Culture-Negative Early-Onset Neonatal Sepsis — At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship

Abstract

Sepsis is a leading cause of mortality and morbidity in neonates. Presenting clinical symptoms are unspecific. Sensitivity and positive predictive value of biomarkers at onset of symptoms are suboptimal. Clinical suspicion therefore frequently leads to empirical antibiotic therapy in uninfected infants. The incidence of culture confirmed early-onset sepsis is rather low, around 0.4–0.8/1000 term infants in high-income countries. Six to 16 times more infants receive therapy for culture-negative sepsis in the absence of a positive blood culture. Thus, culture-negative sepsis contributes to high antibiotic consumption in neonatal units. Antibiotics may be life-saving for the few infants who are truly infected. However, overuse of broad-spectrum antibiotics increases colonization with antibiotic resistant bacteria. Antibiotic therapy also induces perturbations of the non-resilient early life microbiota with potentially long lasting negative impact on the individual‘s own health. Currently there is no uniform consensus definition for neonatal sepsis. This leads to variations in management. Two factors may reduce the number of culture-negative sepsis cases. First, obtaining adequate blood cultures (0.5–1 mL) at symptom onset is mandatory. Unless there is a strong clinical or biochemical indication to prolong antibiotics physician need to trust the culture results and to stop antibiotics for suspected sepsis within 36–48 h. Secondly, an international robust and pragmatic neonatal sepsis definition is urgently needed. Neonatal sepsis is a dynamic condition. Rigorous evaluation of clinical symptoms (“organ dysfunction”) over 36–48 h in combination with appropriately selected biomarkers (“dysregulated host response”) may be used to support or refute a sepsis diagnosis.

Can we optimize antibiotic use in Norwegian neonates? A prospective comparison between a university hospital and a district hospital

“…However, our rate is low, compared to international literature (28)(29)(30). The relation between culture-positive and culture-negative sepsis (term infants, EOS) in our population (1:10) is in the published range (31), while the numbers needed to treat for one positive culture [60] is at the lower side of the literature (11,32). Our rate of antibiotic exposure for extremely premature infants is in line with data from the USA (33).…”

Antibiotic prescribing in neonatal sepsis: an Australian nationwide survey

“…Over 20% of antibiotics had been prescribed for >48 hours at time of audit, although only 4% of neonates had microbiologically confirmed infection documented. Given that the majority of potential pathogens in neonatal sepsis are identified within 36-48 hours, 34 this may represent excessive antibiotic therapy and provides an opportunity for quality improvement. Hospital antimicrobial stewardship teams may not include neonatal pharmacologists or neonatal infection specialists, and thus the recently nationally available guidelines for sepsis and antimicrobial use in neonates, listed above, may provide a more robust framework for assessment and promotion of the most appropriate therapy.…”

Neonatal Sepsis

“…EONS is typically described as infection and sepsis occurring within the first 24 hours to first week of life [1][2][3]. LONS has been labeled as after 24 hours or after the first week of life, up to 28 days or 1 month [4][5][6]. The literature varies in the definition of EONS and LONS, but most categorize EONS as within the first 72 hours of life and LONS as after this time period up to 28 days [7][8][9][10].…”