Procalcitonin, CRP May Predict Serious Bacterial Infection ...



Procalcitonin, CRP May Predict Serious Bacterial Infection in Febrile Infants CME

News Author: Laurie Barclay, MD

CME Author: Penny Murata, MD

Complete author affiliations and disclosures, and other CME information, are available at the end of this activity.

Release Date: February 9, 2009; Valid for credit through February 9, 2010

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Learning Objectives

Upon completion of this activity, participants will be able to:

1. Describe the predictive values of procalcitonin and C-reactive protein as markers for serious bacterial infection in febrile infants younger than 3 months.

2. Describe the predictive values of procalcitonin and C-reactive protein as markers for more invasive serious bacterial infection or fever of short duration in febrile infants younger than 3 months.

Authors and Disclosures

Laurie Barclay, MD

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Penny Murata, MD

Disclosure: Penny Murata, MD, has disclosed no relevant financial relationships.

Brande Nicole Martin

Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

February 9, 2009 — Procalcitonin (PCT) and C-reactive protein (CRP), along with currently used laboratory tests, may facilitate the treatment of infants younger than 3 months seen in emergency departments for fever of unknown origin, according to the results of a retrospective study reported in the January 21 Online First issue of Archives of Disease in Childhood.

"Although the majority of children present [with] minor infections, it is important to identify those with serious bacterial infection (SBI) in order to start antibiotic treatment early," write Izaskun Olaciregui, from Donostia Hospital in San Sebastian, Spain, and colleagues. "The Rochester scale includes a good general appearance in a previously healthy child, the absence of focal infection, and certain laboratory values (leucocyte count of 5000 - 15 000, ≤ 1500 band neutrophils, urinalysis with ≤ 10 leucocytes per high power field, and ≤ 5000 leucocytes per high power field in faeces in patients with diarrhoea) as indicators of good prognosis; the negative predictive value of this scale was 98.9% for SBI and 99.5% for bacteraemia....The objective of this study was to determine the ability of CRP and PCT to predict SBI in febrile infants under 3 months of age and to compare them with the Rochester criteria."

The study sample consisted of all infants younger than 3 months seen in the emergency department between January 2004 and December 2006 for a febrile syndrome with no evident cause. Clinical features, PCT, CRP, and leukocyte count were compared for their ability to differentiate SBI from non-SBI. The laboratory markers were evaluated with receiver operating characteristic curves and analyzed with multivariate logistic regression.

Among 347 patients studied, 23.63% had SBI. Patients with SBI had significantly higher mean PCT, CRP, and leukocyte and neutrophil counts vs patients with non-SBI. The other criteria evaluated did not differentiate SBI from non-SBI.

PCT and CRP were each better predictors of SBI vs leukocyte count, with an area under the receiver operating characteristic curve of 0.77 for PCT (95% confidence interval [CI], 0.72 - 0.81), 0.79 for CRP (95% CI, 0.75 - 0.84), and 0.67 for leukocyte count (95% CI, 0.63 - 0.73).

Among the 15 infants who had sepsis, bacteremia, bacterial meningitis, or other more invasive bacterial infections, the diagnostic value of PCT was higher than CRP (area under the receiver operating characteristic curve, 0.84; 95% CI, 0.79 - 0.88 vs 0.68; 95% CI, 0.63 - 0.73, respectively). Among infants in whom the duration of fever was less than 12 hours, the differences between PCT, CRP, and leukocyte count were statistically significant in both SBI and non-SBI groups, with increasing predictive value of PCT and decreasing value of CRP.

Limitations of this study include retrospective design, data from history and physical examination obtained from the clinical records, cultures not performed in a small percentage of the infants, and measurement of PCT with use of a semiquantitative method.

"PCT, CRP, and leucocyte count have intrinsic predictive value for SBI in febrile infants under 3 months of age," the study authors write. "The diagnostic value of PCT is greater than CRP for more invasive bacterial infections and for fever of short duration."

The study authors have disclosed no relevant financial relationships.

Arch Dis Child. Published online January 21, 2009.

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

1. Describe the predictive values of procalcitonin and C-reactive protein as markers for serious bacterial infection in febrile infants younger than 3 months.

2. Describe the predictive values of procalcitonin and C-reactive protein as markers for more invasive serious bacterial infection or fever of short duration in febrile infants younger than 3 months.

Clinical Context

The management of fever in infants younger than 3 months is important because of the absence of focus of infection and the risk for SBI. In the September 1994 issue of Pediatrics, Jaskiewitz and colleagues described the Rochester criteria, which have a negative predictive value of 98.9% for SBI and 99.5% for bacteremia: good general appearance, previously healthy, absence of focal infection, leukocyte count 5000 to 15,000 cells/µL, band neutrophils up to 1500 cells/µL, up to 10 leukocytes per high-power field in urinalysis, and up to 5000 leukocytes per high-power field in diarrheal stool.

