Fever Without a Source in the 1- to 3-Month-Old Infant Case File
Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS
Case 28
A 10-week-old infant is brought to the emergency department (ED) by his mother for 1 day of fever. The mother tells you that her son was delivered vaginally at full term and was the product of an uncomplicated pregnancy. He has had regular well-baby checks and has been gaining weight appropriately. He has met his normal developmental milestones and vaccinations are up-to-date. He has had no prior illnesses. This morning his mother noticed he felt warm to the touch and discovered an axillary temperature of 101°F. No other signs or symptoms of infection including runny nose, cough, difficulty breathing, rash, nuchal rigidity, seizure activity, abdominal distension, vomiting, or diarrhea. She states her son has been breast-feeding less than normal, but overall has had a normal number of wet diapers. She is very concerned because this is her first child and he has never had a fever before.
On examination, the child is found to have a heart rate of 180 beats per minute, a blood pressure of 90/50 mm Hg, a respiratory rate of 40 breaths per minute, an oxygen saturation of 99% on room air, and a rectal temperature of 102.7°F. He is overall well appearing and has an unremarkable physical examination. Although he cries when you perform the examination, his mother is able to console him easily.
⯈ What is the most likely diagnosis?
⯈ What is the next step in management?
⯈ What is the best therapy?
ANSWER TO CASE: 28
Fever Without a Source in the 1- to 3-Month-Old Infant
Summary: A previously healthy 10-week-old infant is brought in by his mother for fever The cause of the fever is not clearly identified by the history or physical examination. His vital signs in the emergency department are significant for fever and tachycardia. His examination is unremarkable.
- Most likely diagnosis: Fever without a source (FWS).
- Next step: Order CBC, blood cultures, urinalysis, urine culture. You may also order stool studies, a chest x-ray, and perform a lumbar puncture depending on the clinical presentation.
- Best therapy: It is up to physician discretion to decide which well-appearing infants with fever without a source should receive antibiotics. If antibiotics are given, the best drug is ceftriaxone, either IV or IM.
ANALYSIS
Objectives
- Understand the appropriate workup for fever without a source in the well-appearing 1- to 3-month-old infant.
- Appreciate the controversy regarding the management of fever without a source in this age group.
- Learn the treatment options for fever without a source in a 1- to 3-month-old infant.
Considerations
This 10-week-old infant presented with fever without any other signs or symptoms of infection including runny nose, cough, difficulty breathing, rash, nuchal rigidity, seizure activity, abdominal distension, vomiting, or diarrhea. Importantly, the emergency physician must be aware that the 1- to 3-month-old infant will not manifest the same signs of infection as an older child. For this reason, the workup of fever in this age group must remain broad and one must have a low threshold for both further testing and treatment with antibiotics.
Approach To:
Fever Without a Source in the 1- to 3-Month-Old Infant
DEFINITIONS
FEVER WITHOUT A SOURCE: Fever without a source is an acute febrile illness in which the etiology of the fever is not apparent after a careful history and physical examination. A rectal temperature greater than 38°C (100.4°F) is defined as a fever.
SERIOUS BACTERIAL ILLNESS (SBI): Illnesses including bacteremia, pneumonia, urinary tract infection, skin and soft tissue infections, bone and joint infections, enteritis, or meningitis due to a bacterial pathogen.
CLINICAL APPROACH
Diagnosis of Potential Fever in the 1- to 3-Month-Old Infant
While many parents will bring in their infants for a chief complaint of fever, not all parents will have actually taken their child’s temperature with a thermometer. If an infant has had a rectal temperature more than 38°C at home but is afebrile and well appearing in the emergency department, this infant still requires full workup for fever. If the parent only reports a tactile fever and the infant is afebrile and well appearing in the emergency department, no laboratory testing for fever workup is required. Temperature must be measured with a rectal thermometer in order to rule out a fever. Axillary and tympanic membrane thermometers are not adequate to evaluate for fever in an infant. If an infant is brought in bundled and has a mildly elevated temperature, it is worthwhile to recheck a rectal temperature 15 minutes after unbundling the infant. However, a temperature more than 38.5°C should never be attributed to bundling.
Evaluation of Fever Without a Source in the 1- to 3-Month-Old Infant
The evaluation of fever in this age group has changed dramatically in the last 30 years in the wake of vaccines targeting haemophilus influenzae type b and Streptococcus pneumoniae. These vaccines have dramatically decreased the burden of SBI in this age group. Prior to the development of these vaccines, the majority of febrile infants in this age group were hospitalized and often started on empiric antibiotic therapy. Morbidity and mortality for SBI was high and early clinical identification was very difficult.
