Alessandra Panero

Reliability of Procalcitonin Concentrations for the Diagnosis of Sepsis in Critically Ill Neonates

We evaluated the reliability of serum concentrations of procalcitonin for the diagnosis of early- and late-onset sepsis in a neonatal intensive care unit (NICU) setting. Timed procalcitonin determinations were prospectively obtained during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group 1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection, group 2; and 17 with uncertain findings, group 3). After we established 95% hour-specific reference ranges for group 0, we performed multiple linear regression analyses to determine which maternal, intrapartum, and neonatal complications would affect normal procalcitonin values. Maternal diabetes was the only variable identified in group 2 patients that induced a significant deviation from procalcitonin reference ranges. Analyses of the pooled procalcitonin values obtained for group 1 patients over the 48-hour period after birth yielded a sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations in the detection of early-onset sepsis. In period 2, blood samples from 23 cases with systemic infections were analyzed for procalcitonin concentrations at the onset of signs of infection. The control group was formed by matching four uninfected NICU patients to each infected case. None of the procalcitonin values for the 92 controls overlapped those for the cases (sensitivity and specificity, 100%). Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.

C-Reactive Protein, Interleukin-6, and Procalcitonin in the Immediate Postnatal Period: Influence of Illness Severity, Risk Status, Antenatal and Perinatal Complications, and Infection

BACKGROUND Studies of the diagnostic accuracy of most laboratory tests for early-onset neonatal sepsis have yielded variable results. We investigated whether some of this variation might be attributable to differences in population baseline severity and risk status as well as to specific ante- and perinatal variables, independent of the presence of neonatal infection. METHODS The Score for Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP Perinatal Extension (SNAP-PE) used to define the combined physiologic and perinatal mortality risk. A total of 134 ill newborns (19 with early-onset infection and 115 with no infection) were available for simultaneous analysis of the association of SNAP, SNAP-PE, and maternal and perinatal variables with C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) concentrations at birth and at 24 and 48 h of life. RESULTS Early-onset neonatal infection was associated with significant increases in CRP, IL-6, and PCT concentrations at all three time points, independent of illness severity. However, among babies without infection, higher SNAP and SNAP-PE scores were associated with higher IL-6 concentrations at birth. Certain maternal or perinatal variables altered IL-6 and PCT values in the infected as well as in the uninfected neonates. However, if different cutoff points were used at any of the three neonatal ages, PCT sensitivity and specificity were greater than those of CRP or IL-6. CONCLUSIONS Illness severity and risk status are unlikely to interfere with the use of CRP and PCT for detection of early-onset neonatal sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for the diagnosis of early-onset neonatal infection requires specific cutoff values for each evaluation time point over the first 48 h of life.

Interleukin 6 in neonates with early and late onset infection.

OBJECTIVE To assess the utility of determining interleukin 6 (IL-6) concentrations for diagnosing early (< or = 48 h of life) and late onset infection in a neonatal intensive care setting. METHODS We measured serum IL-6 values in five groups of neonates on both postnatal Days 1 and 2 (early sampling): Group 1, patients with clinical and microbiologic evidence of early onset infection; Group 2, patients with negative body fluid cultures but strong evidence of infection (clinical septicemia); Group 3, patients without clinical and microbiologic evidence of infection; Group 4, patients in whom infection could be neither confirmed nor excluded; and Group 5, healthy neonates with a normal postnatal course. We also measured IL-6 values in older neonates who during their hospital stay developed systemic infection (late sampling). Three controls matched for duration of hospital stay and birth date were chosen for each patient. RESULTS On postnatal Day 1 IL-6 values were elevated in all four patient groups compared with those in healthy neonates (P < 0.05 by analysis of variance (ANOVA)). There were no significant differences found among patient groups. On postnatal Day 2 IL-6 concentrations were persistently elevated in Groups 1 and 2 compared with values from those in Group 3, Group 4 and healthy controls (P < 0.01). At this time no significant differences in IL-6 values were found between uninfected symptomatic patients (Group 3), patients with uncertain findings (Group 4) and healthy controls. IL-6 concentrations were significantly higher in patients with late onset infection at presentation than in the patient controls (P < 0.0001) and returned to low values in those who recovered from infection. CONCLUSIONS There are differences in the serum concentrations of IL-6 that can be helpful in detecting early and late onset infection in preterm and term neonates. During the first 48 h of life serial IL-6 determinations are necessary so as not to overdiagnose infection in a neonatal intensive care setting.

