An important step forward
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Procalcitonin assay best for detecting invasive bacterial infection

The procalcitonin assay is superior to C-reactive protein, neutrophil, and white blood cell measurements at identifying invasive bacterial infection in very young febrile infants, according to a study published Nov. 23 in JAMA Pediatrics.

Procalcitonin assays allow earlier detection of certain infections compared with other biomarker assays in older children, and a few small studies have hinted at their usefulness in infants, but to date no large prospective studies have assessed procalcitonin assays in the youngest infants. So investigators evaluated the diagnostic accuracy of procalcitonin and other biomarkers in a prospective study involving 2,047 febrile infants aged 7-91 days who presented to 15 pediatric emergency departments in France during a 30-month period.

Courtesy CDC / Melissa Brower
Group B streptococcus is a common cause of bacterial meningitis in newborns, according to the CDC.

“We did not include infants 6 days or younger because they are likely to have early-onset sepsis related to perinatal factors and because physiologic procalcitonin concentrations during the first [few] days of life are higher than thereafter,” said Dr. Karen Milcent of Hôpital Antoine Béclère, Clamart (France), and her associates.

Serum samples were collected from the infants at the initial clinical examination, but procalcitonin assays were not performed at that time. Attending physicians diagnosed the infants as having either bacterial or nonbacterial infections without knowing the procalcitonin results. Then procalcitonin tests were done retrospectively on frozen serum samples by lab personnel who were blinded to the infants’ clinical features. Thirteen (1.0%) infants had bacteremia and 8 (0.6%) had bacterial meningitis.

The procalcitonin assay was significantly more accurate at identifying invasive bacterial infections than was C-reactive protein level, absolute neutrophil count, or white blood cell count. At a threshold of 0.3 ng/mL or more, procalcitonin level had a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1. In addition, the procalcitonin assay was the most accurate in a subgroup analysis restricted to patients whose fever duration was less than 6 hours and another subgroup analysis restricted to patients younger than 1 month of age, the investigators said (JAMA Ped. 2015 Nov 23. doi:10.1001/jamapediatrics.2015.3210).

“Our results suggest that it may be possible to improve clinical practice for the treatment of young febrile infants” by combining procalcitonin assay results with a careful case history, a thorough physical examination, and other appropriate testing. Among other benefits, this approach offers the potential of avoiding lumbar punctures, they added.

These study findings “should encourage the development of decision-making rules that incorporate procalcitonin,” Dr. Milcent and her associates said.

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The findings by Milcent et al. are an important step forward in managing very young febrile infants, which remains a vexing and crucial problem in pediatrics.

A vital next step is to find alternatives to culture-based testing of blood, urine, and CSF. Genomic technologies that reliably detect molecular signatures in small amounts of biologic samples may be one such alternative. They may offer the additional benefit of identifying the pathogen and the host’s response to the presence of the pathogen.

Dr. Nathan Kuppermann is in the departments of emergency medicine and pediatrics at the University of California–Davis. Dr. Prashant Mahajan is in the departments of pediatrics and emergency medicine at Children’s Hospital of Michigan and Wayne State University, Detroit. They having no relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Milcent’s report (JAMA Ped. 2015 Nov 23. doi:10.1001/jamapediatrics.2015.3267).

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Body

The findings by Milcent et al. are an important step forward in managing very young febrile infants, which remains a vexing and crucial problem in pediatrics.

A vital next step is to find alternatives to culture-based testing of blood, urine, and CSF. Genomic technologies that reliably detect molecular signatures in small amounts of biologic samples may be one such alternative. They may offer the additional benefit of identifying the pathogen and the host’s response to the presence of the pathogen.

Dr. Nathan Kuppermann is in the departments of emergency medicine and pediatrics at the University of California–Davis. Dr. Prashant Mahajan is in the departments of pediatrics and emergency medicine at Children’s Hospital of Michigan and Wayne State University, Detroit. They having no relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Milcent’s report (JAMA Ped. 2015 Nov 23. doi:10.1001/jamapediatrics.2015.3267).

Body

The findings by Milcent et al. are an important step forward in managing very young febrile infants, which remains a vexing and crucial problem in pediatrics.

A vital next step is to find alternatives to culture-based testing of blood, urine, and CSF. Genomic technologies that reliably detect molecular signatures in small amounts of biologic samples may be one such alternative. They may offer the additional benefit of identifying the pathogen and the host’s response to the presence of the pathogen.

Dr. Nathan Kuppermann is in the departments of emergency medicine and pediatrics at the University of California–Davis. Dr. Prashant Mahajan is in the departments of pediatrics and emergency medicine at Children’s Hospital of Michigan and Wayne State University, Detroit. They having no relevant financial disclosures. They made these remarks in an editorial accompanying Dr. Milcent’s report (JAMA Ped. 2015 Nov 23. doi:10.1001/jamapediatrics.2015.3267).

Title
An important step forward
An important step forward

The procalcitonin assay is superior to C-reactive protein, neutrophil, and white blood cell measurements at identifying invasive bacterial infection in very young febrile infants, according to a study published Nov. 23 in JAMA Pediatrics.

