Malignant pertussis in infants: factors associated with mortality in a multicenter cohort study.

BACKGROUND: Malignant pertussis (MP) affects young infants and is characterized by respiratory distress, perpetual tachycardia and hyperleukocytosis up to 50 G/l, leading to multiple organ failure and death in 75% of cases. Leukodepletion may improve prognosis. A therapeutic strategy based on leukodepletion and extracorporeal life support (ECLS) according to different thresholds of leucocytes has been proposed by Rowlands and colleagues. We aimed at identifying factors associated with death and assess whether the respect of the Rowlands' strategy is associated with survival. METHODS: We reviewed all MP infants hospitalized in eight French pediatric intensive care units from January 2008 to November 2013. All infants younger than 3 months of age, admitted for respiratory distress with a diagnosis of pertussis and WBC count ≥ 50 G/l were recorded. Evolution of WBC was analyzed and an optimal threshold for WBC growth was obtained using the ROC-curve method. Clinical and biological characteristics of survivors and non-survivors were compared. Therapeutic management (leukodepletion and/or ECLS) was retrospectively assessed for compliance with Rowlands' algorithm (indication and timing of specific treatments). RESULTS: Twenty-three infants were included. Nine of 23 (40%) died: they presented more frequently cardiovascular failure (100% vs 36%, p = 0.003) and pulmonary hypertension (PHT; 100% vs 29%, p = 0.002) than survivors and the median [IQR] WBC growth was significantly faster among them (21.3 [9.7-28] G/l/day vs 5.9 [3.0-6.8] G/l/day, p = 0.007). WBC growth rate > 12 G/l/day and lymphocyte/neutrophil ratio < 1 were significantly associated with death (p = 0.001 and p = 0.003, respectively). Ten infants (43%) underwent leukodepletion, and seven (30%) underwent ECLS. Management following Rowlands' strategy was associated with survival (100% vs 0%; p < 0.001, relative risk of death = 0.18, 95%-CI [0.05-0.64]). CONCLUSIONS: A fast leukocyte growth and leukocytosis with neutrophil predominance during acute pertussis infection were associated with death. These findings should prompt clinicians to closely monitor white blood cells in order to early identify infants at risk of fatal outcome during the course of malignant pertussis. Such an early signal in infants at high risk of death would increase feasibility of compliant care to Rowlands' strategy, with the expectation of a better survival.

Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study.

Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared. Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates. Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12-24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably). Results: The study included 130 infants of median gestational age 28 weeks (range, 24-41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) for PCT were 59.3% (95% confidence interval [CI], 38.8-77.6%), 78.5% (95% CI, 67.8-86.9%), 48.5% (95% CI, 30.8-66.5%), 84.9% (95% CI, 74.6-92.2%), 2.7 (95% CI, 1.6-4.9), and 0.5 (95% CI, 0.3-0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% CI, 82.70-97.41%), PPV (72.22%; 95% CI, 46.52-90.30%) and LR+ (6.17, 95% CI, 2.67-28.44), but had low specificity (48.15%; 95% CI, 28.67-68.05%). Of all markers tested, the combination of IL-6 and CRPi had the highest sensitivity (78.12%; 95% CI, 60.03-90.72%), NPV (91.3%; 95% CI, 82.38-96.32%) and LR- (0.29; 95% CI, 0.12-0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (p = 0.055). Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.

A clinic-biological score for diagnosing early-onset neonatal infection in critically ill preterm infants.

