C reactive protein and procalcitonin are helpful in diagnosis of serious bacterial infections in children

Article Outline

• Question
• Design
• Data Sources
• Study Selection and Assessment
• Outcomes
• Main Results
• Conclusions
• Commentary
• Copyright

Van den Bruel A, Thompson MJ, Haj-Hassan T, Stevens R, Moll H, Lakhanpaul M, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 2011;342:d3082.

Back to Article Outline

Question 

Among febrile children with suspected serious infections, how accurate are various laboratory tests?

Back to Article Outline

Design 

Systematic review.

Back to Article Outline

Data Sources 

Electronic databases, reference tracking, and consultation with experts.

Back to Article Outline

Study Selection and Assessment 

Studies were selected on six criteria: (1) design (studies of diagnostic accuracy or deriving prediction rules); (2) participants (otherwise healthy children and adolescents aged 1 month to 18 years); (3) setting (first contact ambulatory care); (4) outcome (serious infection); (5) features assessed (in first contact care); and (6) data reported (sufficient to construct a 2×2 table). Quality assessment was based on the quality assessment tool of diagnostic accuracy studies (QUADAS) criteria.

Back to Article Outline

Outcomes 

Diagnostic values (measured as sensitivity, specificity, and likelihood ratios) of C reactive protein (CRP), procalcitonin, and white blood cell count.

Back to Article Outline

Main Results 

14 studies were identified; none were of high methodologic quality and all were carried out in an emergency department or pediatric assessment unit. The prevalence of serious infections ranged from 4.5% to 29.3%. Tests were carried out for CRP (five studies), procalcitonin (three), erythrocyte sedimentation rate (one), interleukins (two), white blood cell count (seven), absolute neutrophil count (two), band count (three), and left shift (one). The tests providing the most diagnostic value were CRP and procalcitonin. Bivariate random effects meta-analysis (five studies, 1379 children) for CRP yielded a pooled positive likelihood ratio of 3.15 (95% CI, 2.67 to 3.71) and a pooled negative likelihood ratio of 0.33 (0.22 to 0.49). To rule in serious infection, cut-off levels of 2 ng/mL for procalcitonin (two studies, positive likelihood ratio 13.7, 7.4 to 25.3 and 3.6, 1.4 to 8.9) and 80 mg/L for CRP (one study, positive likelihood ratio 8.4, 5.1 to 14.1) are recommended; lower cut-off values of 0.5 ng/mL for procalcitonin or 20 mg/L for CRP are necessary to rule out serious infection. White blood cell indicators are less valuable than inflammatory markers for ruling in serious infection (positive likelihood ratio 0.87-2.43), and have no value for ruling out serious infection (negative likelihood ratio 0.61-1.14). The best performing clinical decision rule (recently validated in an independent dataset) combines testing for CRP, procalcitonin, and urinalysis and has a positive likelihood ratio of 4.92 (3.26 to 7.43) and a negative likelihood ratio of 0.07 (0.02 to 0.27).

Back to Article Outline

Conclusions 

Measuring inflammatory markers in an emergency department setting can be diagnostically useful, but clinicians should apply different cut-off values depending on whether they are trying to rule in or rule out serious infection. Measuring white blood cell count is less useful for ruling in serious infection and not useful for ruling out serious infection. More rigorous studies are needed, including studies in primary care, to assess the value of laboratory tests alongside clinical diagnostic measurements, including vital signs.

Back to Article Outline

Commentary 

Pediatricians have long sought diagnostic aids to predicting the presence of a severe infection in a child, particularly a young child, who presents with fever because the stakes may be high if a severe infection is not promptly identified and adequately treated. A cautionary tale from the results of this study is that the available literature to assess the value of laboratory tests as predictors of severe infection are of modest quality. Nevertheless, the results add to our current understanding and suggest that CRP (whose test result is usually available rapidly) and procalcitonin (whose test result may be delayed) levels may be useful in ruling in severe infection, and white blood cell count has little value at all. Of note, the data are best applied in the emergency department setting with higher probability of severe infection than in the primary care office setting with lower probability. A refreshing aspect of this study is the use of the test values to predict probability of infection, a more useful concept than considering the test values in absolute black and white terms. At the end of the day, the value of a laboratory test to predict severe infection relates to the prompt availability of the test result, the cost of the test, the added value of the test over other diagnostic modalities, and the setting (which affects the pre-test probability of a severe infection). Further, this study reaffirms that a laboratory test is a tool used to supplement a suspicion of severe infection based on the patient's history, the physical examination, and the clinical experience of the physician.