Role of Neutrophil CD64 Index as a Screening Marker for Late-Onset Sepsis in Very Low Birth Weight Infants

Abstract

Introduction: The role of CD64 in late onset sepsis (LOS) in preterm infants has been described in several studies. Aim of this study was to investigate whether CD64 expression is increased in the days before clinical manifestation of LOS.

Methods: Patients with birth weight below 1,500 g were eligible for study participation. During routine blood sampling CD64 index was determined between day of life 4 and 28. Patients were allocated to one of four groups: (1) blood-culture positive sepsis, (2) clinical sepsis, (3) symptoms of infection without biochemical evidence of infection, or (4) patients without suspected infection. Kinetics of CD64 expression were compared during a period before and after the day of infection in the respective groups.

Results: 50 infants were prospectively enrolled and allocated to each group as follows: group (1) n = 7; group (2) n = 10; group (3) n = 8; and group (4) n = 25. CD64 index was elevated in 57% of patients in group (1) at least two days before infection. In contrast only 20% in the clinical sepsis group and 0% in group (3) had an elevated CD64 index in the days before infection. 10 of the 25 patients in the control group (4) presented increased CD64 index values during the study period.

Conclusions: The CD64 index might be a promising marker to detect LOS before infants demonstrate signs or symptoms of infection. However, larger prospective studies are needed to define optimal cut-off values and to investigate the role of non-infectious inflammation in this patient group.

Fig 1. Flow diagram of group allocation of the 50 infants enrolled in the study.

During the study period (i.e. day of life 4 until day of life 28), 25 infants were evaluated for sepsis. Infants with septicemia represent the culture positive group (n = 7). Infants with clinical features of infection, a negative blood culture and antibiotic treatment for at least 5 days were allocated to the clinical sepsis group (n = 10) and infants with evaluation for sepsis who were subsequently proven not to be infected were allocated to the indeterminate group (n = 8). The control group consisted of the remaining 25 infants without sepsis evaluation.

Fig 2. Cumulative incidence of infants with elevated CD64 index values during the observation period.

A CD64 index greater than 1.86 was defined as the cut-off value for infection. Day 0 indicates the day of sepsis evaluation (i.e. day of diagnosis). The bars represent the percentage of infants with a positive CD64 index from the beginning of the observation period until the respective day. The differences between groups did not reach statistical significance.

Fig 3. Median CD64 index values during the observation period.

Median CD64 index was compared for every day during the observation period (day -4 until day +5) in the respective groups using the Mann-Whitney test. Median CD64 index was significantly higher on day +1 in the culture positive group compared to the clinical sepsis group (p <0.05; *) and significantly higher in the culture positive group compared to the indeterminate group on day +3 and day +4 (p <0.05; ‡). There was no difference in median CD64 index values between the clinical sepsis group and the indeterminate group. The dashed vertical line indicates the day of diagnosis (day 0). The numbers of samples for each data point are reported in Table 3.

Fig 4. Elevation of CD64 index in asymptomatic infants in the first 28 days of life.

Proportion and absolute numbers (n) of infants with elevated CD64 index (>1.86) of all infants in the control group in whom CD64 index had been determined at the respective day between postnatal day 4 and 28 (study period).