Given the controversy and difficulties identifying infants with SBI several decision rules have been developed. These are the Rochester, Boston, and Philadelphia criteria, each using a combination of factors including history, physical examination, and laboratory parameters to identify low-risk infants. Although all these criteria use slightly different testing strategies, all of the criteria support the use of CBC, blood cultures, urinalysis, and urine culture to identify infants at low risk for SBI. Test results suggestive of high risk for SBI include WBC greater than or equal to 15,000/mm3 or less than or equal to 5000/mm3, a band-to-neutrophil ratio of greater than or equal to 0.2, a urine dipstick test positive for nitrite or leukocyte esterase, or a finding of greater than or equal to 5 WBCs/hpf or organisms seen on
Gram stain.
Routinely obtaining chest x-rays and lumbar punctures in this age group are somewhat more controversial. Although there is disagreement between the decision rules, one meta-analysis of a combined group of 361 febrile infants found that infants which have tachypnea >50 breaths per minute, rales, ronchi, retractions, wheezing, coryza, grunting, stridor, nasal flaring, or cough should have a chest x-ray.
Similar to chest x-ray, routine lumbar puncture is another area of controversy among the decision rules. Several observational studies suggest that infants can be identified as low risk for SBI without performing a lumbar puncture. However, other physicians feel that the significant morbidity and mortality associated with bacterial meningitis outweighs the low incidence of the disease, and thus argue in support of routine lumbar puncture in the workup of fever without a source. Cerebrospinal fluid (CSF) with greater than or equal to 8 WBC/mm3 or organisms on Gram stain is considered high risk for SBI. Additionally, sending stool for WBCs and culture is recommended for infants in this age group with diarrhea. Greater than 5 WBC/hpf in the stool specimen is considered high risk for SBI.
While this case has focused on the well-appearing 1- to 3-month-old infant with fever without a source, it is worthwhile to note that ill-appearing infants in this age group have a much higher risk of SBI, and all of these infants should be treated with empiric antibiotics and admitted to the hospital. Up to 45% of these infants will test positive for SBI.
Pathogens
Routine vaccinations with Haemophilus influenzae type b vaccine (Hib) and heptavalent pneumococcal conjugate vaccine (PCV7) have dramatically decreased the rates of SBI infants. After the introduction of the Hib vaccine, the majority (90%) of infections were due to pneumococcus. The PCV7 vaccine further changed the landscape of SBI, decreasing the incidence of invasive pneumococcal disease 65% to 80% in children younger than 3 years of age. Although much less common, other pathogens are emerging as prominent causes of SBI in this age group, including E Coli, Staphylococcus aureus, Neisseria meningitides, Salmonella species, and Streptococcus pyogenes. Furthermore, non-vaccine serotypes of S Pneumoniae are noted to be increasingly prevalent in this age group.
Treatment
Antibiotics must be considered for all 1- to 3-month-old infants with fever without a source. The empiric antibiotic of choice is c eftriaxone, which may be given IV or IM. The regular dose is 50 mg/kg; however, if meningitis is suspected, the dose should be increased to 100 mg/kg. If lumbar puncture is not performed, antibiotics should be withheld because giving empiric antibiotics in this situation could mask the presentation of bacterial meningitis on follow-up examination. For ill-appearing infants in this age group, consideration should be given to augmenting empiric ceftriaxone by adding vancomycin to cover for methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumonia resistant to ceftriaxone. Ampicillin should also be considered for the ill-appearing infant to cover for possible Listeria monocytogenes.
COMPREHENSION QUESTIONS
28.1. An 8-week-old previously healthy infant, product of a full-term pregnancy, is brought by his older sister to the emergency department for a fever up to 101.2°F. The sister, who is 17 years old, states that she is the primary caretaker for her brother because the only adult at home is her mother who is struggling with cocaine and alcohol abuse. The sister states that although her brother has not been eating well, he is taking in a normal amount of formula and has not had cough, runny nose, altered behavior, vomiting, or diarrhea. Overall, the patient is well appearing. You perform an appropriate workup for this infant with FWS and find a WBC count of 10,000/mm3, and a UA with 2 WBCs/hpf. You also elect to do an LP and the CSF shows 1 WBC/mm3 and no organisms on Gram stain. What is the most appropriate disposition for this patient?
A. Discharge the patient home after giving a dose of IV Ceftriaxone.
B. Discharge the patient home but do not give any antibiotics.
C. Give a dose of IV ceftriaxone and admit the patient to the hospital.
D. Order a chest x-ray, stool WBCs and culture, and then admit the patient to the hospital.
28.2. An 11-week-old male infant is brought in by his mother for 4 days of fever (Tmax 100.8°F) associated with cough and runny nose. The child was the product of a full-term healthy pregnancy and his vaccines are up-to-date. He is overall well appearing and has normal vital signs. A chest x-ray demonstrates no evidence of pneumonia. A rapid respiratory syncytial virus (RSV) test comes back positive. Which of the following statements most accurately describes the risk of SBI in the RSV positive infant?
