Monocyte CD64 does not enhance neutrophil CD64 as a diagnostic marker in neonatal sepsis

The Pediatric Infectious Disease Journal  •  Volume 33, Number 10, October 2014

Letters

Felice C. Adler-Shohet, MD

Infectious Diseases Children’s Hospital Orange County Orange, CA

Julie Low, MD Michael Carson, MS Haimanot Girma, MPH

County of Orange Health Care Agency Santa Ana, CA

Jasjit Singh, MD

Infectious Diseases Children’s Hospital Orange County Orange, CA REFERENCES 1. Seddon JA, Hesseling AC, Finlayson H, et al. Preventive therapy for child contacts of multidrug-resistant tuberculosis: a prospective cohort study. Clin Infect Dis. 2013;57:1676–1684. 2. Adler-Shohet FC, Low J, Carson M, et al. Management of latent tuberculosis infection in child contacts of multidrug-resistant tuberculosis. Pediatr Infect Dis J. 2014;33:664–666. 3. Ridzon R, Meador J, Maxwell R, et al. Asymptomatic hepatitis in persons who received alternative preventive therapy with pyrazinamide and ofloxacin. Clin Infect Dis. 1997;24:1264–1265. 4. Papastavros T, Dolovich LR, Holbrook A, et al. Adverse events associated with pyrazinamide and levofloxacin in the treatment of latent multidrug resistant tuberculosis. CMAJ. 2002;167:131–136.

Monocyte CD64 Does Not Enhance Neutrophil CD64 as a Diagnostic Marker in Neonatal Sepsis To The Editors: e were intrigued by the recent paper that suggested that monocyte CD64 (mCD64) could enhance the ability of neutrophil CD64 (nCD64) as a diagnostic marker for neonatal sepsis, when expressed as median m/n CD64 values.1 As part of our recent investigations into

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Biostatistical collaboration was provided through CTSA Grant Number UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on Re-engineering the Clinical Research Enterprise can be obtained from the NIH website. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3310-1100 DOI: 10.1097/INF.0000000000000411

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FIGURE 1. Simple correlation between neutrophil and mCD64, regardless of repeated measurements. R = 0.75; P < 0.0001. the role of nCD64 as a diagnostic marker for neonatal sepsis,2,3 we had also collected data on mCD64 measurements. Hence, we went back to analyze our mCD64 data to assess whether it would improve our diagnostic abilities. We had 919 episodes of sepsis evaluations with both nCD64 and mCD64 measurements available. Of these 919, 533 episodes were of early-onset sepsis, of which 2 were culture proven. Of 386 episodes of late-onset sepsis, 46 were culture proven. Hence, we had a total of 48 episodes of culture-proven sepsis available for analysis. As we have done previously,2,3 we generated area under the curve (AUC) for receiver operator characteristic curves using nCD64 and mCD64, controlling for birth weight as a predictor. We found similar values for the AUC 0.88 and 0.82 for nCD64 and mCD64, respectively. Combining the two, even when they were correlated, gave similar results; an AUC of 0.88. We also calculated the AUC using the m/nCD64 ratio and obtained a result of 0.83. This value was similar to that of mCD64 alone, but less than that of nCD64 alone. Next, we performed a simple correlation of nCD64 and mCD64, regardless of repeated measurements, and obtained an R = 0.75, P < 0.0001 (Fig. 1). We concluded

This work was supported in part by an unrestricted educational grant from Trillium Diagnostics to H.M.R. Trillium Diagnostics and its employees were not involved in the design and conduct of the study; collection, management, analysis and interpretation of the data and preparation, review or approval of the manuscript. No honorarium, grant or other form of payment was given to anyone to produce the manuscript. The authors have no other funding or conflicts of interest to disclose.

that mCD64 appeared to have no additional value in predicting culture-proven neonatal sepsis compared with nCD64 measurements. Our results support reports by other investigators where the mCD64 performed on par or below that of nCD64 as a diagnostic marker for neonatal sepsis.4,5 We speculate the differences in our results, compared with the earlier study,1 could be because of the different methodology used for measuring and analyzing mCD64. Our monocyte and neutrophil CD64 values were generated using a different antibody and were derived using an additional isotype control-based index to control for nonspecific fluorescence, often a significant issue for quantitating monocyte surface marker fluorescence. In addition, the differences in the types of microorganisms (which could instigate variable response in the n and/or m CD64 expression) isolated from the neonates at these 2 sites could also be another potential reason for the discrepant results. Additional studies are required to assess the utility, if any, of mCD64 in addition to that of nCD64, in the diagnosis of neonatal sepsis.

Fang-Yong Li, MPH Veronika Shabanova, MPH Yale Center for Analytical Sciences

Chao Wang, BS Henry M. Rinder, MD Department of Laboratory Medicine Yale University School of Medicine

Vineet Bhandari, MD, DM Division of Perinatal Medicine Department of Pediatrics Yale University School of Medicine New Haven, CT © 2014 Lippincott Williams & Wilkins

The Pediatric Infectious Disease Journal  •  Volume 33, Number 10, October 2014

REFERENCES 1. Soni S, Wadhwa N, Kumar R, et al. Evaluation of CD64 expression on neutrophils as an early indicator of neonatal sepsis. Pediatr Infect Dis J. 2013;32:e33–e37. 2. Streimish I, Bizzarro M, Northrup V, et al. Neutrophil CD64 as a diagnostic marker in neonatal sepsis. Pediatr Infect Dis J. 2012;31:777–781.

© 2014 Lippincott Williams & Wilkins

3. Streimish I, Bizzarro M, Northrup V, et al. Neutrophil CD64 with hematologic criteria for diagnosis of neonatal sepsis. Am J Perinatol. 2014;31:21–30. 4. Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, et al. Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of

Letters

critically ill neonates and children. Intensive Care Med. 2009;35:1950–1958. 5. Genel F, Atlihan F, Gulez N, et al. Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection. World J Pediatr. 2012;8:72–75.

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