Case and Commentary
Dec 2004

A Fever of Unknown Source, Commentary 2

Robert H. Pantell, MD
Virtual Mentor. 2004;6(12):531-533. doi: 10.1001/virtualmentor.2004.6.12.ccas1-0412.


Mr. and Mrs. Kendall were quite excited about the newest addition to their family, 2-month-old Janna. But they were anxious on this trip to the doctor. Janna had developed a fever in the middle of the night, and the Kendalls decided to take her to the emergency room. Dr. Stinton, the ER physician on service, heard of the Kendalls' story and decided she'd better see their daughter straight away.

Upon questioning, Dr. Stinton learned that Mrs. Kendall's pregnancy with Janna was perfectly normal, as was her delivery at just over 38 weeks. In fact, until last night, the Kendalls had little reason to be concerned about Janna's health. As they reported, she'd passed all her doctor's visits with flying colors and had begun immunizations according to schedule. In other words, she was overall a healthy infant.

Last night, however, they awoke to cries unlike those they had heard before and ran in to check on Janna. She had no interest in being fed and seemed warm to her mother. She had been irritable throughout the day and less interested in nursing. Mrs. Kendall took Janna's temperature twice rectally, and both times it read 38.3° C. That's when they bundled her up and went to the ER.

On physical exam, Janna was alert and active in her mother's arms, but appeared ill. Her temperature registered 38.4° C. The physical was normal, revealing no obvious foci of infection. A complete blood count in the ER uncovered a slightly elevated white blood cell count (15.5 x 109 cells / Liter) but no other abnormalities. On the basis of these findings, Janna was admitted to the hospital for fever of unknown source; her workup included urinalysis, urine culture, chest radiography, blood cultures, and lumbar puncture. In lieu of lab results, antibiotics were started.

Distressed by the invasiveness of the tests (which lasted well into the early morning hours) and the hospital admission, the Kendalls asked for more information about the likelihood of a serious illness. Dr. Stinton responded that it was hard to say. "The information is quite complex, and we don't want to confuse you. Let's not take any chances." Willing to do whatever it took for Janna to be well, they agreed.

After Janna reached the hospital ward, Mr. Alstadt, a medical student on his clinical clerkship began learning Janna's story through the family's account and ER notes. He diligently prepared for presenting his new patient on rounds later that day.

When the attending asked Mr. Alstadt the reason for Janna's admission, Mr. Alstadt recalled the story and was poised with several sets of clinical guidelines and algorithms from various sources that he had researched overnight.1,2 He quoted beautifully from them, and most of them seemed to support admitting Janna for a full sepsis workup.

The attending physician was not convinced. "Really? Who recommends a full sepsis workup for a moderately ill, 2-month-old infant likely to have reliable follow-up with her parents? In my clinical judgment, this patient should have been sent home last night, maybe after taking a blood culture, but definitely without a lumbar puncture. I think medical school should spend less time teaching you those guidelines and give you more time to really see patients. That's where you learn to practice medicine. Well, she's here now. Let's go see her."

The team walked to Janna's room, where they found an infant whose temperature was now 37.3° C, sleeping pleasantly. Her parents appeared tired, but relieved.

The attending physician glanced at Mr. Alstadt and smiled.

Commentary 2

The optimal management of fever in young infants has been a hot topic in pediatrics for over 30 years. Physicians have always used clinical judgment in deciding on the best strategy to deal with a patient's problem. Infants, however, cannot tell their own stories, and clinical signs and physical findings are often less reliable than in older babies and children. Furthermore, serious infections may develop and progress more rapidly in young infants. In the 1970s a re-emergence of group B beta streptococcal disease in newborns, as well as late onset group B streptococcal infections in early infancy with accompanying reports of considerable morbidity and mortality, concerned physicians. Reports emerged that clinical judgment was often inaccurate in identifying whether febrile infants had a minor respiratory infection or sepsis.1 Consequently many academic medical centers developed policies to perform a complete sepsis work-up on all febrile infants. Some institutions limited this policy to infants less than a month old while others included infants as old as 3 months. In addition to obtaining blood for CBC and culture, clinicians were required to obtain urine by catheterization for analysis and culture. Lumbar punctures were required to analyze and culture cerebrospinal fluid. All infants were then placed on appropriate intravenous antibiotics and hospitalized for 2 to 3 days until culture results were known.

These policies were designed to minimize the likelihood that an untreated occult infection in a febrile infant would progress and harm the child. Unfortunately the procedures, antibiotics, and hospital experiences also carry their own potential for harm. The iatrogenic consequences of this policy of hospitalizing febrile infants were highlighted in a 1983 report.2 Furthermore, all antibiotics have adverse consequences; lumbar punctures have a very small but documented morbidity and mortality, and hospitals are sources of nosocomial infections and medication errors. Finally, the psychological and financial costs of hospitalizing young infants are considerable.

