Neonatal sepsis: Procalcitonin for diagnosis and safe antibiotic guidance

brahms-pct-procalcitonin-neonatal-sepsisConfident diagnosis of neonatal sepsis with Procalcitonin (PCT) from the first day of life

In several studies Procalcitonin was found to be the best available marker for sepsis diagnosis in neonates Ref-1,2,3.

Neonatal sepsis is a leading cause of global mortality in children younger than 5 years  Ref-4. Proven early-onset sepsis has mortality rates as high as 30% in high-income countries and up to 60% in low-income countries Ref-5,6. Prompt diagnosis and treatment of neonatal early-onset sepsis are crucial to prevent severe morbidity and mortality. PCT enables detection of neonatal sepsis from the first day of life.

Procalcitonin shows a physiological elevation in newborns right after birth Ref-7,8, therefore, to use PCT in neonates during their first 48-72 hours of life, age-specific PCT reference values apply. 

 

pct-cutoff-values-newborns whiteFigure 1: Age adjusted B·R·A·H·M·S PCT cut-off values in newborns Ref-8

In healthy neonates, plasma Procalcitonin (PCT) concentrations increase gradually after birth, reaching peak values at about 24 hours of age and then decrease to normal values below 0.5 μg/L by 48-72 hours of age Ref-8.

Find out more about possible exceptions, where PCT can be elevated by non-bacterial causes:

Learn more >

 

Procalcitonin-guided antibiotic therapy and antibiotic reduction are safe in suspected early-onset neonatal sepsis

Early diagnosis of neonatal sepsis is vital to improve the outcome. In the absence of reliable infection markers during the first hours of life, antibiotic treatment in newborn infants with risk factors for infection is started early, exposing a considerable number of patients to unnecessary antibiotic therapy Ref-3. Culture-proven early-onset sepsis was found to be less than 0.1% albeit a much higher percentage (4.0 to 7.4%) of term to late-preterm neonates are given intravenous antibiotics within their first three days of life when sepsis is suspected Ref-8.
For term and near-term neonates with low likelihood of bacterial infection antibiotic treatment can be safely stopped based on two consecutive normal PCT values according to the age-specific B·R·A·H·M·S PCT reference values Ref-8 (Figure 1).

It has been shown in randomized controlled trials Ref-8,9, that by using such a procalcitonin-guided approach the antibiotic treatment duration could be shortened significantly (see Figure 2) without negative impact on the outcome.

pct-guided-treatment-suspected-neonatal-sepsisFigure 2: Impact on PCT-guided duration of antibiotic therapy in neonates with suspected early-onset sepsis Ref-8

 

The largest intervention study in neonates for shortening of antibiotic therapy

The recently published multicentric, multinational randomized controlled NeoPIns study shows a 15% reduced duration of antibiotic therapy guided by Procalcitonin (55 hrs vs. 65 hrs) and a shorter hospital stay in a large cohort of neonates with suspected early-onset sepsis. With 1710 neonates, NeoPIns is the largest randomized intervention study till date for shortening of antibiotic treatment in neonates Ref-8.

 

Learn more about Antibiotic Guidance with PCT >

 

Neonatal late-onset sepsis Ref-10

The B·R·A·H·M·S PCT cut-off level 0.5 μg/L proves useful for the diagnosis of late-onset infection in neonates. The sensitivity of Procalcitonin (PCT) for this diagnosis was 84.4%, specificity was 93.9%, positive predictive value was 82.6%, and negative predictive value was 94.6%  Ref-10.

 

pct-procalcitonin-likelihood-ratioFigure 3: Bayes nomogram for applying positive and negative likelihood ratios for PCT. Together, the data suggest that by analyzing PCT values, the likelihood of being infected increases from 25.6% to 84.4% when PCT is positive, and the likelihood of being non-infected decreases from 25.6% to 5.3% when the PCT level is below 0.5 µg/L. Ref-10

 

References

Ref-1: Vouloumanou E.K. et al., Intensive Care Med 2011;37 (5),May: 747-62.

Ref-2: Van Rossum A.M. et al., Lancet Infect Dis 2004;4 (10),Oct: 620-30.

Ref-3: Joram et al., Arch Dis Child Fetal Neonatal Ed 2006; 91: F65-F66

Ref-4: Collaborators GCM. Lancet 2016; 388: 1725–74.

Ref-5: Stoll BJ, Hansen NI, Sanchez PJ, et al. Pediatrics 2011; 127: 817–26.

Ref-6: Thaver D, Zaidi AK, Pediatr Infect Dis J 2009; 28(1 suppl): S3–9

Ref-7: Meisner M. Procalcitonin - Biochemistry and Clinical Diagnosis. Bremen 2010.

Ref-8: Stocker M. et al., Neonatology 2010; 97: 165-174

Ref-9: Stocker M. et al., Lancet 2017, 31444-7

Ref-10: Isidor et al., Scandinavian Journal of Infectious Diseases 2007; 39: 1063-1066.

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