Polymorphonuclear leukocyte transfusion for the treatment of sepsis in the newborn infant

A therapeutic trial of transfusions with polymorphonuclear leukocyte concentrates was performed in newborn infants with bacterial sepsis proven by blood culture. With each transfusion, 20 ml/kg of a preparation obtained by continuous flow filtration leukapheresis, and containing 0.5 to 1 x 10(9) WBC, with less than 6% lymphocytes, was administered. Twenty newborn infants with sepsis received from 2 to 15 PMN transfusions. Results were compared with findings in 18 newborn infants with sepsis admitted during the trial period, and not treated because of unavailability of the PMN preparation (Group B). Infants with fulminant illness were excluded from both groups. Groups A and B were similar with respect to clinical characteristics and to etiology (in the majority cases a highly antibiotic-resistant Klebsiella). The mortality rate was significantly lower in Group A than in Group B in the whole series (10% vs 72%, P < 0.001), and also in the subgroups with birth weight equal or below 1,500 gm (10% vs 91%, P < 0.001). Major complications and associated conditions (i.e., necrotizing enterocolitis, meningitis, pneumonia, peritonitis, osteoarthritis, disseminated intravascular coagulation) were observed in 12 patients of Group B, and in only three infants of Group A. Untoward effects attributable to PMN transfusions were never observed. PMN transfusion was a highly effective therapeutic tool in our population of infected newborn infants.

Ureaplasma urealyticum and pulmonary outcome in a neonatal intensive care population.

OBJECTIVE To determine whether the presence of Ureaplasma urealyticum in the respiratory tracts of very low birth weight infants is associated with increased risk of pneumonia, radiographic evidence of severe bronchopulmonary dysplasia during the second or third week of life (precocious) and oxygen dependency at 36 weeks of corrected postnatal gestational age. METHODS From October, 1993, to January, 1996, all infants who met the following entry criteria were enrolled in the study: birth weights < or = 1500 g; admission to the NICU within 24 h after birth; evidence on admission of respiratory distress; and no prior antibiotic treatment. Infants were cultured for mycoplasmas, viruses, chlamydiae and aerobic and anaeroic bacteria. RESULTS Ninety-four critically ill newborns constituted our study cohort. Within 7 days of birth more infants with U. urealyticum infection showed radiographic features of pneumonia (53.1%, 25 of 47) than infants without U. urealyticum infection (21.2%, 10 of 47). Infants with U. urealyticum were more likely to have radiographic evidence of precocious bronchopulmonary dysplasia than those without this isolate (22.5%, 9 of 40 vs. 2.3%, 1 of 42). The relative risk of oxygen dependency at 36 weeks of corrected age in U. urealyticum-positive infants was 11.0 times that in U. urealyticum-negative infants (95% confidence interval, 1.6 to 75.5). Association of U. urealyticum and chronic lung disease at this age was not weakened after adjustments were made in a multivariate analysis for other significant risk factors including gestational age and presence of a patent ductus arteriosus. CONCLUSIONS Isolation of U. urealyticum from respiratory tracts is associated with radiographic changes compatible with pneumonia within 7 days of birth, precocious bronchopulmonary dysplasia and severe pulmonary outcome.

Hospital-acquired infection surveillance in a neonatal intensive care unit.

