Increased CD11b-Density on Circulating Phagocytes as an Early Sign of Late-Onset Sepsis in Extremely Low-Birth-Weight Infants

Turunen, Riitta; Andersson, Sture; Nupponen, Irmeli; Kautiainen, Hannu; Siitonen, Sanna; Repo, Heikki

doi:10.1203/01.pdr.0000148717.59861.2c

Cited by 53 publications

(52 citation statements)

References 46 publications

(41 reference statements)

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“…This is in contrast to the majority of other infection biomarker studies for which patients are usually recruited shortly after clinical presentation (9,12,13 ). Thus, diagnostic utilities derived from these studies would also reflect the clinical assessment skills of frontline neonatologists who decided whether or not to recruit the patients.…”

Section: Discussionmentioning

confidence: 99%

“…Further, because it is now recognized that intense immunoreactive responses associated with systemic infection may affect distant organs, especially the central nervous system (11 ), it is plausible that commencing appropriate antibiotic treatment even earlier than clinical presentation may achieve better outcomes. Very few studies have investigated the use of infection biomarkers as surveillance tools for detection of late-onset sepsis (LOS)/ NEC before clinical presentation (12,13 ). To qualify as a clinically useful surveillance biomarker, many criteria need to be satisfied, including a very small blood sample requirement to allow daily assays, good agreement of results between venous and capillary blood samples, short laboratory turnaround time, and favorable clinical utility measures (sensitivity, specificity, and predictive values) (14 ).…”

mentioning

confidence: 99%

“…To qualify as a clinically useful surveillance biomarker, many criteria need to be satisfied, including a very small blood sample requirement to allow daily assays, good agreement of results between venous and capillary blood samples, short laboratory turnaround time, and favorable clinical utility measures (sensitivity, specificity, and predictive values) (14 ). Studies evaluating surveillance biomarkers have been notoriously difficult to perform and only a few reports are available in the literature (12,13 ). Of the biomarkers investigated, quantitative measurement of neutrophil CD64 by flow cytometry fulfilled most, if not all, of the criteria of a potential biomarker for daily surveillance of LOS/NEC in highrisk preterm infants (3,10,15 ).…”

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confidence: 99%

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Neutrophil CD64 for Daily Surveillance of Systemic Infection and Necrotizing Enterocolitis in Preterm Infants

et al. 2013

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BACKGROUND Early detection and treatment of infected preterm infants could decrease morbidity and mortality. Neutrophil CD64 has been shown to be an excellent early diagnostic biomarker of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). We aimed to study whether using CD64 as a daily surveillance biomarker could predict LOS/NEC before clinical manifestation. METHODS We collected 0.1 mL whole blood from very low birth weight (VLBW) infants from day 7 postnatal age until routine daily blood tests were no longer required. Four categories of responses were defined: proven sepsis, clinical sepsis, nonsepsis/non-NEC, and asymptomatic CD64 activation. RESULTS A total of 146 infants were consecutively recruited and 155 episodes of sepsis evaluation were performed. The biomarker screening utility, sensitivity, specificity, positive predictive value, and negative predictive value for surveillance of LOS/NEC using a cutoff of 5655 antibody-PE (phycoerythrin) molecules bound/cell were 89%, 98%, 41%, and 99.8%, respectively. LOS/NEC was detected a mean of 1.5 days before clinical presentation. However, 63 episodes of CD64 activation occurred in asymptomatic infants who would not otherwise have required sepsis evaluations. CONCLUSIONS As a surveillance biomarker, neutrophil CD64 detected LOS/NEC 1.5 days before clinical presentation, but at the expense of performing 41% additional sepsis evaluations. This was mainly attributed to an unexpected group of asymptomatic infants with CD64 activation, who recovered spontaneously and did not require antimicrobial treatment. The latter group has not been previously recognized in VLBW infants and could represent subclinical infection secondary to transient bacterial translocation or mild viral infection.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Neutrophil CD64 for Daily Surveillance of Systemic Infection and Necrotizing Enterocolitis in Preterm Infants

et al. 2013

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“…Cell surface antigens that have been studied by flow cytometry in recent years with respect to congenital, early-and lateonset sepsis include CD11b, Fcγ receptors I-III (CD64, CD32, CD16), and CD69 [34][35][36][37]. Blood specimens for cell surface markers should be transported to the laboratory on ice and processed immediately: Studies showed that a substantial proportion of neutrophils undergoes apoptosis after 24 h and down-regulates surface receptor antigens during the apoptotic process [36,37].…”

