May 2007 · Vol. 56, No. 5: 390-392
From the Family Physicians Inquiries Network
Can you differentiate bacterial from viral pediatric infections based on the CBC?
Uniformed Services University, Bethesda, Md
Battalion Surgeon USMC 3/6, Camp Lejeune, NC
Department of Preventive Medicine, Northwestern University, Evanston, Ill
No—the complete blood count (CBC) alone does not have adequate sensitivity or specificity to tell bacterial from viral infections (strength of recommendation [SOR]: B, cohort studies). When used in conjunction with other clinical parameters in validated decision-making algorithms, the CBC can help detect serious bacterial infections in pediatric patients with fever (SOR: B, cohort studies).
There’s no substitute for history, physical exam, and good judgment
Viral vs bacterial—often these are surrogate terms for minor vs serious illness. This review is a great lesson in likelihood ratios. Based on the low likelihood ratio, a CBC alone does not shift our suspicion greatly for serious bacterial infections in intermediate-risk patients; however, if you combine it with a clinical decision rule, it can greatly help decision-making, as evidenced by negative predictive values of 99% and above.
In contrast, we don’t need the CBC to tell us that an adult with the sniffles has a rhino/corona/whatevervirus, nor do we need it to tell us that a febrile, lethargic child with a petechial rash has a life-threatening bacteremia. If you enjoy the muck and the mess of primary care as much as I do, this inquiry should provide you with the validation that there’s no substitute for the history, physical exam, and judgment of a good clinician.
For acutely febrile patients, the presence of an elevated white blood cell (WBC) count with elevated band forms has dogmatically been thought of as a marker for bacterial infection.1 Current literature, however, does not support this.2
A CBC alone does not shift our suspicion greatly for serious bacterial infections in intermediate-risk patients
A retrospective study of 5353 infants ages 3 to 89 days presenting to the emergency department for evaluation of fever showed that 3 of 4 infants ultimately diagnosed with bacterial meningitis would have been missed if the WBC count alone were used to predict which infants need a lumbar puncture.3 A prospective study of 2492 children ages 3 to 24 months presenting to the emergency department with acute fever and an absolute WBC count >15,000/mm3 revealed that neither a polymorphonuclear count of >10,000/mm3 (>66% segmented forms) nor a band count of >500/mm3 was associated with an increased likelihood of occult bacterial infection.4 Other studies show that the WBC alone is poorly discriminatory for identifying either bacteremia or meningitis.5,6
To improve the diagnostic utility of the CBC, other studies have examined individual components of the white blood cell differential count (TABLE 1). In particular, the use of the absolute neutrophil count (ANC) has been proposed as a superior marker of serious bacterial infection.7 A review of 6579 outpatients aged 3 to 36 months presenting to the emergency department with temperatures of 39°C or higher showed an ANC of >10,000/mm3 as more predictive of occult pneumococcal bacteremia than an elevated WBC count (>15,000/mm3) alone.8 Another retrospective review of more than 10,000 patients aged 3 to 36 months presenting to the emergency department used logistic regression to identify predictors of bacteremia. In this study, ANC (>9500/mm3) and WBC (>14,300/mm3) were of equal sensitivity (75%) and specificity (75%) in identifying serious bacterial infection.9 Finally, the band count alone does not accurately predict serious bacterial infection.10
3 of 4 infants diagnosed with bacterial meningitis would have been missed if the WBC count alone was used
In summary, the CBC cannot be used in isolation to differentiate bacterial from viral illness. The CBC can, however, augment clinical data from the history and physical examination to predict the likelihood of serious bacterial illness. As a result, numerous diagnostic criteria, each incorporating elements of the CBC, have been developed in an attempt to accurately differentiate bacterial from viral illness in acutely febrile patients, most typically children (TABLE 2). These criteria differ by age of the patient, clinical testing recommendations, indications for antibiotic therapy, as well as WBC cutoffs.
