Risk Factors Associated with Multi-Drug Resistance in Neonatal Sepsis Caused by Escherichia coli

Minli Zhu,1 Leying Wang,1 Zhangming Zhuge,1 Wei Li,1,2 Yihui Zheng,1 Jingyun Mai,1 Zhenlang Lin,1 Jing Lin1,3 1Key Laboratory of Perinatal Medicine of Wenzhou, Department of Neonatology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2Zhijin People’s Hospital of Guizhou Province, Guizhou, 552100, People’s Republic of China; 3Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USACorrespondence: Jing Lin, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA, Tel +1-212-241-6186, Fax +1-212534-5207, Email jing.lin@mssm.edu Zhenlang Lin, Department of Neonatology, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86 13806689800, Email linzhenlang@hotmail.comBackground and Objective: An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics.Patients and Methods: All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis.Results: ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184– 199.326, P< 0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009– 10.055, P< 0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis.Conclusion: E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility.Keywords: infant, newborn, neonatal sepsis, Escherichia coli, drug resistance, extended-spectrum beta-lactamase