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Rapid quantitative procalcitonin measurement is useful in ruling out nosocomial infections in neonates admitted to intensive care units, according to a report in the Archives of Disease in Childhood: Fetal and Neonatal Edition for September.

"In a population of hospitalized term and preterm newborn infants...procalcitonin had an excellent negative predictive value for a cut-off value of 0.6 ng/mL, which suggests that procalcitonin measurement could be used to rule out late-onset sepsis," Dr. Aurelien Jacquot, from Hopital Arnaud de Villeneuve, Montpellier, France, and colleagues note.

Late-onset sepsis, a common finding in neonatal intensive care units, is associated with both morbidity and mortality. Diagnosing the problem, however, can be difficult without specific clinical signs or biological markers in the first phase of infection, the researchers note.

Among the markers of inflammation, procalcitonin is more specific for bacterial infections than is C-reactive protein, the authors note. Monitoring of serum procalcitonin levels, they add, may help guide management of nosocomial infections. Moreover, a new automated and rapid quantitative test for procalcitonin is now available.

In a prospective study involving all newborns admitted to a neonatal ICU with a clinical suspicion of infection, rapid quantitative procalcitonin testing was done on blood samples taken for C-reactive protein measurement.

All standard test parameters, including negative and positive predictive values as well as sensitivity and specificity, were calculated. Logistic regression analysis was used to identify the optimal cut-off value needed to achieve a negative predictive value for procalcitonin that was 15% or higher above that of C-reactive protein.

The study featured 73 newborn infants, seen from June 2005 to May 2006, with a median gestational age of 28 weeks and birth weight of 995 g, the researchers report.

Overall, 30 infants (41%) were found to have infections. The optimal procalcitonin cut-off value was 0.6 ng/mL, which yielded a negative predictive value of 100%. The sensitivity, specificity, and positive predictive value using this cut-off were 100%, 65%, and 67%, respectively.

"To our knowledge, this is the first study to evaluate the rapid, automated and quantitative measurement of procalcitonin in newborn infants," the researchers comment.

"Our results suggest that rapid, automated procalcitonin measurement could help to rule out late-onset sepsis in newborn infants in intensive care, but they still need to be confirmed by larger prospective studies," Dr. Jacquot's team states. "These trials could validate our potential cut-off value and determine if a decision strategy taking into account procalcitonin concentration could help to reduce unnecessary antibiotic therapy in neonatal intensive care units.

"Arch Dis Child Fetal Neonatal Ed.. 2009;94:F345-F348.

Abstract

Late-onset sepsis leads to increased newborn mortality and morbidity rates. Its incidence in very-low-birth-weight neonates ranges from 15% to 30%. It usually results from coagulase-negative staphylococcus infections. Diagnosis is difficult at times because of the absence of clinical signs and biologic markers specific to the initial phase of the infection. With every suspected infection, broad-spectrum antibiotics are initiated and possibly exposing newborns to unnecessary therapy. A biological marker with excellent negative predictive value is needed in this situation. It has been proposed that serum procalcitonin monitoring may help clinicians to manage nosocomial infections in neonates.

The aim of this study was to investigate the diagnostic value of a new, rapid method to measure procalcitonin and to determine the best cutoff value.

Study Highlights

In this monocentric, prospective study, all newborn infants with clinical suspicion of infection, whether hemodynamic, respiratory, or intestinal, were enrolled from a neonatal intensive unit at Croix-Rousse Hospital, Lyon, France.

• Newborn infants receiving antibiotic treatment, those with severe congenital malformation or requiring neonatal surgery, or those diagnosed with necrotizing enterocolitis were excluded.
• Rapid, automated procalcitonin measurements were performed on blood samples obtained for C-reactive protein measurement.
• For all newborn infants, broad-spectrum antibiotic therapy, specifically vancomycin and amikacin, were started immediately after the blood sampling, per neonatal intensive care unit protocol.
• Negative and positive predictive values, sensitivity, and specificity were calculated.
• Logistic regression analysis determined the best cutoff value to obtain a negative predictive value of procalcitonin that was at least 15% more vs C-reactive protein.
• The Vermont Oxford Network's definition of coagulase-negative staphylococcus septicemia was used. It required the presence of a central catheter, clinical signs of sepsis, 2 positive blood culture results for coagulase-negative staphylococcus, and intravenous antibacterial therapy for at least 5 days.
• Between June 2005 and May 2006, a total of 73 newborn infants with a median (25th - 75th quartile) gestational age of 28 weeks (range, 26 - 30 weeks) and a birth weight of 995 g (range, 720 - 1350 g) were included.
• 30 infants (41%) were infected. Of those infected, 26 (87%) presented with septicemia, 3 (10%) presented with meningitis, and 1 (3%) presented with lower respiratory tract infection.
• Coagulase-negative staphylococcus caused late-onset sepsis in 19 cases (63%); additional organisms included Staphylococcus aureus, group B streptococci, Escherichia coli, and Pseudomonas aeruginosa.
• Procalcitonin was significantly higher in the infected group vs the noninfected group: 2.3 ng/mL (range, 1 - 7.8 ng/mL) vs 0.4 ng/mL (range, 0.3 - 1.1 ng/mL; P = .0084).
• The best procalcitonin cutoff value was 0.6 ng/mL, which provided a negative predictive value of 100%.
• The sensitivity, specificity, and positive predictive value were 100%, 65%, and 67%, respectively, for procalcitonin at the 0.6-ng/mL cutoff value.

Clinical Implications

• In late-onset sepsis, its cause is often the result of coagulase-negative staphylococcus.
• Rapid measurement of procalcitonin could help to rule out nosocomial infection in newborn infants, with a procalcitonin value of 0.6 ng/mL.

Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis

Background: Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success.

Objective: To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis.

Methods: This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children's Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age 34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48-72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values.

Results: 121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics 72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12-0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events.

Conclusion: Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.
(Martin Stocker, Matteo Fontana,et al. Neonatology 2010; 97:165-174)