FEVER WITHOUT A SOURCE DEFINITION: As the title implies, fever without a source is a fever without an identifiable cause on history

or physical exam. Fever is defined as >100.4 or 38.0. Because the implications of fever without a source are different for different age groups the epidemiology, presentation, differential, work up and treatment will depend on the age of the child at presentation. EPIDEMIOLOGY: 5-10% of all children presenting with fever have no source. Birth - 2 months EPIDEMIOLOGY/DIFFERENTIAL Many infants with a fever will have a viral infection. However, the risk of serious bacterial infection (SBI) is greatest in this age group. Bacterial illness includes sepsis, meningitis, urinary tract infections (UTI), enteritis, osteomyelitis, and suppurative arthritis. Other possible infections include otitis media, pneumonia, omphalitis, mastitis and skin or soft tissue infections. The most common infections are UTIs followed by bacteremia and then meningitis. In infants less that 1 month old the rate of SBI is 9-14% and in infants between 1 and 2 months old the rate is 5-9%. Group B streptococcus, Escherichia coli, Listeria monocytogenes, and herpes simplex virus are the most common bacterial illnesses in the <1 month age group. Salmonella, Neisseria meningitides, Streptococcus pneumoniae, Haemophilus influenzae type b, Staphylococcus, Enterococcus, and Enterobacter are all possible. Even when a viral illness is present, there is still the possibility of a co-existing SBI. In one study of infants 29-60 days old, 6% had an SBI even though they were RSV positive versus 12% in those that were RSV negative. The most common co-infection was UTI in this group. PRESENTATION: Infants with fever may present with signs of a viral illness such as cough and rhinorrhea or diarrhea and vomiting. However, given the higher likelihood of SBI a careful history and physical is warranted in addition to a more involved work up of the patient. In young infants, it can be particularly difficult to assess the degree of illness. The Yale observation score has been used to determine a clinicians ability to detect serious illness on exam and history. The score is based on quality of cry, reaction to parents, state variation, color, hydration and response to social overtures. However, the sensitivity of the score has been shown to be poor as the exam is often unreliable even when performed by experienced physicians. WORK UP: All patients less than 2 months old should under go a CBC, blood culture, urinalysis with culture and lumbar puncture. If symptoms suggest a possible pneumonia or gastroenteritis, a chest x-ray and/or stool studies should also be performed. One must also keep in mind the risk for HSV in infants < 6 weeks, especially in an infant who is born to a mother with a primary HSV infection. However, because the primary HSV infection in the mother can be asymptomatic or nonspecific, one should also consider sending an HSV PCR and other viral cultures (conjunctiva, skin lesion, NP, rectal) in an infant who is ill appearing, premature, presents with seizures or a vesicular rash, has a CSF pleocytosis or elevated hepatic enzymes. TREATMENT: Treatment should be based on age and clinical and laboratory findings. 1. 0-28 days: As the risk of SBI is relatively high, the immune system is immature, the exam can be unreliable and the pathogens virulent, all infants less than 28 days old should be admitted and started on antibiotics. This is true even when a viral etiology is found. Ampicillin AND cefotaxime or gentamicin are the drugs of choice. Acyclovir should be used if herpes is suspected. 2. 29-60 days: A variety of institutions have attempted to assess the risk of SBI in infants to help guide treatment. Criteria exist from Philadelphia, Boston, Rochester and Baraff et al published in 1993 by the AAP. Not one is used universally and they differ based on the age included, the degree of temperature, the white blood cell count and whether or not an LP, CXR or stool culture is required. In general, infants considered high risk (see figure 1) by clinical exam or laboratory results should be admitted and started on

antibiotics after an LP is performed. Low risk infants can be treated as outpatients or inpatients taking into consideration the needs of the family, primary care judgment, outpatient follow-up, and communication with primary care provider (PCP). If antibiotics are given, a third generation cephalosporin should be used. Ampicillin or vancomycin may be considered if the patient looks ill or UTI, enterococcus, listeria or gram positive cocci are considered. High Risk (not consistent with one known criteria) Laboratory WBC >15000, WBC<5000 Urine micro >5WBCs/hpf, leukocyte esterase or nitrite positive CSF WBC> 22, protein >150mg, glucose <50-70% serum

Clinical exam Toxic poor perfusion cap refill >2 seconds cyanosis lethargy inconsolable poor or no eye contact mottling hyper or hypoventilation

2 months - 3 years EPIDEMIOLOGY/DIFFERENTIAL: Fever with no identifiable source in this age group should be further investigated if >39.0 C or 102.2 F. The most common cause is viral but bacterial infections are possible including UTIs, bacteremia, pneumonia, osteomyelitis, focal skin infections and meningitis. Prior the HIB and PCV7 vaccines, occult bacteremia caused by strep pneumoniae and H. Influenzae type B were of concern. The prevalence of occult bacteremia was estimated to be between 3-11% prior to the HIB vaccine. With both the PCV7 and HIB vaccine, the prevalence has decreased to less than 1%. The risk of meningitis or death in those with bacteremia is approximately 1.8%. PRESENTATION: Older infants and toddlers can present with fever and no localizing signs. A careful history and physical is always necessary. Those with fevers >40 C have a higher likelihood of occult bacteremia, however many children with temperatures <40 C also can have bacteremia. In addition, the response to acetaminophen or ibuprofen does not differentiate between those with and without bacteremia. Work up and management should be guided by the childs clinical appearance. The Cincinnati Guidelines define children in this age group as well appearing (playful, feeding well, easily consolable, no dehydration or respiratory distress), ill appearing (irritable with crying, mild to moderate dehydration, normal perfusion) and toxic appearing (lethargy, hypothermia, cyanosis, poor perfusion, suspected meningitis). WORKUP: In those who are well appearing, not at risk for UTI (males circumcised > 6 months, males uncircumcised >1 year, females >2 years and no history of UTI) and have been immunized can be managed at home without a laboratory evaluation. This should only be done if there is reliable follow-up, anticipatory guidance is given and the PCP and caregivers are in agreement or when there is a recognizable viral condition (general URI and acute gastroenteritis not included). In those at risk for UTI a urinalysis and urine culture should be performed (males circumcised < 6 months, males uncircumcised <1 year, females <2 years or history of UTI). In patients who are ill appearing, had contact with meningitis, fever >40 C or incomplete PCV7 series for age, a CBC and blood culture should be performed. TREATMENT: When a laboratory work up is carried out, if the CBC is abnormal (defined as ANC>10.000 or WBC >15000) IM ceftriaxone should be considered. Antibiotics are not recommended for those without a source of bacterial infection in the absence of a laboratory work up. Patients should be admitted if they are unable to tolerate oral intake, follow up is unavailable, respiratory distress, hypoxemia or clinical concern is present.