Laboratory Studies
Blood and urine studies
Obtain a complete blood count (CBC). In the era of pneumococcal occult bacteremia, the likelihood of a positive blood culture result for pneumococci increased as the white blood cell (WBC) count increased. However, an elevated WBC count is no longer predictive of bacteremia when widespread pneumococcal conjugate vaccination is practiced.
Elevated band and other immature counts, toxic granulation, toxic vacuolation, Dohle bodies, and, particularly, low WBC counts are findings of particular concern (although they are quite nonspecific). Hemoconcentration may be present and can be helpful as a gauge of hydration status.
Measures of clotting function and coagulation parameters may be helpful. Disseminated intravascular coagulopathy (DIC), hypercoagulability, and other clotting dysfunctions may be seen in infants and children with systemic inflammatory response syndrome (SIRS).
Electrolyte level tests, renal and liver function tests, and other chemistry tests may have a role. Serum transaminase levels and other measures of liver dysfunction are often elevated in situations such as disseminated viral and anaerobic infections.
Etiology-specific serologies may be helpful, and urinalysis may have a role in clarifying the level of risk of urinary tract infection in infants and children. In addition, non–culture-based molecular modalities and other diagnostic methods are becoming increasingly important. [14]
The use of inflammatory markers and acute-phase reactants (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], interleukin [IL]–1b, IL-6, IL-8, tumor necrosis factor–alpha, leukotriene B4, procalcitonin [PCT]) in the diagnosis and management of pediatric sepsis is evolving. [15, 16]
A study aimed to determine biomarker phenotypes that differentiate children with sepsis who require intensive care from those who do not. The study concluded that in children ages 2-17 years, combining metabolomic and inflammatory protein mediator profiling early after presentation may differentiate children with sepsis requiring care in a pediatric intensive care unit from children with or without sepsis safely cared for outside a pediatric intensive care unit. The authors also add that these results may aid in making triage decisions, particularly in an ED without pediatric expertise. [17]
In a prospective study of 19 newborns with late-onset sepsis and 21 uninfected control subjects, presepsin (P-SEP), a trunked portion of soluble CD14, which is a diagnostic and prognostic marker of sepsis in adults, was found to be an accurate biomarker of late-onset sepsis in premature infants, as well as potentially useful in monitoring treatment response. [18, 19]
Median P-SEP values were higher in newborns with sepsis at study enrollment and over the course of the study (1295 ng/L in the late-onset sepsis group vs 562 ng/L in the control group). [19] The receiver operating characteristic curve of P-SEP values at baseline had an area under the curve of 0.972, suggesting that P-SEP is an accurate diagnostic test for late-onset sepsis. The best cutoff value was 885 ng/L, with 94% sensitivity, 100% specificity, a negative likelihood ratio of 0.05, and a positive likelihood ratio of infinity.
Culture of blood, urine, and CSF
Whenever possible, obtain a blood culture before starting antibiotics. The yield is clearly correlated to the volume of blood sampled. Culture of bone marrow may have a higher yield for certain pathogens (eg, Histoplasma capsulatum).
Obtain a urine culture unless, in an older child, a genitourinary source of infection can be reliably excluded.
Obtain a cerebrospinal fluid (CSF) culture before initiating antibiotic therapy if the child’s condition is stable but clinical evaluation cannot exclude central nervous system (CNS) infection. Many pathogens can be recovered from CSF cultures several hours after a dose of antibiotics; thus, a child whose condition is unstable should receive antibiotics and be stabilized before lumbar puncture. Once the child’s condition is stable, identification of CSF pleocytosis is helpful, even if prolonged antibiotic therapy may have rendered culture results negative.
Culture of skin lesions, eye drainage, throat, vagina, rectum, cellulitic areas, nasal secretions, sputum, tracheal aspirates, and stool may be helpful in the appropriate clinical context.
Viral cultures may have a role in certain contexts, although many viral infections are diagnosed via molecular methods or serologically.
Other Studies and Procedures
Obtain a chest radiograph; pneumonia, pleural effusions, adenopathy, and other conditions may be revealed. Pursue other imaging modalities (eg, computed tomography [CT] or magnetic resonance imaging [MRI]) as the clinical context dictates. Echocardiography may be indicated in certain clinical settings.
Lumbar puncture may be indicated for CSF evaluation. Sampling of other fluids or biopsy of various organs or tissues may be necessary.
Other Tests
A study by Balamuth et al reported that an electronic sepsis alert to detect severe sepsis had 86.2% sensitivity (95% confidence interval [CI] 82.0% to 89.5%), 99.1% specificity (95% CI 99.0% to 99.2%), 25.4% positive predictive value (95% CI 22.8% to 28.0%), and 100% negative predictive value (95% CI 99.9% to 100%). A positive electronic sepsis alert was defined as elevated pulse rate or hypotension, concern for infection, and either abnormal capillary refill, abnormal mental status, or high-risk condition. [20]
Scott et al reported that lactate levels greater than 36 mg/dL were associated with mortality in children suspected of sepsis but the test had low sensitivity at 20%. [21]
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Pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS).