Procalcitonin assays allow earlier detection of certain infections compared with other biomarker assays in older children, and a few small studies have hinted at their usefulness in infants, but to date no large prospective studies have assessed procalcitonin assays in the youngest infants. So investigators evaluated the diagnostic accuracy of procalcitonin and other biomarkers in a prospective study involving 2,047 febrile infants aged 7-91 days who presented to 15 pediatric emergency departments in France during a 30-month period.

Courtesy CDC / Melissa Brower
Group B streptococcus is a common cause of bacterial meningitis in newborns, according to the CDC.

“We did not include infants 6 days or younger because they are likely to have early-onset sepsis related to perinatal factors and because physiologic procalcitonin concentrations during the first [few] days of life are higher than thereafter,” said Dr. Karen Milcent of Hôpital Antoine Béclère, Clamart (France), and her associates.

Serum samples were collected from the infants at the initial clinical examination, but procalcitonin assays were not performed at that time. Attending physicians diagnosed the infants as having either bacterial or nonbacterial infections without knowing the procalcitonin results. Then procalcitonin tests were done retrospectively on frozen serum samples by lab personnel who were blinded to the infants’ clinical features. Thirteen (1.0%) infants had bacteremia and 8 (0.6%) had bacterial meningitis.

The procalcitonin assay was significantly more accurate at identifying invasive bacterial infections than was C-reactive protein level, absolute neutrophil count, or white blood cell count. At a threshold of 0.3 ng/mL or more, procalcitonin level had a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1. In addition, the procalcitonin assay was the most accurate in a subgroup analysis restricted to patients whose fever duration was less than 6 hours and another subgroup analysis restricted to patients younger than 1 month of age, the investigators said (JAMA Ped. 2015 Nov 23. doi:10.1001/jamapediatrics.2015.3210).

“Our results suggest that it may be possible to improve clinical practice for the treatment of young febrile infants” by combining procalcitonin assay results with a careful case history, a thorough physical examination, and other appropriate testing. Among other benefits, this approach offers the potential of avoiding lumbar punctures, they added.

These study findings “should encourage the development of decision-making rules that incorporate procalcitonin,” Dr. Milcent and her associates said.

The procalcitonin assay is superior to C-reactive protein, neutrophil, and white blood cell measurements at identifying invasive bacterial infection in very young febrile infants, according to a study published Nov. 23 in JAMA Pediatrics.

Procalcitonin assays allow earlier detection of certain infections compared with other biomarker assays in older children, and a few small studies have hinted at their usefulness in infants, but to date no large prospective studies have assessed procalcitonin assays in the youngest infants. So investigators evaluated the diagnostic accuracy of procalcitonin and other biomarkers in a prospective study involving 2,047 febrile infants aged 7-91 days who presented to 15 pediatric emergency departments in France during a 30-month period.

Courtesy CDC / Melissa Brower
Group B streptococcus is a common cause of bacterial meningitis in newborns, according to the CDC.

“We did not include infants 6 days or younger because they are likely to have early-onset sepsis related to perinatal factors and because physiologic procalcitonin concentrations during the first [few] days of life are higher than thereafter,” said Dr. Karen Milcent of Hôpital Antoine Béclère, Clamart (France), and her associates.

Serum samples were collected from the infants at the initial clinical examination, but procalcitonin assays were not performed at that time. Attending physicians diagnosed the infants as having either bacterial or nonbacterial infections without knowing the procalcitonin results. Then procalcitonin tests were done retrospectively on frozen serum samples by lab personnel who were blinded to the infants’ clinical features. Thirteen (1.0%) infants had bacteremia and 8 (0.6%) had bacterial meningitis.

The procalcitonin assay was significantly more accurate at identifying invasive bacterial infections than was C-reactive protein level, absolute neutrophil count, or white blood cell count. At a threshold of 0.3 ng/mL or more, procalcitonin level had a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1. In addition, the procalcitonin assay was the most accurate in a subgroup analysis restricted to patients whose fever duration was less than 6 hours and another subgroup analysis restricted to patients younger than 1 month of age, the investigators said (JAMA Ped. 2015 Nov 23. doi:10.1001/jamapediatrics.2015.3210).

“Our results suggest that it may be possible to improve clinical practice for the treatment of young febrile infants” by combining procalcitonin assay results with a careful case history, a thorough physical examination, and other appropriate testing. Among other benefits, this approach offers the potential of avoiding lumbar punctures, they added.

These study findings “should encourage the development of decision-making rules that incorporate procalcitonin,” Dr. Milcent and her associates said.

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Procalcitonin assay best for detecting invasive bacterial infection
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Key clinical point: The procalcitonin assay is superior to three other tests at detecting invasive bacterial infection in febrile infants aged 7-91 days.

Major finding: At a threshold of 0.3 ng/mL or more, procalcitonin level detected invasive bacterial infections with a sensitivity of 90%, a specificity of 78%, and a negative predictive value of 0.1.

Data source: A multicenter prospective cohort study involving 2,047 infants treated at pediatric EDs in France during a 30-month period.

Disclosures: The French Health Ministry funded the study. Dr. Milcent and her associates reported having no financial disclosures.