Serial cytokine profiles in shunt-related ventriculitis treated with intraventricular vancomycin.

BACKGROUND: A 1-month-old premature infant developed persistent shunt-related methicillin-resistant Staphylococcus aureus ventriculitis that was not responsive to parenteral therapy with vancomycin plus gentamicin (or rifampin). METHODS: The infant was treated by intraventricular administration of vancomycin (5 days: 10 mg/day). In addition to standard testing of the cerebrospinal fluid (CSF), tumor necrosis factor alpha, interleukin-8 and interleukin-6 were serially measured. RESULTS: Sterilization of the CSF was followed by a decline in the number of WBC and proinflammatory cytokines in the CSF. CONCLUSION: Intraventricular administration of antibiotics may be considered if ventriculitis is refractory to systemic antimicrobial therapy. Serial measurements of inflammatory cytokines in the CSF may provide an additional diagnostic tool to monitor the outcome of therapy.

Interleukin-6 and interleukin-8 are elevated in the cerebrospinal fluid of infants exposed to chorioamnionitis.

BACKGROUND: The clinical or histologic diagnosis of chorioamnionitis has been associated with an increased risk of neuropathology and adverse neurologic outcomes in premature and term infants. Inflammatory cytokines have been implicated in the pathogenesis of these processes. The objective of this study was to determine whether exposure to chorioamnionitis and fetal inflammatory syndrome is associated with elevated concentrations of inflammatory cytokines (TNF-alpha, IL-6, and IL-8) in the CSF of term and preterm infants. METHODS: Eighty-four mother/infant pairs were studied, 54 infants were premature. Twenty-eight showed signs of maternal (n = 14), or fetal (n = 14) inflammation based on placental pathology; mothers of 24 infants showed signs of clinical chorioamnionitis not confirmed by placental pathology and 32 infants were considered as 'controls' since they had only transient difficulty adjusting to extra-uterine life warranting evaluation for sepsis. The cytokine concentrations in the CSF were measured within 24 h of birth. RESULTS: When compared to the control group (IL-8 = 341 +/- 170 pg/ml and IL-6 = 7.4 +/- 1.8 pg/ml) significantly higher concentrations of IL-8 were detected in the CSF of infants exposed to clinical chorioamnionitis (1,854 +/- 878 pg/ml; p = 0.001) and maternal/fetal inflammation (1,754 +/- 787 pg/ml; p = 0.001) and of IL-6 in infants with maternal/fetal inflammation (47.6 +/- 45.1 pg/ml; p = 0.01). CONCLUSIONS: These results indicate that infants exposed to clinical chorioamnionitis, or inflammation in utero, experience at least a transient elevation in inflammatory cytokines in CSF.

Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis.

The first objective of this article was to determine the diagnostic accuracy of tumor necrosis factor-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) in differentiating infected from noninfected neonates during the first 24 hours of suspected sepsis and to compare them to the currently used laboratory parameters: C-reactive protein (CRP), immature-to-total neutrophil ratio, and leukocyte and platelet count. The secondary objective was to compare the cytokine levels in subpopulations of neonates. Seventy-five premature and 30 term infants were enrolled. Blood samples for the "currently used laboratory tests" and the cytokine levels were obtained at the first suspicion of sepsis ("0-hour") and 18 to 30 hours later ("24-hours"). Patients were classified as septic (48) or nonseptic (57). Thirty-two septic patients had positive blood cultures and 16 showed clinical signs of sepsis. Twenty septic patients had early-onset and 28 had late-onset sepsis. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each test. Receiver-operating characteristic curves were analyzed to determine the optimal thresholds. A combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL (sensitivity = 89%, specificity = 73%, PPV = 70%, NPV = 90%) was the best "0-hour" test, and CRP (sensitivity = 78%, specificity = 94%) was the best "24-hours" test. Lower IL-6 at 0-hour (p = 0.018) and IL-8 at 24 hours (p = 0.023) were detected among the patients infected with coagulase-negative staphylococci then with other bacteria. In conclusion, a combination of CRP + IL-6 provided additional diagnostic accuracy for differentiation between septic and nonseptic patients during the first 24 hours of suspected sepsis.

Comparison of recombinant granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor and placebo for treatment of septic preterm infants.

BACKGROUND: To reduce morbidity and mortality adjuvant cytokine therapy was administered to septic neonates with variable results. The objective of this case series was to compare the effectiveness of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) with that of placebo in correcting neutropenia induced by sepsis. METHODS: Symptomatic, septic premature neonates with or without a positive blood culture were eligible. Twenty-eight patients were randomized: 10 received rG-CSF (5 microg/kg/dose i.v. twice a day); 10 received rhuGM-CSF (4 microg/kg/dose i.v. twice a day) and 8 received placebo for a maximum of 7 days, or until an absolute neutrophil count (ANC) of 10,000 cells/mm was reached. RESULTS: A significant increase in the ANC above the baseline was present on Day 2 in the rG-CSF group (P = 0.015) and on Day 5 in the rhuGM-CSF (P = 0.002) and placebo (P = 0.027) groups. The ANC of the rG-CSF group was significantly above that in the rhuGM-CSF and placebo groups on Day 7 (P = 0.03). Mortality and neonatal intensive care unit morbidity was not significantly different between the groups. CONCLUSION: The neutrophil count in the rG-CSF-treated group increased significantly faster than that in the placebo or rhuGM-CSF group.