Neonatal Fever (30 d - 60 days) - Curbside
Neonatal Fever (30 d - 60 days)
Editors: Dan Imler, MD
Inclusion Criteria  (Any one criteria present)
  • Fever > 38.0 C (100.4 F) x1 at home, OSH or in ED
  • Hypothermia < 36.0 (96.8 F) x1 at home, OSH or in ED
Exclusion Criteria
  • Immunosuppresed, cancer
  • Central venous catheter
  • Ventriculoperitoneal shuts

Consider pediatric or neonatal consult

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Evidence
Total Notes: 14
Evidence

1 Fever in neonates

The febrile 30 - 60 day old infant has long been a confusing patient for physicians. Evidence strongly suggests that neonates in this age group who develop fever are at risk of serious bacterial infection. However, identifying which patients are a high risk and should receive empiric antibiotics by history and physical alone has been shown to inadequately detect all infants with SBI. Therefore a risk based laboratory approach has been preferred.



References:
  1. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life.
    Baskin MN
    Pediatr Ann. 1993;22(8):462.

2 Fever definition

Most studies support a temperature cutoff of 38.0 C (100.4 F) as a concerning fever for serious bacterial infections in neonates. Of note, caretaker report of measured fever is associated with SBI, however tactile fever is not.

Bundling has been noted to cause increased temperatures in neonates, although attributing an elevated temperature to bundling should be taken with caution. Repeat temps without use of antipyretics should be attempted in any neonate before using bundling as the cause for fever. In addition, any fever greater than 38.5 C or any rectal temp greater than 38.0 C should be followed by septic workup.



References:
  1. Difficulties in universal application of criteria identifying infants at low risk for serious bacterial infection.
    Anbar RD, Richardson-de Corral V, O'Malley PJ
    J Pediatr. 1986;109(3):483.

3 Toxic appearing neonate

Up to 45 percent of ill appearing neonates will have a serious bacterial infection. Time can make a difference in the outcomes of these patients and antibiotics should not be delayed to obtain cultures. These infants should be admitted to NICU or PICU and should have a full septic workup and begin broad spectrum antibiotics.



References:
  1. Reliability of observation variables in distinguishing infectious outcome of febrile young infants.
    Bonadio WA, Hennes H, Smith D, Ruffing R, Melzer-Lange M, Lye P, Isaacman D
    Pediatr Infect Dis J. 1993;12(2):111.
  2. Predictive model for serious bacterial infections among infants younger than 3 months of age.
    Bachur RG, Harper MB
    Pediatrics. 2001;108(2):311.

4 Laboratory Studies

For well-appearing infants with a rectal temperature ≥38.0 C, laboratory testing can help determine which patients are at low risk for SBI.

For most studies a WBC count of less than 15k has been used to identify low risk criteria (with bands no more than 1500/microL). Blood culture should be performed in all patients to both determine the possibility of SBI as well as to guide antibiotic therapy.

All children in this age group are still at significant risk for UTI. This urine should be collected by catheter or suprapubic aspiration as bag urines have been shown to have high contamination rates. Of note, up to 20 percent of neonates with pyelonephritis will not have evident pyuria on UA so culture must always be obtained.

Inflammatory mediators such as WBC, ANC, CRP and Procalcitonin have been used to help identify low risk patients. Recently the use of Procalcitonin has gathered more attention as it has better sensitivity and specificity than WBC, ANC or CRP. At the current time we still recommend the use of Procalcitonin as an adjunct marker to the CBC, however, it may be considered in isolation as more data becomes available.

Molecular assays will need further validation before they can be recommended for routine clinical use as well.



