Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection

Weirich, Erica; Rabin, Ronald L.; Maldonado, Yvonne; Benitz, William Ε.; Modler, Siv; Herzenberg, Leonard A.; Herzenberg, Leonore A.

doi:10.1016/s0022-3476(98)70018-6

Cited by 106 publications

(90 citation statements)

References 57 publications

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“…Our findings confirm the results of Berner et al 11 and Weirich et al, 17 reported while the present study was in progress, and extend them to show that the markers provide a means to distinguish infected infants with systemic inflammation from the symptomatic infants who have a noninfective disorder without systemic inflammation. Although Weirich et al 17 excluded from their study infants with noninfective disorders, we focused on such infants because discrimination between sepsis and a noninfective disorder, both result in identical clinical signs, is crucial in clinical decision-making.…”

Section: Discussionsupporting

confidence: 93%

“…27 When stimulated in vitro with FMLP, a neutrophil agonist, neutrophils from neonates show a reduced ability to enhance CD11b expression. 28 -32 The results in the present study and the previous study 17 show, on the first day of life, a two-to fourfold increase in neutrophil CD11b expression in infants with blood-culture positive sepsis. This increase is similar to that demonstrated in neutrophils from adults with blood-culture positive sepsis.…”

Section: Discussionsupporting

confidence: 56%

“…IL-8 and CD11b are both superior to CRP in the detection of systemic inflammation at its early stage, as shown by the results in the present study and multiple previous studies. 11,12,17,43 CRP may, however, serve as a criterion for discontinuation of antibiotic therapy, and when used as the guide to treatment, can decrease antimicrobial consumption, at least in some clinical settings. 47 Recently, IL-8 was found to reduce in a cost-effective manner unnecessary antibiotic therapy for nosocomial bacterial infection in newborn infants by 73%.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 This increase in CD11b/CD18 expression occurs in adults with sepsis, 9,16 and as demonstrated recently, in neonates with early-onset sepsis. 17 IL-8 12 and CD11b expression 17 both proved to be superior to C-reactive protein (CRP), an acute phase reactant, in detection of neonatal sepsis.…”

mentioning

confidence: 99%

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Neutrophil CD11b Expression and Circulating Interleukin-8 as Diagnostic Markers for Early-Onset Neonatal Sepsis

et al. 2001

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ABSTRACT. Objective. To assess neutrophil CD11b and circulating interleukin 8 (IL-8) as markers of earlyonset infection in neonates.Methods. The study comprised 39 neonates, with a gestational age of 29 to 41 weeks, suspected of infection within 48 hours of life. Neutrophil surface expression of CD11b was quantified with flow cytometry and plasma IL-8 with an enzyme-linked immunosorbent assay. Both data were available from 35 of 39 neonates. Serum C-reactive protein was determined at initial evaluation and, later, on the basis of the clinical picture. Neonates were allocated retrospectively into 2 groups. In the sepsis group (N ‫؍‬ 22), 4 had culture-proven sepsis, and 14 had an antenatal risk factor for infection. In the possibleinfection group (N ‫؍‬ 13), each neonate had a noninfective disorder, but co-occurring infection remained a possibility. Twelve healthy term infants served as controls.Results. CD11b expression and IL-8 levels both increased in order of sepsis > possible infection > healthy. Sensitivity and specificity by the CD11b test for sepsis were equal, at 1.00, and those by the IL-8 test 0.91 and 1.00, respectively; 6 (17.1%) of the 35 neonates had CD11b and IL-8 below cutoff levels.Conclusions. Measuring neutrophil CD11b expression and circulating IL-8 provides a means to identify early-onset neonatal sepsis. The findings may be helpful in planning strategies to safely reduce the use of antimicrobials in neonates. Pediatrics 2001;108(1). URL: http:// www.pediatrics.org/cgi/content/full/108/1/e12; circulating IL-8, C-reactive protein, early-onset sepsis, neutrophil CD11b expression, newborn infant.ABBREVIATIONS. IL, interleukin; CRP, C-reactive protein; RFU, relative fluorescence unit; CI, confidence interval; ROC, receiveroperating characteristic curve. N eonatal sepsis is a life-threatening disease with an incidence of 1 to 10 per 1000 livebirths, and a mortality rate of 15% to 50%. 1 The clinical signs are nonspecific and indistinguishable from those caused by a variety of neonatal noninfective disorders, such as aspiration syndrome, maladaptation, and respiratory distress syndrome. It is therefore recommended for all neonates who develop these signs to start empirical antimicrobial therapy. 2,3 This clinical practice, however, renders many neonates unduly susceptible to side effects of antimicrobial agents, increases hospital costs, and promotes the development and spread in hospitals of resistant bacterial strains. 4 Therefore, markers are needed that reliably identify truly infected neonates.Invading microbes activate the host's innate immune cells, 5 including neutrophils and monocytes. Activated phagocytes produce inflammatory cytokines such as tumor necrosis factor-␣, interleukin (IL)-1␤, and IL-8. The release of these mediators into the circulation results in the development of systemic inflammation in adults 6 and children. 7 Systemic inflammation is considered to play an important role in the development of organ failure, 8 the major cause of mortality in sepsis. Elevated blood levels...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neutrophil CD11b Expression and Circulating Interleukin-8 as Diagnostic Markers for Early-Onset Neonatal Sepsis