Despite many published reports advocating for such policies, implementation was far from universal, particularly by practicing pediatricians. Most recommendations came from institutions caring for large populations of poor children living in the inner city and utilizing emergency rooms. Pediatricians wondered how relevant these studies were to their individual populations of patients. Also, one study suggested that if these guidelines were strictly followed, between 5 percent and 10 percent of infants less than 3 months old seen in a community practice would be hospitalized.3

In the late 1990s, the Pediatric Research in Office Settings (PROS) network of the American Academy of Pediatrics sought to clarify the optimal strategy for managing febrile infants. This nationwide network of more than 1000 clinicians was able to study a broad cross-section of infants with a diverse geographic, economic, and ethnic mix. In PROS' Febrile Infant Study, 573 clinicians recorded their usual practice in caring for 3006 episodes of fever in infants less than 3 months old along with clinical outcomes.4

This study differed from most previous studies by having infants from community practices. Unlike many patients seen in emergency rooms, these infants/families are often well known by their clinicians. In primary care practice it is also customary to follow such patients closely. In this study most infants had an additional visit and phone follow up. Only about 40 percent of the clinicians followed the published policies. (Note: Although there are common references to fever "guidelines," and many respected clinicians and researchers have published their versions of optimal care, no professional society or governmental group has issued "guidelines" on the management of febrile infants). The PROS study documented 54 cases of bacteremia and 14 cases of bacterial meningitis (5 were simultaneously bacteremic) out of the more than 3000 fever episodes. These were considered the most serious illnesses, ie, those for which a delay in diagnosis and treatment could have serious consequences for infants. Of the 63 infants with these diagnoses, 61 were treated with appropriate antibiotics at the initial visit. The other 2 infants were identified in a timely fashion and treated and had no sequelae. Of interest, had the "guidelines" been followed, 3 cases would have experienced delays in treatment (no statistical difference) but there would have been substantially more infants tested, treated, and hospitalized.4

What does this all mean and how is it relevant to this case? First, it is important to realize that the PROS clinicians were experienced, with a median age of 45. In other words, to allow a suitable place for clinician judgment may require truly experienced clinical judgment. When clinical judgment becomes experienced judgment is a difficult question, but this model is clearly not for interns in July, unless they have consulted with an attending physician.

Who decides?

The second point is to question who actually makes the decision. In this hypothetical case the Kendalls were told that the information was complex and the residents didn't want to confuse them. In fact, almost all parents have to deal with complex information and decisions in their personal and professional lives, and few are as critical as those pertaining to the health of their children. You have their undivided attention! And the information can be presented in a meaningful way to help the parents participate in active decision making. In some situations clinicians should be fairly directive: "Jason looks very ill to us; he is only 2 weeks old and is minimally responsive. We are concerned enough that we plan to do a number of tests, including a spinal tap for which we will need your permission, after which we will start antibiotics and plan to observe him in the hospital until we are certain of the best course." The PROS Febrile Infant Study provides valuable information on the risks of serious disease given various clinical findings. Most of the findings of the PROS study are consistent with the intent of the guidelines, placing the sickest-appearing, youngest, and most febrile infants at highest risk. One of the values of this large study is that it allows clinicians to estimate the absolute risk of various scenarios in addition to the relative risks associated with clinical features. Therefore, another scenario could sound like this: "Even though Suzy is only 5 weeks old, she is very interactive and appears only minimally ill. With a temperature of 38.3 C, we estimate that her risk of serious illness is less than half a percent. While we could go ahead and do some blood tests if you are concerned, we have an option of following her closely by seeing her again in the morning, or sooner if you like. I would like to examine her urine today. If that is okay, you could take her home. Do you have our phone number if you need to call?" This gives the parent the option of asking questions, as well as considering whether they are risk-averse and wish more laboratory testing given the probabilities presented.

While guidelines certainly have a role in clinical medicine, they should never be viewed as commandments. In some settings—such as busy emergency rooms serving patients with whom patient follow-up is challenging—better adherence to guidelines may be appropriate. Community practitioners caring for patients who can be followed closely can exercise individualized clinical judgment along with information generated from the PROS study and knowledge about the individual family to provide optimal care. The bottom line for this debate was captured by a clinician after poring over much of the data, including risks and odds ratios, from the PROS study (Maureen Shannon, personal communication): "If you want commandments or God, go to church; if you want odds, go to Vegas; if you want good clinical care, go to a good clinician."


  1. Roberts KB. Young, febrile infants: A 30 year odyssey ends where it starts. JAMA. 2004;291(10):1261-1262.
  2. DeAngelis C, Joffe A, Wilson M, et al. Iatrogenic risks and financial costs of hospitalizing febrile infants. Am J Dis Child. 1983;137(12):1146-1149.
  3. Pantell RH, Naber M, Lamar R, et al. Fever in the first six months of life: risks of underlying serious infection. Clin Pediatr. 1980;19(2):77-82.
  4. Pantell RH, Newman TB, Bernzweig J, et al. Management and outcomes of care of fever in early infancy. JAMA. 2004;291(10):1203-1212.


Virtual Mentor. 2004;6(12):531-533.



The people and events in this case are fictional. Resemblance to real events or to names of people, living or dead, is entirely coincidental. The viewpoints expressed on this site are those of the authors and do not necessarily reflect the views and policies of the AMA.