Reduction of Unnecessary Antibiotic Therapy in Newborn Infants Using Interleukin-8 and C-Reactive Protein as Markers of Bacterial Infections

Franz, Axel R.; Steinbach, Gerald; Kron, Martina; Pohlandt, Frank

doi:10.1542/peds.104.3.447

Cited by 158 publications

(129 citation statements)

References 39 publications

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“…Combining serum IL-8 with CRP improved the sensitivity from 83 to 93% without losing much specificity (7). Our data show a somewhat lower sensitivity (71%) for plasma IL-8.…”

Section: Discussionmentioning

confidence: 49%

“…Previous studies on the diagnostic value of plasma IL-8 in the prediction of EOBI reported this cytokine to be more sensitive but less specific than CRP at the onset of suspected infection (7,23,27). Combining serum IL-8 with CRP improved the sensitivity from 83 to 93% without losing much specificity (7).…”

Section: Discussionmentioning

confidence: 95%

“…As in various other studies (7,35,38), the majority of our EOBI group, therefore, consisted of patients defined as "clinically infected neonates" with one or more clinical symptoms, which may, however, be nonspecific, plus alterations in blood parameters, i.e. increased plasma IL-8 or CRP, leukocytosis, leukopenia, or increased I/T ratio.…”

Section: Lysed Blood Interleukin-8 In Neonatesmentioning

confidence: 99%

“…Plasma IL-8 is an appreciated, highly predictive, and easily accessible chemokine to detect EOBI (7). IL-8 secretion is not limited to infections (8 -10), yet it occurs within 1-3 h of endotoxin challenge (11).…”

mentioning

confidence: 99%

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Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

et al. 2004

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Plasma IL-8 is a diagnostic parameter of early-onset bacterial infection (EOBI) in neonates but has a short half-life. The detergent-lysed whole-blood (DLWB) IL-8 consists of both extracellular and cell-bound IL-8. The objective of this study was to investigate kinetics of plasma and DLWB IL-8 in healthy newborns and those with suspected EOBI and to test the hypothesis that determination of DLWB IL-8 results in higher sensitivity for EOBI detection. Sixty-one neonates with clinical and serologic signs of EOBI composed the study group; 188 neonates with risk factors but without EOBI served as control subjects. IL-8 concentrations were determined in plasma and DLWB. In the control group, DLWB IL-8 concentrations were 280-fold higher (9599 pg/mL; SD 4433) up to 24 h post partum than corresponding plasma levels (34.2 pg/mL; SD 18.1). The sensitivity of DLWB versus plasma IL-8 for EOBI was 0.97 versus 0.71 after 6 h and 0.70 versus 0.32 after 24 h. Corresponding values for specificity were 0.95 versus 0.90 after 6 h and 0.92 versus 0.99 after 24 h. After 24 h, the negative predictive value for DLWB versus plasma IL-8 was 0.80 versus 0.66. DLWB IL-8 showed a higher sensitivity for EOBI within 6 h after first clinical suspicion than plasma IL-8. It also remained elevated longer. Our results suggest that DLWB IL-8 results in a higher sensitivity for EOBI. Abbreviations CRP, C-reactive protein DLWB, detergent-lysed whole blood EOBI, early-onset bacterial infection I/T ratio, immature to total neutrophil ratio NPV, negative predictive value PPV, positive predictive value ROC, receiver operator characteristics Neonates are susceptible to infections (1). The differential diagnosis of early-onset bacterial infection (EOBI) therefore must always be present for the neonatologist, regardless of how minor, unexpected, or discrete the clinical symptoms. EOBI is usually defined as occurring up to 72 h after birth (2) and is associated with a high morbidity and mortality risk (1). The nonspecific clinical signs as well as the currently established biochemical and hematologic parameters have their diagnostic limitations (3,4) [reviewed in (5,6)].Plasma IL-8 is an appreciated, highly predictive, and easily accessible chemokine to detect EOBI (7). IL-8 secretion is not limited to infections (8 -10), yet it occurs within 1-3 h of endotoxin challenge (11). As with most cytokines, its plasma half-life is short (Ͻ4 h) (12,13). Circulating IL-8, which can be detected in plasma or serum via immunoassay, is immediately bound to two distinct high-affinity IL-8 receptors that are abundantly present on neutrophils before internalization and degradation (14,15). Therefore, plasma IL-8 reflects only a small portion of the total IL-8 blood pool, because the majority is cell associated (16 -18).Cell association is enhanced by chemokine binding, non-IL-8 -specific receptors. These have been identified on various cell types (19), including the Duffy antigen-related chemokine receptors (16), presented on erythrocytes. Duffy antigenrelated chemokine-li...

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“…Combining serum IL-8 with CRP improved the sensitivity from 83 to 93% without losing much specificity (7). Our data show a somewhat lower sensitivity (71%) for plasma IL-8.…”

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 95%

Section: Lysed Blood Interleukin-8 In Neonatesmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

et al. 2004

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“…Although these savings may seem relatively small from a budgetary perspective in comparison to (34) or a combination of IL-8 and C-reactive protein in neonates on first suspicion of a nosocomial bacterial infection (35). Despite these disparate diagnostic approaches, they show that more accurate and timely diagnostics are cost effective (with incremental costeffectiveness ratio of €3,107/qualityadjusted life years) and at times are cost saving.…”

Section: Discussionmentioning

confidence: 99%

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients

Tsalik

Hudson

et al. 2016

Annals ATS

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Rationale: Limitations in methods for the rapid diagnosis of hospitalacquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections.Objectives: We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. Methods:The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. Measurements and Main Results:In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved.Conclusions: Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a costeffectiveness framework for future test development.

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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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Reduction of Unnecessary Antibiotic Therapy in Newborn Infants Using Interleukin-8 and C-Reactive Protein as Markers of Bacterial Infections

Abstract: The combination of IL-8 and/or CRP is a reliable and early test for the diagnosis of NBI in newborn infants. Using the combination of IL-8 and/or CRP to restrict antibiotic therapy to truly infected infants reduces unnecessary antibiotic therapy and is cost-effective.

Cited by 158 publications

References 39 publications

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients

Beyond the Complete Blood Cell Count and C-Reactive Protein

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