References:
  1. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.
    Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Dagan R, Powell KR
    Pediatrics. 1994;94(3):390.
  2. Management and outcomes of care of fever in early infancy.
    Pantell RH, Newman TB, Bernzweig J, Bergman DA, Takayama JI, Segal M, Finch SA, Wasserman RC
    JAMA. 2004;291(10):1203.
  3. Clinical and demographic factors associated with urinary tract infection in young febrile infants.
    Zorc JJ, Levine DA, Platt SL, Dayan PS, Macias CG, Krief W, Schor J, Bank D, Shaw KN, Kuppermann N.
    Pediatrics. 2005;116(3):644.
  4. Clinical policy for children younger than three years presenting to the emergency department with fever.
    American College of Emergency Physicians Clinical Policies Committee, American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever
    Ann Emerg Med. 2003;42(4):530.
  5. Is urine culture necessary to rule out urinary tract infection in young febrile children?
    Hoberman A, Wald ER, Reynolds EA, Penchansky L, Charron M
    Pediatr Infect Dis J. 1996;15(4):304.
  6. Role of Serum Procalcitonin in Identifying Young Febrile Infants With Invasive Bacterial Infections: One Step Closer to the Holy Grail?
    Kuppermann N, Mahajan P
    JAMA Pediatr. 2016 Jan;170(1):17-8.
  7. Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants.
    Milcent K, et. al.
    JAMA Pediatr. 2016 Jan;170(1):62-9.

5 Respiratory Symptoms

Although the primary concern in neonates with fever is for an SBI, most of these patients have a viral syndrome as their causative etiology. If the patient has viral symptoms nasopharyngeal PCR evaluation for respiratory viral pathogens may help in the management of the patient while admitted, especially relating to cohorting of patients in the hospital. We recommend that all neonatal febrile patients undergo PCR testing if they have viral symptoms.

Neonates without respiratory symptoms are highly unlikely to have an underlying cause of their fever identified by chest x-ray. However if a neonate displays respiratory rate >50 breaths/min, rales, rhonchi, retractions, wheezing, coryza, grunting, stridor, nasal flaring, or cough an AP chest x-ray is likely to result in an abnormal finding.

Of note, even with an abnormal finding on CXR, a viral etiology is still most likely.



References:
  1. Clinical policy for children younger than three years presenting to the emergency department with fever.
    American College of Emergency Physicians Clinical Policies Committee, American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever
    Ann Emerg Med. 2003;42(4):530.
  2. The futility of the chest radiograph in the febrile infant without respiratory symptoms.
    Bramson RT, Meyer TL, Silbiger ML, Blickman JG, Halpern E
    Pediatrics. 1993;92(4):524.
  3. Diagnostic approach to pneumonia in children.
    Correa AG
    Semin Respir Infect. 1996;11(3):131.
  4. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections.
    Levine DA, Platt SL, Dayan PS, Macias CG, Zorc JJ, Krief W, Schor J, Bank D, Fefferman N, Shaw KN, Kuppermann N, Kuppermann N,
    Pediatrics 2004 Jun;113(6):1728-34.
  5. Low risk of bacteremia in febrile children with recognizable viral syndromes.
    Greenes DS, Harper MB,
    Pediatr. Infect. Dis. J. 1999 Mar;18(3):258-61.

6 Diarrhea

Neonates with diarrhea may have a stool pathogen as the primary source of their fever (they are at low risk of this without diarrhea). Stool culture is recommended to all febrile neonatal patients. Additional stool studies should be performed if the patient has associated risk factors.



References:
  1. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.
    Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Dagan R, Powell KR
    Pediatrics. 1994;94(3):390.

7 Cellulitis

Cellulitis or other focal bacterial infection raises concern for methicillin-resistant staphylococcus aureus infection in the febrile neonate. Given the high mortality and morbidity associated with these infections in this age group, all patients should be started on IV vancomycin.



References:

8 Viral Syndrome

Although the primary concern in neonates with fever is for an SBI, most of these patients have a viral syndrome as their causative etiology. If the patient has viral symptoms nasopharyngeal PCR evaluation for respiratory viral pathogens may help in the management of the patient while admitted, especially relating to cohorting of patients in the hospital. We recommend that all neonatal febrile patients undergo PCR testing if they have viral symptoms.



References:
  1. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections.
    Levine DA, Platt SL, Dayan PS, Macias CG, Zorc JJ, Krief W, Schor J, Bank D, Fefferman N, Shaw KN, Kuppermann N
    Pediatrics. 2004;113(6):1728.
  2. Low risk of bacteremia in febrile children with recognizable viral syndromes.
    Greenes DS, Harper MB
    Pediatr Infect Dis J. 1999;18(3):258.

