Exploring the use of cluster analysis to assess antibiotic stewardship in critically-ill neonates in a low resource setting

Abstract

Abstract Background: Sepsis is the third leading cause of neonatal death in low and middle-income countries, accounting for one third of all deaths in Ethiopia. A concerning issue is the increasing number of multidrug-resistant microorganisms facilitated by suboptimal antibiotic stewardship. The study aims to identify clusters of newborns switching antibiotic lines for sepsis in a neonatal intensive care unit (NICU) in Ethiopia, and to explore their potential association with sepsis outcomes. Methods: A retrospective cohort study was conducted including all newborns discharged with a diagnosis of probable neonatal sepsis from the St. Luke Catholic Hospital NICU between April and July 2021. The antibiotic management protocol included two lines according to WHO guidelines and a third line based on internal hospital guidelines. In the cluster analysis, the Gower distance was estimated based on the antibiotics employed in the different lines and the duration of each line. Mortality and respiratory distress (RD) were the response variables. Results: In the study period, 456 newborns were admitted to the NICU and 196 (42.8%) had probable neonatal sepsis. Four antibiotic management clusters were identified. Cluster 1 (n=145, 74.4%) had no antibiotic switches, using only the first line. Cluster 2 (n=26, 13.3%) had one switch from the first to the second line. Cluster 4 (n=9, 4.6%) had two switches: from first to second and then to third line. In cluster 3 (n=15, 7.7%), newborns were switched from ceftriaxone/cloxacillin as second line to off-protocol antibiotics. There were no differences in sex, age, weight on admission or crude mortality between clusters. Cluster 3 included a higher frequency of infants who did not breathe at birth (53.3%, p=0.011) and that necessitated bag ventilation (46.7%, p=0.039) compared to the other clusters. The RD odds ratio (OR) was higher in cluster 3 than in clusters 1 (OR=0.09[0.01-0.36] p=0.003) and 2 (OR=0.13[0.02-0.64] p=0.022). Conclusions: The first antibiotic line failed one out of four newborns with sepsis while third-generation cephalosporins were insufficient in 12.3% of patients. Cluster analysis can be a useful tool for identifying patients who need antibiotic switches and their characteristics.