G-CSF and IL-8 for early diagnosis of sepsis in neonates and critically ill children – safety and cost effectiveness of a new laboratory prediction model: study protocol of a randomized controlled trial [ISRCTN91123847]

Abstract

Introduction Bacterial infection represents a serious risk in neonates and critically ill paediatric patients. Current clinical practice is characterized by frequent antibiotic treatment despite low incidence of true infection. However, some patients escape early diagnosis and progress to septic shock. Many new markers, including cytokines, have been suggested to improve decision making, but the clinical efficacy of these techniques remains uncertain. Therefore, we will test the clinical efficacy of a previously validated diagnostic strategy to reduce antibiotic usage and nosocomial infection related morbidity. Methods All patients admitted to the multidisciplinary neonatal and paediatric intensive care unit of a university children's hospital will be included. Patients will be allocated either to routine sepsis work up or to the intervention strategy with additional cytokine measurements. Physicians will be requested to estimate the pre-test probability of sepsis and pneumonia at initial suspicion. In the treatment arm, physicians will receive raw cytokine results, the likelihood ratio and the updated post-test probability. A high post-test probability will suggest that immediate initiation of antibiotic treatment is appropriate, whereas a low post-test probability will be supportive of watchful waiting or discontinuing prophylactic empirical therapy. Physicians may overrule the suggestions resulting from the post-test probability. Conclusion This trial will ascertain the clinical efficacy of introducing new diagnostic strategies consisting of pre-test probability estimate, novel laboratory markers, and computer-generated post-test probability in infectious disease work up in critically ill newborns and children.

Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

“…Despite substantial technological advances in the past decade, there is still a need for automated selective enrichment procedures for bacterial and fungal nucleic acids, blocking or elimination methods to eliminate excess human DNA, and use of viability markers to identify clinically relevant findings [22,91]. The target population most likely to benefit from the introduction of the rapid BSI diagnosis includes children (higher bacterial loads) [98] and patients with a high risk for infections with slow-growing, non-cultivable or intracellular bacteria or fungi, for example, neutropenic, transplant, critically ill and particularly antibiotic-pretreated patients.…”

Cytokine screening identifies NICU patients with Gram-negative bacteremia

“…In 10 of 226 cases, the blood culture was obtained because of abnormal HRC index alone. In the remaining cases, the major reason for blood culture was designated as gastrointestinal (67 cases), respiratory (67), CNS(29), skin (12), laboratory findings alone (16), and miscellaneous or not specified (25). …”

“…A number of studies in NICU patients have shown that measuring more than one biomarker has additional value over a single analyte in identifying patients with sepsis (4,16–20). Our study is the first, to our knowledge, to identify a cytokine combination with good diagnostic accuracy for GNB, likely due to our larger sample size.…”

Elevated Expression of IL-23/IL-17 Pathway–Related Mediators Correlates With Exacerbation of Pulmonary Inflammation During Polymicrobial Sepsis

“…In addition, instillation of G-CSF alone into rat lung has been shown to induce neutrophil recruitment, lung injury, and impaired pulmonary function (31). In fact, measurement of G-CSF levels in blood and tracheal aspirate has been proposed as an early diagnosis of sepsis in neonates and critically ill children (32). Surprisingly, levels of G-CSF remained high throughout the entire twenty hours of the study, whereas all the other cytokines and chemokines tested showed a biphasic expression pattern with an early increase in expression within the first 6 hours and a dramatic decrease thereafter.…”