This retrospective study assesses the predictive values of PCT and CRP as markers for SBI in febrile infants younger than 3 months.

Study Highlights

• Records were reviewed for 347 consecutive emergency department patients younger than 3 months with an elevated rectal temperature more than 38°C and no focus for infection by history and physical examination.

• Exclusion criteria were fever duration of more than 7 days, antibiotic use in the previous

48 hours, immunodeficiency, and lack of blood test.

• 151 patients were girls.

• Mean age was 47 days.

• Mean duration of fever at diagnosis was 15 hours.

• 82 (23.6%) had SBI: 69 cases of urinary tract infections (including 4 bacteremias), 5 cases of occult bacteremia, 4 cases of sepsis, 2 cases of cellulitis (1 bacteremia), 1 case of acute bacterial gastroenteritis with bacteremia, 1 case of pneumonia on chest radiograph, and no cases of bacterial meningitis.

• The subgroup with more invasive SBI consisted of 15 patients with bacteremia or sepsis.

• 265 patients in the non-SBI group included 74 with confirmed virus infections and 191 with probable virus infections (defined by negative results on cultures and spontaneous resolution).

• The SBI vs the non-SBI groups were similar in age, sex, prematurity, neonatal admission, duration of fever, rectal temperature, and good general state.

• The SBI vs the non-SBI groups had higher plasma leukocyte count (14,635 vs 10,084 cells/µL; P < .001), neutrophil count (7738 vs 4341 cells/µL; P < .001), CRP (59.3 vs 14.7 mg/L; P < .001), and more patients with PCT at least 0.5 ng/mL (63% vs 13%; P < .001).

• PCT and CRP vs leukocyte counts were stronger predictors for SBI (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72 - 0.81 vs 0.79; 95% CI, 0.75 - 0.84 vs 0.67; 95% CI, 0.63 - 0.73).

• In a previously healthy infant with good general state and negative urine dipstick result, CRP less than 30 mg/L, PCT less than 0.5 ng/mL, and leukocyte count between 5000 and 15,000 cells/µL were linked with a negative predictive value of 96% for SBI and 100% for sepsis and bacteremia.

• In infants with more invasive bacterial infections, the diagnostic value was higher for a PCT cutoff value of 0.5 ng/mL vs a CRP cutoff value of 30 mg/L (area under the receiver operating characteristic curve, 0.84; 95% CI, 0.79 - 0.88 vs 0.68; 95% CI, 0.63 - 0.73).

• Multivariate logistic regression showed that leukocyte count, CRP, and PCT had a predictive value for SBI (odds ratio, 1.1 vs 6.3 vs 6.6, respectively).

• In 258 infants with fever for less than 12 hours, the predictive value for SBI remained significant for leukocyte count, decreased slightly for CRP, and increased for PCT (odds ratio, 1.1 vs 5.6 vs 7.9, respectively).

• Limitations of the study included retrospective design and use of semiquantitative PCT measurement.

Pearls for Practice

• In febrile infants younger than 3 months, higher PCT, CRP, leukocyte, and neutrophil values are linked with SBI. A CRP less than 30 mg/L, PCT less than 0.5 ng/mL, and leukocytes between 5000 and 15,000 cells/µL in a previously healthy infant in good general state and negative results on urine dipstick are linked with a negative predictive value of 96% for SBI.

• In febrile infants younger than 3 months, PCT has greater diagnostic value than CRP, with more invasive bacterial infections or fever up to 12 hours.

Principio del formulario

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|In a 2-month-old febrile infant, which of the following laboratory values is most likely to be associated with SBI? |

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|PCT of 0.25 ng/mL |

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|PCT of 2.5 ng/mL |

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|CRP of 0.25 mg/L |

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|CRP of 2.5 mg/L |

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|A 10-week-old infant has an elevated rectal temperature of 100.6°F. Laboratory evaluation includes PCT and CRP values. PCT |

|would most likely have greater diagnostic value than CRP if the fever duration is which of the following? |

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|6 hours |

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|16 hours |

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|26 hours |

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|36 hours |

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Final del formulario

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Target Audience

This article is intended for primary care clinicians, pediatric infectious disease specialists, emergency medicine specialists, and other specialists who provide care to febrile infants younger than 3 months.

Goal

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

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Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Medscape Medical News has been reviewed and is acceptable for up to 350 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins 09/01/08. Term of approval is for 1 year from this date. This activity is approved for 0.25 Prescribed credits. Credit may be claimed for 1 year from the date of this activity.

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Authors and Disclosures

As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

News Author

Laurie Barclay, MD

is a freelance reviewer and writer for Medscape.

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Author

Penny Murata, MD

is a freelancer for Medscape.

Disclosure: Penny Murata, MD, has disclosed no relevant financial relationships.

Brande Nicole Martin

is the News CME editor for Medscape Medical News.

Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

Medscape Medical News 2009. ©2009 Medscape

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