A. SBI is just as common in RSV-positive infants as in RSV-negative infants.
B. SBI is less common in RSV-positive infants as in RSV-negative infants.
C. SBI is equally as common in RSV-positive infants as in RSV-negative infants.
D. There is no risk of SBI in the febrile infant with a positive RSV test.
28.3. A 9-week-old well-appearing female infant is brought in to the emergency department with a chief complaint of a fever up to 102°F at home. The infant has not had any vomiting or cough and the examination is unremarkable including a thorough skin examination. In the ED, the infant is afebrile but had been given ibuprofen by mom 2 hours prior to arrival. A catheter urinalysis comes back positive for 20 WBCs/hpf. What is the best management for this patient?
A. Send urine cultures, give her IV antibiotics, and admit her to the pediatric service.
B. Send urine cultures, give her PO antibiotics, and discharge her home.
C. Give her an IM shot of ceftriaxone and send her home with PO antibiotics.
D. Send urine cultures, give IV or IM antibiotics, and evaluate the social situation.
28.4. A 6-week-old male infant is brought in by his parents for evaluation of fever of 39°C. The infant is ill appearing and lethargic and does not want to breastfeed. His parents also reported that his cry sounds different. The patient is given antipyretics, a bolus of 20 cc/kg IV fluids and labs are sent. A thorough examination including skin does not reveal any source of infection, and urinalysis, chest x-ray, and CSF are all normal and cultures are sent. What is the best management of this patient?
A. Give him an IM shot of ceftriaxone and discharge home with close follow-up.
B. Give him IV ceftriaxone and admit to the pediatric service.
C. Give him IV ceftriaxone, vancomycin, and ampicillin and admit to the pediatric service.
D. Do not give any antibiotics at this time and admit to the pediatric service for observation.
ANSWERS
28.1 C. This case demonstrates the importance of good follow-up and an adequate social situation when considering discharging the well-appearing infant with FWS. In order to discharge a well-appearing infant with FWS, one must ensure follow-up within 24 hours. There must also be adequate social support to ensure the patient can be brought back to the hospital if his condition worsens. In general, this means that the patient’s family should have access to a telephone and transportation. In this case, the social situation is less than ideal as a minor is primarily caring for the patient and the only adult in the family is incapacitated by polysubstance abuse to the point that she has not even come to the hospital with her ill infant. There is no indication for a chest x-ray or stool studies in this patient as he has no respiratory symptoms and no diarrhea.
28.2 B. A positive RSV test in a 1- to 3-month-old infant with a fever decreases the risk of SBI, but does not completely eliminate this risk. Most studies demonstrate that the risk of SBI in the RSV-positive population is decreased by approximately 50%. The most common SBI in the RSV-positive patient is a urinary tract infection. There are no studies at this time which have been powered enough to detect difference in rates of bacteremia and meningitis in RSV-positive and RSV-negative patients as both bacteremia and meningitis in this age group is relatively uncommon. Thus, RSV-positive infants in this age group with fever should at least receive a urinalysis and urine culture. It remains unclear whether or not clinicians can safely forgo blood and spinal fluid testing in these same infants.
28.3 D. Urinary tract infection is the most common cause of SBI in infants with fever without a source and the prevalence has not changed with the PCV7 vaccine. A positive urine is defined as greater than10 WBCs per high power field. A negative urine dipstick or urinalysis does not exclude UTI as pyuria is absent on initial urinalysis in up to 20% febrile infants with pyelonephritis. Thus, a urine culture must be obtained on all patients. Additionally, catheter samples should always be obtained as bag specimens are often contaminated. Infants younger than 8 weeks of age should be admitted to the hospital. Wellappearing infants greater than 8 weeks may be discharged home if the parents are reliable and follow-up within 24 hours is possible. Infants younger than 3 months of age should be given parenteral antibiotics (ceftriaxone 50 mg/kg) with admission or discharge and may need additional parenteral doses even if discharged home.
28.4 C. Infants who have an abnormal cry and temperature greater than 38.5°C or are ill appearing have an increased risk of SBI. Up to 45% of ill-appearing young infants may have SBI and, thus, require extensive workup including blood, urine, CSF, and CXR. Ill-appearing infants in this age group should receive parenteral antibiotic therapy to cover the likely pathogens in this age group regardless of initial laboratory results (S pneumoniae, S aureus, N meningitides, H influenza type b) and should be admitted to the hospital. Of note, vancomycin should be administered to infants with soft tissue infection or CSF pleocytosis. In infants 29 to 60 days of age, ampicillin should also be given to cover Listeria monocytogenes.
References
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