What are the laboratory results for a diagnosis of neonatal sepsis?

From the Guidelines

Neonatal sepsis laboratory evaluation should include a complete blood count (CBC) with differential, blood culture, C-reactive protein (CRP), and procalcitonin, with early antibiotic therapy initiated based on clinical suspicion without waiting for all laboratory results, as delayed treatment increases mortality risk in neonatal sepsis. The CBC may show leukopenia (white blood cell count <5,000/μL) or leukocytosis (>30,000/μL in the first week of life), thrombocytopenia (platelets <100,000/μL), and an elevated immature-to-total neutrophil ratio (I:T ratio >0.2) 1. Blood cultures are the gold standard for diagnosis but may take 24-48 hours for results. CRP levels typically rise 6-8 hours after infection onset and peak at 24-48 hours; values >10 mg/L are concerning. Procalcitonin increases within 2-4 hours of infection with levels >2 ng/mL suggesting bacterial infection. Additional tests may include cerebrospinal fluid analysis if meningitis is suspected, urine culture if the infant is >72 hours old, and chest X-ray if respiratory symptoms are present. These laboratory findings must be interpreted in the clinical context, as no single test is perfectly sensitive or specific. According to the most recent guidelines, the first-line empirical treatment for neonatal sepsis should be based on the most common pathogens encountered, with antibiotics such as amoxicillin, ampicillin, and benzylpenicillin chosen for their activity against group B Streptococcus, and aminoglycosides (i.e., gentamicin) for their activity against Gram-negative bacteria 1. The recommended empirical treatment for late-onset neonatal sepsis varied between guidelines, reflecting different patterns of antibiotic resistance and pathogens reported globally. The World Health Organization (WHO) recommends the use of gentamicin with either ampicillin or benzylpenicillin as first-line treatment for neonatal and pediatric sepsis in resource-limited settings, with ceftriaxone as recommended second-line therapy 1. Key laboratory findings and their interpretations include:

• Leukopenia or leukocytosis
• Thrombocytopenia
• Elevated I:T ratio
• Positive blood culture
• Elevated CRP and procalcitonin levels It is essential to note that the choice of empirical antibiotic therapy should be based on local antimicrobial resistance patterns and the most likely causative pathogens. In cases where hospital care is not possible, procaine benzylpenicillin may be considered as a first-line treatment for neonatal sepsis, but only when given by trained healthcare workers in settings with high neonatal mortality 1. The use of antibiotics such as cefotaxime and ceftriaxone as second-line choices should be guided by local resistance patterns and the severity of the infection. Ultimately, the goal of laboratory evaluation and antibiotic therapy in neonatal sepsis is to reduce morbidity, mortality, and improve quality of life, and this should be achieved through a combination of prompt and effective treatment, as well as careful consideration of the clinical context and local epidemiology.

From the Research

Neonatal Sepsis Lab Results

• Blood culture is considered the gold standard for diagnosing neonatal sepsis 2, 3
• Laboratory tests have low value in suspected neonatal sepsis, with less than 10% and no more than 25%-30% of newborns with suspected sepsis actually having proven neonatal sepsis 2
• Commonly involved bacteria in neonatal sepsis include Staphylococcus aureus and Escherichia coli 3
• Risk factors for neonatal sepsis include central venous catheter use and prolonged hospitalization 3
• Immediate treatment with antibiotics is imperative for neonatal sepsis, but stopping them can be difficult despite little or no support to maintain them 2, 4

Antibiotic Therapy

• The use of targeted antibiotics is essential as soon as the pathogen in the culture is detected 4
• Empiric antibiotic regimens should be affordable, active against neonatal bacterial pathogens, and have minimal toxicities 5
• Alternative empiric antibiotic regimens are being developed to address the growing problem of multidrug-resistant bacteria in neonatal sepsis 5
• Five antibiotics that fulfill the criteria for alternative empiric regimens are amikacin, tobramycin, fosfomycin, flomoxef, and cefepime 5

Treatment Outcomes

• The use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death 6
• Factors associated with death in neonates treated with antibiotics include immature gestational age, need for assisted ventilation, and indications of perinatal asphyxia or major congenital anomaly 6