Late-onset sepsis in preterm infants: update on strategies for therapy and prevention

Abstract

Late-onset sepsis occurs in 15–25% of very low birth weight neonates. Early diagnosis and therapy optimize patient outcomes. Despite these efforts, mortality remains high (18–36%) and survivors suffer significant neurological and pulmonary morbidity. Although rapid diagnostics are improving, more are needed. Current therapy remains antibiotics and supportive care. Adjunctive therapies have either limited data (e.g., pentoxifylline) or have been found ineffective (e.g., granulocyte transfusions, granulocyte macrophage colony-stimulating factor/granulocyte colony-stimulating factor, and intravenous immunoglobulin). Preventive strategies that have proven beneficial include infection control measures (e.g., hand hygiene and universal precautions), early enteral feeds with human milk, early removal of central lines, catheter infection prevention bundles, antibiotic stewardship and focused quality improvement measures. Promising strategies to prevent late-onset sepsis include oral lactoferrin, and pathogen-specific monoclonal antibodies but more evidence is required to make practice recommendations.

Keywords:

• diagnosis
• neonate
• outcomes
• prevention
• sepsis
• treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Neonatal sepsis remains a major cause for neonatal mortality and morbidity in preterm and very low birth weight infants despite improvement in neonatal practices and knowledge.

• General supportive care includes providing optimal oxygenation, adequate perfusion and a thermoneutral environment. We recommend removal of catheters that may be foci of bacterial infection within 48 h after the diagnosis of sepsis is made. Failure or delay in catheter removal is associated with an increased risk of complications and persistent bacteremia.

• We recommend initial empirical antibiotic therapy for preterm infants with suspected sepsis that provides broad coverage for the most likely pathogens. The recommended regimen for LOS in preterm infants during the birth hospitalization (primarily due to coagulase-negative staphylococci, followed by S. aureus and Gram-negative bacteria) is vancomycin and an aminoglycoside (most commonly gentamicin). Alternative regimens may substitute nafcillin or oxacillin for vancomycin to decrease vancomycin exposure. Antibiotic therapy is optimized after the isolation of the causative agent and determination of its antimicrobial susceptibility pattern.

• The duration of therapy is dependent upon the results of blood culture and clinical course: In infants with a positive blood culture, we suggest a 10-day course of antibiotic therapy. In well-appearing infants with a negative culture after 48 h, we suggest that empiric antibiotic therapy be discontinued, as it is likely the infants are not septic.

• Evidence suggests that pentoxifylline as an adjunct to antibiotics may improve the short-term outcomes after sepsis. However, further studies are needed before this can be considered a routine treatment. Other forms of adjunctive immunotherapy in neonatal sepsis with intravenous immunoglobulin, granulocyte transfusion, granulocyte and granulocyte-macrophage colony-stimulating factor have been shown to be ineffective.

• Prevention of sepsis should be our focus with implementation of infection control measures including hand hygiene, adherence to guidelines for the insertion and maintenance of indwelling lines to prevent central-line infections to reduce the incidence of sepsis and judicious use of antibiotic therapy.

• Current evidence suggests lactoferrin may be effective in preventing late-onset sepsis, but further studies are needed before they become routine practices.