Demystifying Prolonged Antibiotic Use for Blood Culture-negative Sepsis Evaluations in the Neonatal Intensive Care...

This study aimed to determine the incidence and clinical characteristics of infants evaluated and treated with a prolonged course of antibiotics for culture-negative sepsis in a quaternary Neonatal Intensive Care Unit (NICU) over a 4-year period.

Retrospective chart review of patients in the NICU at Children's Hospital of Philadelphia who had negative blood cultures and received ≥5 days of antibiotics. Data collection included demographics, clinical and laboratory data, and underlying diagnoses. Statistical analysis included Mann-Whitney and chi-square tests, and multivariable logistic regression.

We identified 774 culture-negative sepsis evaluations where antibiotic treatment was continued ≥5 days. While the majority were attributed to a focal etiology, 146 had negative blood cultures and no focal source. Infants with no focal source were younger at the time of sepsis evaluation, of greater gestational age, and more frequently required extracorporeal membrane oxygenation ( P < 0.001). In multivariable analysis, evaluations for early-onset disease and need for extracorporeal membrane oxygenation were increased among infants with no focal source ( P < 0.01). Although rates of invasive ventilation, and central venous catheters were similar, length of stay and mortality were significantly higher in late-onset episodes ( P < 0.001 and P = 0.029, respectively). Consultation with the infectious disease team increased during the study period ( P = 0.002).

Although it is challenging to limit the initiation of antibiotics in infants with complex underlying disease processes with concern for sepsis, minimizing antibiotic use can be achieved by timely discontinuation when cultures are negative. A robust antimicrobial stewardship program can identify valid reasons for prolonged antibiotic administration and suggest approaches to minimize antibiotic exposure.