best practices for prevention and identify current knowledge gaps and areas for future research.

Multicenter Genomic Analysis of Carbapenem-Resistant Klebsiella pneumoniae from Bacteremia in China

“…In our study, early onset infection caused by CRKP presented in premature neonates, which is one of the main risk factors for infection caused by MDR-GN bacteria ( 21 ). Additional patient and center level risk factors for MDR infection include maternal or neonatal MDR colonization, invasive devices, history of prior unit outbreak, suboptimal infection control practices, and high antibiotic consumption ( 22 ). In hospitals where CRKP transmission was detected, maternal and infant screening for CRE carriage could lead to early detection and implementation of eradication measures to prevent new cases of transmission.…”

Surveillance of carbapenem-resistant Klebsiella pneumoniae in a paediatric hospital in China revealed the dynamics of carbapenemase and the prevalence of ST2735 K. pneumoniae

“…Paediatric patients are naturally vulnerable to fatal CRKP infections and get limited treatment options due to certain antibiotics with side effects, such as nephrotoxicity and ototoxicity [12]. Carbapenem resistance has been increasingly detected in paediatric wards, with high mortality reported [13–15]. In 2017, the European survey on carbapenemase-producing Enterobacteriaceae (CPE) has revealed that 37 % of the K.…”

Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden

“…Neonatal care units (NICUs) frequently experience spread of Enterobacteriaceae [5] and outbreaks involving OXA-48-producing Enterobacteriaceae strains in this setting have been reported [6][7][8]. Due to sparse colonization by anaerobic bacteria during the first weeks of life, members of the Enterobacteriaceae family establish and reach high abundance levels in the neonatal gut.…”