BACKGROUND Hospital-acquired infections (HAIs) represent an important cause of morbidity and mortality in neonatal intensive care units (NICUs). METHODS All neonates admitted for > 48 hours between January 2003 and December 2006 in the NICU of the teaching hospital Umberto I of Rome, Italy were considered. RESULTS Of the 575 neonates evaluated, 76 (13.2%) developed a total of 100 HAIs, including 36 bloodstream infections (BSIs), 33 pneumonias, 19 urinary tract infections, 8 conjunctivitis, and 4 onphalitis. There were 7.8 HAIs/1000 patient-days and 12.5 BSIs/1000 days of umbilical catheterization. Logistic analysis identified an association with mechanical ventilation (odds ratio [OR] = 3.05; 95% confidence interval [CI] = 1.75 to 5.31; P < .01) and birth weight <or= 1500 g (OR = 2.34; 95% CI = 1.36 to 4.03; P < .01). Thirty-five neonates (6.1%) died. Klebsiella pneumoniae (37.7%) and coagulase-negative staphylococci (28.6%) were the most frequently isolated microorganisms. Only 3 Candida spp determined BSIs (8.3%). BSI mortality was higher in infections with gram-negative pathogens (36.4%) than in infections with gram-positive pathogens (4.5%). CONCLUSIONS Although we found a low infection and mortality rate, attention should be directed toward antibiotic-resistant gram-negative pathogens.

Procalcitonin as a marker of nosocomial infections in the neonatal intensive care unit

ObjectiveTo determine accuracy of procalcitonin concentrations for diagnosing nosocomial infections in critically ill neonates.DesignCase-control study.SettingNeonatal intensive care unit of a teaching hospital.PatientsTwenty-three neonates with nosocomial infection. Four controls matched for duration of hospital stay and birth date were chosen for each case patient.Measurements and resultsPCT concentrations were measured by the LUMItest procalcitonin kit at onset of signs of infection and after recovery. Range of PCT concentrations (ng/ml) was 2.0 to 249.1 in case patients and 0.08 to 1.0 in controls (sensitivity and specificity, 100%). PCT values returned to normal (<1.0 ng/ml) by day 3 to 7 of appropriate antibiotic therapy.ConclusionsMeasurement of PCT concentrations may be useful for early diagnosis and monitoring of infectious complications in neonates during their stay in the neonatal intensive care unit.

Apparent Cure of a Newborn with Malignant Osteopetrosis Using Prednisone Therapy

A newborn girl with hemorrhagic purpura, suspected neonatal sepsis, and pale and dry skin was lethargic with remarkable hepatosplenomegaly, convergent strabismus, severe anemia, and elevated alkaline phosphatase activity. Radiographs showed a generalized increase in bone density, small medullary cavities, sclerosis of the skull and vertebrae, transverse wavy stripes of sclerotic bone in the metaphyses, and bone‐in‐bone appearance in phalanges of hands and feet. On this basis, she was diagnosed with malignant infantile osteopetrosis. On the first day of life, the infant was given a blood transfusion and vitamin K (1 mg intravenously [iv]). Corticosteroid therapy was started with prednisone (2 mg/kg per day). She showed marked improvement of symptoms. On the 26th day and 42nd day of life, she received additional blood transfusions. On the 49th day, the patient was discharged and corticosteroid therapy was continued at a regimen of 5 mg/day. Subsequent blood sample analyses revealed normal values for age. At 1 year of life, a bone marrow sample showed normal white and red cell lineages. X‐ray confirmed attenuation of the bone sclerosis; therefore, bone marrow transplantation (BMT) was not implemented. At the age of 1.5 years, prednisone therapy was discontinued gradually and withdrawn before the age of 2 years. Subsequent follow‐up showed normalization of all radiological and hematologic parameters. At present, the patient is 3 years old and appears healthy with apparently complete regression of the disease.

Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture

We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X‐ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydial infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term.

Chlamydia trachomatis‐associated respiratory disease in the very early neonatal period

Of 103 preterm neonates admitted consecutively to the neonatal intensive care unit soon after birth for respiratory distress, 8 were found to be Chlamydia trachomatis‐positive as early as within the first 24 h of life. All these patients required mechanical ventilation and supplemental oxygen. Six infants had evidence on chest radiographs of hyaline membrane disease, one of pneumonia, and one of slight bilateral parenchymal changes. Our results suggest that the presence of C. trachomatis in preterm infants with neonatal respiratory distress is probably not an infrequent event.