Reducing Duration of Antibiotic Use for Presumed Neonatal Early-Onset Sepsis in Greek NICUs. A “Low-Hanging Fruit” Approach

Abstract

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a “low-hanging fruit” approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016–06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [−45.33, −12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a “low-hanging fruit” approach. In resource-limited settings, similar targeted stewardship interventions can be applied.

Fighting Antimicrobial Resistance in Neonatal Intensive Care Units: Rational Use of Antibiotics in Neonatal Sepsis

“…Microbiome changes from antibiotics administered in early life are associated with chronic diseases in later life. The prolonged antibiotic exposure of premature neonates is associated with an increased risk of LOS, increased morbidity and mortality, and an increased risk of chronic lung disease, retinopathy of prematurity, periventricular leukomalacia, and necrotizing enterocolitis [ 13 , 65 , 73 , 74 , 75 , 76 ]. In addition, admission to the NICU for laboratory assessment and the empirical administration of antibiotics to neonates with risk factors entails the separation of the neonate from their mother, delaying the development of a maternal–neonate bond and the establishment of breastfeeding [ 13 , 65 , 74 , 75 , 76 ].…”

“…When treatment has been administered due to risk factors but the neonate remains asymptomatic and the blood cultures are negative at 36–48 h, it is reasonable to discontinue treatment. It is very unlikely that a blood culture that becomes positive after more than 48 h in an asymptomatic neonate is of clinical significance [ 13 , 73 , 76 ]. If there was a clinical impression of possible sepsis at the initiation of treatment and the blood cultures are negative, a longer duration of treatment may be justified, usually for five days [ 73 , 76 ].…”

“…It is very unlikely that a blood culture that becomes positive after more than 48 h in an asymptomatic neonate is of clinical significance [ 13 , 73 , 76 ]. If there was a clinical impression of possible sepsis at the initiation of treatment and the blood cultures are negative, a longer duration of treatment may be justified, usually for five days [ 73 , 76 ]. If blood cultures are positive, treatment should last for at least 10 days, while in the case of meningitis, treatment may be required for at least 21 days ( Table 1 ) [ 65 ].…”