If I Have A 3-Month-Old Infant In The Office With Respiratory Symptoms And Negative Viral Testing, Should I Proceed With A Sepsis Evaluation?
The diagnosis of a respiratory viral infection cannot necessarily be “ruled out” based on laboratory evaluation, particularly with rapid testing. Traditionally, the isolation of respiratory viruses in tissue culture has been the “gold standard” for confirmation of an infection. However, these methods are time consuming and results are often not available for several days. For a 3-month-old infant, decisions for further evaluation are often based on more rapid methods in vogue today, including commercial rapid diagnostic tests, direct and indirect immunofluorescence antibody tests, and molecular diagnostic methods such as polymerase chain reaction (PCR). Each of these methods has its own sensitiv- ity, specificity, and positive and negative predictive value. Clinicians need to familiarize themselves with the performance characteristics of the test used in order to interpret the results. In general, in the office setting, sophisticated testing methods such as PCR are not likely to be available.
Commercially available rapid diagnostic tests vary in their reliability but are generally between 70% and 90% sensitive and more than 90% specific. One exception to this has been the H1N1 influenza virus rapid antigen test, which confers a sensitivity of 50%. This is not better than a flip of a coin, and as such, is not a good tool to determine whether or not a patient has this strain of influenza A virus. Additionally, both false-positive and false-negative results may be obtained, depending upon the time of year that the test is performed (whether or not the test is being performed in season), duration of the illness (the ability to identify the virus is inversely proportional to the length of time the patient has been ill), adequacy of the clinical sample (for some viruses it is important to obtain epithelial cells as well as mucus), and the type of virus for which the test is done (some viruses are more easily identified than others).
The decision to proceed with a sepsis evaluation should be made based upon the clinical presentation as well as the probability that the illness is associated with a respiratory viral illness. For example, in a patient who is febrile, irritable, somnolent, or feeding poorly, irrespective of the test results for viral etiologies, the clinician should consider pursuing a sepsis evaluation. In other patients who only have respiratory symptoms, the decision is more difficult. A few published studies suggest that the rates of concomitant serious bacterial infections (SBIs) in young infants with a positive respiratory syncytial virus (RSV) antigen test are low. The exception appears to be urinary tract infections (UTIs), which do sometimes occur in young infants who are RSV positive by rapid testing. The suggestion has therefore been made that while full sepsis evaluations may not be necessary in nontoxic-appearing infants with a positive RSV test result, it may be prudent to evaluate their urine for a clinically relevant UTI.
A number of studies with differing designs and populations of children have addressed the issue of interpreting rapid influenza tests in the context of the risk of con- comitant SBIs. A good review of these studies concludes that in the well-appearing, fully vaccinated febrile infant, given the declining rate of occult bacteremia, blood cultures may not be necessary in influenza-positive children. A more recent multicenter, prospective, cross-sectional study during 3 consecutive influenza seasons at 5 pediatric emergency departments confirms the low risk of SBI in influenza-positive infants (2.5%) compared to those who were influenza negative (13.3%). There was also a lower risk of UTIs (2.4%) in influenza-positive infants compared to those who tested negative (10.8%). Thus, it appears that in nontoxic-appearing infants who are influenza positive, a sepsis evaluation may not be necessary, but a urinalysis and culture may be useful.
Another aspect of the question posed that is not directly related to the test results or the patient’s clinical status, but has a bearing on the clinician’s decision, is his or her familiarity with the patient’s family. The physician may choose to observe a patient with respira- tory symptoms and negative viral testing, if he/she knows the family well and trusts the judgment of the caregivers. On the other hand, when the same patient is from a family that is new to the practice, or if the clinician is not confident about his or her ability to assess the patient, he or she may elect to pursue the sepsis evaluation.
There are further caveats to the conclusions in the paragraphs above. An association between influenza virus infections and bacterial infections has been recognized for nearly 100 years. It is important to understand, however, that these tend to be secondary and not concomitant infections. Several studies have determined that the rate of SBI coexisting with influenza disease was low. However, the diagnosis of influenza in these studies was often in older children and based on cell culture confirmation. Thus, there appears to be insufficient evidence to change current clinical practice algorithms for young infants with respiratory symptoms, particularly if they are febrile, based on office-based viral testing. Ultimately, the decision to initiate a sepsis evaluation must rest with the skilled clinician, who needs to weigh the clinical data and incorporate his or her knowledge of the performance characteris- tics of rapid viral testing before determining an appropriate course of action.
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Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics. 2004;113(6):1728-1734.
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