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Neutrophil counts appear critical to sepsis management
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Enhanced neutrophil CD64, or nCD64, may be an important marker for diagnosing infants with sepsis and may help serve as a guide for clinicians about the best antibiotics for these infants, according to study data published online.
Neelam Wadhwa, MD, of the department of pathology at the University College of Medical Sciences and the University of Delhi, India, and colleagues reported on 90 infants, including 24 who had culture-positive sepsis and 36 who were culture negative.
The researchers said the infants with confirmed sepsis had “significantly higher mean and median nCD64 expression compared with controls.”
The investigators also said, “Median M/N CD64 ratio was the best discriminant by virtue of highest area under the receiver operator characteristic curve (0.903), with sensitivity and specificity of 91.7% and 88.9% respectively.”
Wadhwa and colleagues said because sepsis is a leading cause of mortality in infants in India each year, isolating the pathogenic organism and developing systems to identify sepsis are critical to providing the right treatment.
“The new generation of early indicators of neonatal sepsis includes measurement of cell activation markers, cytokine levels in blood and molecular microbiologic techniques,” the researchers wrote.
Disclosure: Wadhwa reports no relevant financial disclosures.
Perspective
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David A. Kaufman, MD
Identifying newborns with neonatal sepsis is critical for survival, neurodevelopmental outcomes, early treatment and appropriately use of antibiotics. The area of using diagnostic markers is complex, in that a marker may perform differently with early-onset sepsis (EOS) vs late-onset sepsis (LOS), may vary with type of bloodstream infection, and can be elevated with infectious processes other than bloodstream infections.
Most commonly, studies discuss the relationship of these markers with blood culture results and almost always with the caveat that the blood culture may not be 100% reliable. Rarely are short-term and long-term outcomes included in the studies. Also lacking is a discussion of the amount of blood needed for each evaluation of EOS and LOS. With CRPs, an additional 0.6 mL to 1.0 mL is needed serially (two to three times) with each work-up. For some infants weighing less than 1,000 g, they may have five sepsis evaluations. Compared to other markers, CD64 is attractive in that it can be performed from the blood remaining from the CBC or only requires 50 mcL of blood once at the time of the sepsis evaluation. A limitation is that flow cytometry is required, which may not be available 24 hours a day every day of the week. Standard cell counters that use flow cytometry have the potential to give this information rapidly.
CD64 is a high affinity Fc receptor that increases its expression on neutrophils in response to infectious stimuli. The authors have analyzed the data with insight into using an enhanced CD64 expression for the diagnosis of culture positive sepsis, which they define as the ratio of the median monocyte CD64/neutrophil CD64 expression. What they uncovered needs confirmation in other centers and in more patient groups. Examining EOS and LOS, gram-positive vs gram-negative infections, preterm and full-term infants, and accounting for other infections needs further study. For example, Streimish and colleagues in a study published this year found differences in cut off values with EOS and LOS. Also, preterm infants need to be examined across gestational ages to see if their neutrophil function (which is often underdeveloped) expresses CD64 in similar patterns.
Finally, predictive monitoring using heart rate characteristics has recently been studied in LOS in preterm infants and demonstrated using a “real time” score of heart characteristics to help guide clinical care was able to decrease mortality in patients with LOS (Moorman, 2011). This is highly desirable as it does not require any blood, evaluates the patient continuously, and has demonstrated its application can significantly reduce mortality.
The goal of diagnostic markers should be to improve our care, reduce mortality and morbidity from infection, and help guide early use of antibiotics when infectious risk is high or reduce antibiotic doses or days when infection unlikely. Otherwise our use of these markers is increasing health care cost and while decreasing the blood volume and its important components (such as stem cells) at a critical time of development in our patients.
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