et al. 2001

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“…Therefore, we examined the activation and functional status of the peritoneal neutrophils in day 7 burn-injured and sham mice. We used flow cytometry to measure cell-surface CD11b, a component of the Mac-1 complex, to judge neutrophil activation (23,24). In burn-injured mice, nearly all the peritoneal neutrophils expressed CD11b at baseline and had a higher expression density of this activation marker compared with shams (Fig.…”

Section: Injury Causes An Increase In Activated Peritoneal Neutrophilsmentioning

confidence: 99%

Injury Enhances Resistance to Escherichia coli Infection by Boosting Innate Immune System Function

Maung

Fujimi²,

MacConmara³

et al. 2008

The Journal of Immunology

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Major injury is widely thought to predispose the injured host to opportunistic infections. This idea is supported by animal studies showing that major injury causes reduced resistance to polymicrobial sepsis induced by cecal ligation and puncture. Although cecal ligation and puncture represents a clinically relevant sepsis model, we wanted to test whether injury might also lead to greater susceptibility to peritoneal infection caused by a single common pathogen, Escherichia coli. Contrary to our expectation, we show herein that the LD50 for sham-injured mice was 103 CFU of E. coli, whereas the LD50 for burn-injured mice was 50 × 103 CFU at 7 days postinjury. This injury-associated enhanced resistance was apparent as early as 1 day after injury, and maximal resistance was observed at days 7 and 14. We found that burn-injured mice had higher numbers of circulating neutrophils and monocytes than did sham mice before infection and that injured mice were able to recruit greater numbers of neutrophils to the site of infection. Moreover, the peritoneal neutrophils in burn-injured mice were more highly activated than neutrophils from sham mice as determined by Mac-1 expression, superoxide generation, and bactericidal activity. Our findings suggest that the enhanced innate immune response that develops following injury, although it is commonly accepted as the mediator of the detrimental systemic inflammatory response syndrome, may also, in some cases, benefit the injured host by boosting innate immune antimicrobial defenses.

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Beyond the Complete Blood Cell Count and C-Reactive Protein

Malik¹,

Hui²,

Pennie³

et al. 2003

Arch Pediatr Adolesc Med

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We found few methodologically rigorous studies of the accuracy of laboratory tests for the diagnosis of bacterial infection in newborns; in a significant proportion of studies, the accuracy of the tests could not be independently determined because of a lack of adequate data. There was marked heterogeneity in sample selection and cutoff levels for diagnosis of neonatal sepsis. A few tests showed promising accuracy, but there are insufficient data to support their confident use as clinical tools.

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Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection

Cited by 106 publications

References 57 publications

Neutrophil CD11b Expression and Circulating Interleukin-8 as Diagnostic Markers for Early-Onset Neonatal Sepsis

Neutrophil CD11b Expression and Circulating Interleukin-8 as Diagnostic Markers for Early-Onset Neonatal Sepsis

Injury Enhances Resistance to Escherichia coli Infection by Boosting Innate Immune System Function

Beyond the Complete Blood Cell Count and C-Reactive Protein

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