Diagnostic tests for bacterial infection from birth to 90 days---a systematic review

Fowlie, Peter W; Schmidt, Bernhard M.W.

doi:10.1136/fn.78.2.f92

Cited by 113 publications

(82 citation statements)

References 57 publications

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“…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)]. …”

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confidence: 99%

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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confidence: 99%

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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“…Conversely, low blood culture volumes, which are a major issue in premature neonates, and previous antimicrobial therapy may be responsible for false-negative results. [16][17][18] The test is not only imprecise but also time-consuming. Hence, with respect to both diagnostic and therapeutic strategy, clinicians often must make preliminary decisions based on largely nonspecific signs, especially in very low birth weight neonates.…”

Section: Resultsmentioning

confidence: 99%

Prediction Models for Neonatal Health Care–Associated Sepsis: A Meta-analysis

et al. 2015

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BACKGROUND AND OBJECTIVES: Blood culture is the gold standard to diagnose bloodstream infection but is usually time-consuming. Prediction models aim to facilitate early preliminary diagnosis and treatment. We systematically reviewed prediction models for health care-associated bloodstream infection (HABSI) in neonates, identified superior models, and pooled clinical predictors. Data sources: LibHub, PubMed, and Web of Science. METHODS:The studies included designed prediction models for laboratory-confirmed HABSI or sepsis. The target population was a consecutive series of neonates with suspicion of sepsis hospitalized for $48 hours. Clinical predictors had to be recorded at time of or before culturing. Methodologic quality of the studies was assessed. Data extracted included population characteristics, total suspected and laboratory-confirmed episodes and definition, clinical parameter definitions and odds ratios, and diagnostic accuracy parameters. RESULTS:The systematic search revealed 9 articles with 12 prediction models representing 1295 suspected and 434 laboratory-confirmed sepsis episodes. Models exhibit moderate-good methodologic quality, large pretest probability range, and insufficient diagnostic accuracy. Random effects meta-analysis showed that lethargy, pallor/mottling, total parenteral nutrition, lipid infusion, and postnatal corticosteroids were predictive for HABSI. Post hoc analysis with low-gestational-age neonates demonstrated that apnea/bradycardia, lethargy, pallor/mottling, and poor peripheral perfusion were predictive for HABSI. Limitations include clinical and statistical heterogeneity.CONCLUSIONS: Prediction models should be considered as guidance rather than an absolute indicator because they all have limited diagnostic accuracy. Lethargy and pallor and/or mottling for all neonates as well as apnea and/or bradycardia and poor peripheral perfusion for very low birth weight neonates are the most powerful clinical signs. However, the clinical context of the neonate should always be considered.

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“…Routine laboratory evaluation including neutrophil indices and C-reactive protein as potential markers of infection in newborn infants has shown limited value in the diagnosis of EOS sepsis. 3,16 Recent interest in the contribution of proinflammatory cytokines and acute phase reactants to diagnose newborn sepsis has also been disappointing. 4,5,17 Available studies to date are inconsistent with regard to sample size, methodology and test availability, which limits the clinician's confidence in applying these tests to practice.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, neither these clinical signs 1 nor currently available laboratory tests are reliable in the early detection of neonatal sepsis. [2][3][4][5] The blood culture has been the gold standard for the diagnosis of sepsis; however, technical pitfalls raise questions regarding blood culture reliability. 6,7 A justified concern regarding the ability to recover bacteria from the relatively small blood volumes collected for culture prompts clinicians to treat with antibiotics in spite of a negative blood culture (BC(À)).…”

Section: Introductionmentioning

confidence: 99%

Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can result in a decrease in use of antibiotics and total neonatal intensive care unit length of stay

et al. 2006

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Objective: To retrospectively determine if a negative 16S ribosomal RNA (rRNA) polymerase chain reaction (PCR) (PCR(À)) could lead to a decrease in the number of antibiotic doses and neonatal intensive care unit (NICU) length of stay (LOS) for infants admitted to the NICU for presumed early-onset sepsis (EOS) with negative blood culture results (BC(À)).Study design: Analysis included 419 infants, greater than 35 weeks gestational age, with PCR(À), BC(À) and LOS>48 h. Both the investigators and clinical care team were unaware of the PCR results. The actual number of antibiotic doses (AAD) administered was compared to an estimated number of antibiotics doses (EAD) that would have been given until PCR(À) results were available by 18 h. The number of antibiotic doses saved was calculated as (AADÀEAD). The actual NICU LOS in hours (aLOS) for a subset of infants who remained in the hospital primarily for antibiotic therapy was compared to an estimated LOS (eLOS) if infants with PCR(À) were discharged from the NICU when clinically stable. The number of hours saved was calculated as (aLOSÀeLOS).Results: Approximately eight antibiotic doses and 85 NICU hours per infant could be saved using PCR(À) results available at 18 h.Conclusions: Use of 16S rRNA PCR could decrease the number of antibiotics doses and NICU LOS for infants admitted for EOS. This may facilitate: (1) earlier NICU discharge; (2) parental satisfaction; and (3) decreased health care costs.

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Diagnostic tests for bacterial infection from birth to 90 days---a systematic review

Cited by 113 publications

References 57 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

Prediction Models for Neonatal Health Care–Associated Sepsis: A Meta-analysis

Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can result in a decrease in use of antibiotics and total neonatal intensive care unit length of stay

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