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Three Part Question

In [well appearing children suspected of meningococcal disease] can [procalcitonin] [reduce the need for empiric treatment]?

Clinical Scenario

A well appearing 4-year-old child presents to the emergency department with a fever and a non-blanching rash. There have recently been several missed cases of meningococcaemia at your institution. As a result, local practice has been changed to include giving empiric antibiotics to all suspected cases. You wonder whether a procalcitonin level would help you identify those patients who do and those who do not need antibiotics?

Search Strategy

PubMed/Medline 1946 to March 2013
EMBASE 1980 to March 2013
[(exp meningitis/) OR (meningococc$.ti,ab;)] AND [(exp procalcitonin/) OR (procalcitonin.ti,ab;)] Limit search to humans, English language and children.

Search Outcome

Eleven articles were found using Medline and 22 with the EMBASE interface. After abstract review and exclusion of duplicates, only two of these addressed directly the specific clinical question and age group.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Carrol et al, 2002 United Kingdom	108 Children referred to a MCD research fellow at one tertiary childrens’ hospital Children with microbiologically confirmed MCD were compared to those children initially thought to have MCD but subsequently ruled out	Prospective study	PCT < 2 to exclude meningococcal disease	Sensitivity 0.94 (0.85-0.97)	Potential selection bias No mention of blinding of test No follow-up
			PCT > 2 to diagnose meningococcal disease	Specificity 0.93 (0.82-0.98)
			PCT < 2 to exclude meningococcal disease	Negative likelihood ratio 0.07 (0.03-0.17)
			PCT > 2 to diagnose meningococcal disease	Positive likelihood ratio 13.7 (4.6-41.1)
Lepe et al. 2005 Spain	36 children aged 6 months to 16 years with fever above 38.5°C (axilla) presenting to one tertiary emergency department in Spain.	Prospective cohort study	PCT < 1 to exclude meningococcal disease	Sensitivity 1.0 (0.65-1.0)	Small cohort No blinding Large selection bias
			PCT > 1 to diagnose meningococcal disease	Specificity 0.65 (0.47-0.80)
			PCT < 1 to exclude meningococcal disease	Negative likelihood ratio 0.10 (0.006-1.426)
			PCT < 10 to exclude meningococcal disease	Sensitivity 1.0 (0.65-1.0)
			PCT >10 to diagnose meningococcal disease	Specificity 0.97 (0.83-0.99)
			PCT >10 to diagnose meningococcal disease	Positive likelihood ratio 18.7 (3.9-90.1)

Comment(s)

Procalcitonin, a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. MCD is a serious condition and the fear of missed cases has traditionally led to the widespread use of antibiotics and costly hospital admissions. There is also currently great variation in clinical practice for diagnosing this life-threatening disease including clinical presentation, inflammatory markers and blood cultures. A study by Carrol et al showed that procalcitonin was in fact a more sensitive and specific predictor of MCD than C-reactive protein and white cell cound in children presenting with fever and a rash. Lepe Jimenez et al demonstrated that findings of procalcitonin levels of less than 0.5 ng/ml and/or C-reactive protein levels of less than 49.95 ng/ml in children or teenagers with fever of less than 24 h of onset indicated a low probability of invasive MCD in epidemic situations.

Editor Comment

MCD, meningococcal disease; PCT, procalcitonin.

Clinical Bottom Line

The currently available evidence to use this marker to rule out MCD is based on studies with severe methodological flaws and therefore makes it difficult to have a clear clinical bottom line. More evidence is needed before the procalcitonin test alone can be considered to rule out safely the diagnosis of MCD.

References

1. Carrol ED, Newland P, Riordan FAI et al. Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash. Arch Dis Child 2002;86:282–5.
2. Lepe Jimenez JA, Vazquez Florido A, Ramos de Mora M, et al. [Utility of procalcitonin, C-reactive protein and leukocyte count in the detection of meningococcal disease during an epidemic cluster] An Pediatr (Barc). 2005;62:328–32.