Robert S. Baltimore, MD

Rapid molecular analysis of blood may soon replace standard cultures in the management of young febrile infants.

One of the major issues in acute care pediatrics is management of febrile infants, especially those aged >3 months. Although most such episodes are not caused by serious bacterial infection (SBI), the rapidity with which life-threatening infections can develop in infants who appear only mildly ill often results in unnecessary hospitalization and use of broad-spectrum intravenous antibiotics.

Investigators have attempted to develop clinical criteria that — used in combination with laboratory screening tests — can define a group of infants who are unlikely to have SBI and thus do not require hospitalization or empirical antibiotics, but no criteria or clinical prediction rules have been sufficiently definitive to rule out SBI. False-positive results with blood and cerebrospinal fluid cultures and the ensuing need for additional, unnecessary tests and possible hospitalization may outweigh the possible benefits of these measures.

A solution to this problem requires tests that can positively recognize patterns of bacterial disease with high sensitivity and few false-positives. Mahajan and colleagues propose that molecular assays in current development have such characteristics. Although polymerase chain reaction has become the standard for detecting many viruses, it has not yet proven sufficiently sensitive for detection of bacteria in the blood. However, microarray analysis of the RNA of blood leukocytes can reveal distinct host responses to various classes of pathogens and allow differentiation among them (e.g., bacteria vs. viruses, gram-positive vs. gram-negative bacteria) without requiring pre-incubation or culture. Based on promising small studies that have already been published, the authors call for prospective evaluation of this approach.

CITATION(S):

Mahajan P et al. The future possibilities of diagnostic testing for the evaluation of febrile infants. JAMA Pediatr 2013 Aug 19; [e-pub ahead of print].