Section: Clinical Studies On Cellular Targets In Neonatal Infectionmentioning

confidence: 99%

Flow Cytometric Methods in the Detection of Neonatal Infection

Gille

Orlikowsky²

2007

Transfus Med Hemother

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Bacterial infection remains the main cause of neonatal morbidity and mortality. With clinical signs unspecific and little, its course is fulminant, and only early antibiotic therapy protects from death or major adverse sequelae. Methods: Conventional diagnostic tests have shortcomings and are only partly suitable to identify infected vs. non-infected newborns. There is a fast increasing demand for standardized flow cytometric techniques in the detection of neonatal infection which require minimal amounts of blood. Target cells are monocytes/ macrophages, granulocytes and NK cells. Results: The choice of receptors and interpretation of results need to be done carefully: A variety of receptors are expressed differently, basally or upon cytokine-mediated regulation, in full- or preterm neonates than in adults, and their expression is influenced by perinatal confounders. Examples are HLA-DR, CD80, CD86, CD16, CD32 receptors on monocytes/macrophages. Flow cytometric measurement of CD11b and CD64 expression on phagocytes combined with cytokine (IL-6 or IL-8) or C-reactive protein measurement in plasma or whole blood have turned out to be most sensitive and specific markers for detecting early- and late-onset bacterial infection. Conclusion: To date, no flow cytometric marker or set of markers is sensitive and specific enough to allow neonatologists to withhold antibiotic treatment of a sick neonate who is suspected to be infected.

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“…Over the past decades, neonatologists have identified immunomodulating mediators and utilized them as surrogate markers for early diagnosis and predicting the severity of systemic infection and necrotizing enterocolitis (NEC), [3,4,5]. With progressive advancement in biochemical/genetic research, more sophisticated classes of biomarkers are identified, including cytokines [6], chemokines [3,4], cell surface antigens [7,8,9], and Gram-positive and Gram-negative organism-specific nucleic acids [10]. More recently, we have entered into a new era of searching for ‘novel’ as well as ‘specific’ biomarkers for individual diseases, organ injury, or even monitoring disease activity in a specific region within an organ.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers in Neonatology: The Next Generation of Tests

Lam²

2012

Neonatology

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Over the past two decades, neonatal clinicians have commonly used host response biomarkers to diagnose and assess the severity of systemic infection. Most of these biomarkers, such as acute-phase proteins or cytokines, are non-specific immunomodulating mediators of the inflammatory cascade. With advances in biochemical/genetic research, it is anticipated that future biomarkers will be ‘organ and/or disease specific’. There is also the quest for discovery of ‘novel’ biomarkers to assist diagnosis and prognosis of neonatal diseases using powerful mass-screening techniques, e.g. the next-generation sequencing, proteomics and arrays. This article aims to introduce the concept of the next generation of biomarkers to practising neonatal clinicians, and, hopefully, to integrate basic science research into day-to-day clinical practice in the future.

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Increased CD11b-Density on Circulating Phagocytes as an Early Sign of Late-Onset Sepsis in Extremely Low-Birth-Weight Infants

Cited by 53 publications

References 46 publications

Neutrophil CD64 for Daily Surveillance of Systemic Infection and Necrotizing Enterocolitis in Preterm Infants

Neutrophil CD64 for Daily Surveillance of Systemic Infection and Necrotizing Enterocolitis in Preterm Infants

Flow Cytometric Methods in the Detection of Neonatal Infection

Biomarkers in Neonatology: The Next Generation of Tests

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