OBJECTIVE: To identify the best combination of serum cytokines and clinical parameters to diagnose rapidly early-onset neonatal infection (EONI) in critically ill preterm infants. At birth, most critically ill neonates are receiving broad-spectrum antibiotics pending bacterial culture results, because distinguishing infected from noninfected infants at birth is difficult. DESIGN: Prospective study. SETTING: Neonatal intensive care unit in a tertiary care hospital. PATIENTS: Two hundred thirteen infants, born before 33 wks' gestation, admitted to the neonatal intensive care unit within 6 hrs of life with a presumptive diagnosis of EONI. INTERVENTION: A presumptive diagnosis of EONI was associated with a 300-µL blood sample to measure six cytokine (interleukin [IL]-1ß, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-α) concentrations, using the cytometric bead array technique. MEASUREMENTS AND MAIN RESULTS: Of the 213 infants included, 31 had a definite or possible EONI and 182 were not infected. Concentrations of IL-6, IL-8, and IL-10 were significantly increased in infected neonates, in comparison with infants without EONI. In contrast, IL-1ß, IL-12, and tumor necrosis factor-α concentrations were not. Logistic regression analyses were performed to construct multivariate predictive models that could distinguish infected from noninfected infants at birth. A clinical score was based on three parameters independently associated with EONI (i.e., interval of >12 hrs between the membranes rupture and delivery, prenatal maternal colonization and mechanical ventilation at birth). This score was compared with scores including clinical parameters and serum cytokines, alone or in combination. The best predictive model combined the three clinical parameters, IL-6 (positive threshold, 300 pg/mL) and IL-8 (positive threshold, 300 pg/mL) concentrations. CONCLUSION: A predictive model combining serum IL-6 and IL-8 measurements and selected clinical variables could distinguish infected from noninfected preterm infants at birth and should help the clinician in reducing or shortening the unnecessary use of antibiotics.

Efficacy of propranolol in hepatic infantile hemangiomas with diffuse neonatal hemangiomatosis.

We report the rapid and dramatic efficacy of propranolol in 8 infants with infantile hepatic hemangiomas. The degree of response varied from a significant improvement to a complete resolution of hepatic lesions. Heart failure and hypothyroidism resolved, and hepatomegaly decreased. No side-effects of the drug were noted.

Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene.

We report on a patient with a severe, rare neonatal form of non-dystrophic myotonia. The patient presented with facial dysmorphism, muscle hypertrophy, severe constipation, psychomotor delay, and frequent cold-induced episodes of myotonia and muscle weakness leading to severe hypoxia and loss of consciousness. Muscle biopsy was non-specific and electromyography revealed intense generalized myotonia. The myotonic episodes improved after introducing oral mexiletine and maintaining room temperature at 28 degrees C. The patient died at 20 months of age following a bronchopulmonary infection. A previously undescribed de novo heterozygous c.3891C > A change, which predicts p.N1297K in the SCN4A gene. Mutations within the voltage-gated sodium channel alpha-subunit gene (SCN4A) have been described in association with several phenotypes including paramyotonia congenita, hyperkalemic or hypokalemic periodic paralysis, and potassium-aggravated myotonias. The cold-sensitive episodes of stiffness followed by weakness suggested the diagnosis of channelopathy in our patient. However, her neonatal onset, the triggering of severe episodes by exposure to modest decreases in temperature, involvement of respiratory muscles with prolonged apnea, early-onset muscle hypertrophy, psychomotor retardation, and fatal outcome are evocative of a distinct clinical subtype. Our observation expands the phenotypic spectrum of sodium channelopathies.

A population-based observational study of restrictive guidelines for antibiotic therapy in early-onset neonatal infections.

BACKGROUND: The extensive use of broad-spectrum antibiotics has been associated with major changes in the spectrum of organisms involved in early-onset neonatal infection (EONI), their susceptibility to antibiotics, or both. Therefore, guidelines for a more rational use of antibiotics in neonates have been developed. We conducted a population-based observational study to assess the effectiveness and compliance with restrictive guidelines for the antibiotic therapy in EONI. METHODS: Neonates receiving antibiotics within 72 hours of life were identified prospectively by population-based surveillance in the 18 hospitals of Burgundy, between February 2002 and June 2003. They were treated in accordance with guidelines limiting the use of broad-spectrum antibiotics and shortening the treatment duration. Each neonate included was evaluated for 60 days after birth. An unfavorable outcome was defined as death related to EONI or late-onset infection. RESULTS: Of the 25,480 infants born during the study period, 1012 received antibiotics at birth. Of these 1012 infants, 39 were definitely infected (septicemia), 288 clinically infected and 685 not infected. The EONI cure rate was 96.8% without infectious relapse. Forty-five infants received a second course of antibiotic therapy. Birth weight (OR: 5.6; 95% CI: 2.2-14.1), mechanical ventilation (OR: 4.1; 95% CI: 1.3-13.1), central venous catheterization (OR: 16.1; 95% CI: 1.8-141.9), and antibiotic therapy duration (OR: 2.5; 95% CI: 1.1-5.5) were independently associated with late-onset infection. CONCLUSION: Reducing the antibiotic therapy duration does not increase the risk of infectious relapse and may decrease the incidence of late-onset infection.