WBC markers: How good are they at predicting serious bacterial infection?9,18,19
||LR (95% CI)
|White blood cell count
|Absolute neutrophil count
Clinical criteria for predicting serious bacterial infection in febrile children
||98.9% PV–in ruling out serious bacterial infection
||95% PV+ to identify serious bacterial infection
||100% PV–in ruling out serious bacterial infection
||1–3 mos Present to emergency dept. with fever ≥38.0°C
||29–56 days Present with fever ≥38.2°C
||Well-appearing Previously healthy No evidence of infection (skin, bone, joint, soft tissue or ear)
||Healthy appearing No ear, soft tissue, joint or bone infection on exam
|White blood cell count
||WBC 5–15,000/mm3 Bands ≤1,500/mm3
||Peripheral WBC ≤20,000/mm3
||WBC ≤15,000/mm3 Band-to-neutrophil ratio of ≤0.2
||≤10 WBC/hpf of centrifuged urine
||Urinalysis ≤10 WBC/hpf
||Urinalysis ≤10 WBC/hpf
||If diarrhea, ≤5 WBC/hpf of stool smear
||CSF WBC ≤10/hpf
||CSF WBC ≤8/hpf with negative gram stain If watery diarrhea, few or no WBC/hpf on stool smear
Recommendations from others
The American College of Emergency Physicians recommends considering antibiotic therapy for previously healthy, well-appearing children ages 3 to 36 months who present with a fever without a clinical source and a WBC count >15,000/mm3.3,14
In this age of vaccination, the rate of occult bacteremia in febrile children presenting without a source has fallen to 1% or less
The University of Cincinnati Evidence-Based Clinical Practice Guidelines for fever of uncertain source in children ages 2 to 36 months recommends obtaining a CBC for any child who is ill-appearing or at high risk for bacteremia (determined by the clinicians’ judgment). A WBC of ≥15,000/mm3 or ANC >10,000/mm3 provide support for antibiotic therapy.15 The 1993 American Academy of Pediatrics guidelines for fever ≥39°C without a source in children ages 3 months to 3 years recommends a CBC; if the WBC count ≥15,000/mm3, they recommend a blood culture and treatment with antibiotics pending culture results.3,16
It is important to note that in the age of Haemophilus influenza and Streptococcus pneumonia vaccination, the rate of occult bacteremia in febrile children presenting without a source has fallen from 3% to 10% to 1% or less.17 A lower prevalence reduces the utility of routine CBC or blood culture in the evaluation of immunized, febrile children. Parameters such as procalcitonin, interleukin-6, interleukin-8, interleukin-1 receptor antagonist and C-reactive protein show future promise as biochemical markers for identifying serious bacterial infections.18
- Wile MJ,
Manual differential cell counts help predict bacterial infection. A multivariate analysis. Am J Clin Pathol 2001;115:644–649.
- Seebach JD,
The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol 1997;107:582–591.
- Bonsu BK,
Utility of the peripheral blood white blood cell count for identifying sick young infants who need lumbar puncture. Ann Emerg Med 2003;41:206–214.
- Kramer MS,
Role of the complete blood count in detecting occult focal bacterial infection in the young febrile child. J Clin Epidemiol 1993;46:349–357.
- Brown L,
Does leucocytosis identify bacterial infections in febrile neonates presenting to the emergency department? Emerg Med J 2005;22:256–259.
- Garges HP,
Cotten CM, et al. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters? Pediatrics 2006;117:1094–1100.
- Gombos MM,
The absolute neutrophil count: is it the best indicator for occult bacteremia in infants? Am J Clin Pathol 1998;109:221–225.
- Kuppermann N,
Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med 1998;31:679–687.
- Isaacman DJ,
Predictors of bacteremia in febrile children 3 to 36 months of age. Pediatrics 2000;106:977–982.
- Cornbleet PJ.
Clinical utility of the band count. Clin Lab Med 2002;22:101–136.
- Dagan R,
Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis. J Pediatr 1985;107:855–860.
- Baskin MN,
Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr 1992;120:22–27.
- Baker MD,
The efficacy of routine outpatient management without antibiotics of fever in selected infants. Pediatrics 1999;103:627–631.
- American College of emergency Physicians. Clinical policy for children younger than three years presenting to the emergency department with fever. Ann Emerg Med 2003;42:530–545.
- Cincinnati Children’s Hospital Medical Center. Evidence-based clinical practice guideline for fever of uncertain source in children in 2 to 36 months of age. Cincinnati, Ohio: Cincinnati Children’s Hospital Medical Center; 2003.
- Baraff LJ,
Fleisher GR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Ann Emerg Med 1993;22:1198–1210.
- Stoll ML,
Incidence of occult bacteremia among highly febrile young children in the era of the pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med 2004;158:671–675.
- Pulliam PN,
C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics 2001;108:1275–1279.
- Pratt A,
Duration of fever and markers of serious bacterial infection in young febrile children. Pediatr Int 2007;49:31–35.
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