9 Low risk criteria

Many studies have looked at identifying neonatal patient populations that are low risk for meningitis through history laboratory studies. This is important as 10 to 35 percent of LPs are traumatic/unsuccessful and prolonged antibiotics and hospitalization may occur in patients who do not need this treatment. Although there is no current consensus on the topic, we suggest:

  • Well appearing with no past medical history
  • Serum WBC > 5k and < 15k mm3
  • Absolute bands < 1.5k mm3
  • < 10 WBC/hpf, negative leukocyte esterase, negative nitrites and negative Gram Stain on UA
  • CSF WBC <10/mm3 for patients 30 to 60 days
  • Chest x-ray lacking an infiltrate if obtained

Hyperpyrexia (as defined by temperature greater than 41 C or 106F) has been shown as a significant risk factor for SBI. Because of this, all infants with a fever document to reach this range should have a full rule out sepsis evaluation including LP, empiric antibiotics and admission.



References:
  1. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone.
    Baskin MN, O'Rourke EJ, Fleisher GR
    J Pediatr. 1992;120(1):22.
  2. Outpatient management without antibiotics of fever in selected infants.
    Baker MD, Bell LM, Avner JR
    N Engl J Med. 1993;329(20):1437.
  3. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.
    Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Dagan R, Powell KR
    Pediatrics. 1994;94(3):390.
  4. Outpatient management of selected infants younger than two months of age evaluated for possible sepsis.
    McCarthy CA, Powell KR, Jaskiewicz JA, Carbrey CL, Hylton JW, Monroe DJ, Meyer H
    Pediatr Infect Dis J. 1990;9(6):385.
  5. Clinical policy for children younger than three years presenting to the emergency department with fever.
    American College of Emergency Physicians Clinical Policies Committee, American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever
    Ann Emerg Med. 2003;42(4):530.
  6. Prospective evaluation of the risk of serious bacterial infection in children who present to the emergency department with hyperpyrexia (temperature of 106 degrees F or higher).
    Trautner BW, Caviness AC, Gerlacher GR, Demmler G, Macias CG.
    Pediatrics. 2006 Jul;118(1):34-40.
  7. Is a lumbar puncture necessary when evaluating febrile infants (30 to 90 days of age) with an abnormal urinalysis?
    Paquette K, Cheng MP, McGillivray D, Lam C, Quach C.
    Pediatr Emerg Care. 2011 Nov;27(11):1057-61.

10 Treatment of UTI

The Pediatric Emergency Medicine Collaborative Research Committee completed a large, multicenter study which showed that sterile CSF pelocytosis occurs in 18 percent of febrile infants 29 to 60 days of age with UTIs (CSF WBC ≥10/mm3). However, these patients had a very low risk of adverse events with their treatment for UTI. A 2011 study looked at 392 febrile patients (57 with meningitis) 30-90 days old and only found one with a positive UA and meningitis. This patient would not meet low risk criteria for exclusion of LP. Additional studies showed that well appearing patients older than 30 days appear to be very low risk for meningitis when treated outpatient with oral antibiotics. Therefore neonates 30 - 60 days old who are well appearing who have a UTI on UA may not necessarily need an LP to rule out meningitis (if low risk).

There is no definitive evidence regarding the need to admit a patient in this age group if they have a presumed UTI, are low risk and meet discharge criteria and can be followed up within 24 hours. This decision to admit at this point should be based on the provider's opinion of the safety of outpatient therapy in relation to the specific patient characteristics.



References:
  1. Urinary tract infections in 1- to 3-month-old infants: ambulatory treatment with intravenous antibiotics.
    Doré-Bergeron MJ, Gauthier M, Chevalier I, McManus B, Tapiero B, Lebrun S.
    Pediatrics. 2009 Jul;124(1):16-22.
  2. Sterile cerebrospinal fluid pleocytosis in young febrile infants with urinary tract infections.
    Schnadower D1, Kuppermann N, Macias CG, Freedman SB, Baskin MN, Ishimine P, Scribner C, Okada P, Beach H, Bulloch B, Agrawal D, Saunders M, Sutherland DM, Blackstone MM, Sarnaik A, McManemy J, Brent A, Bennett J, Plymale JM, Solari P, Mann DJ, Dayan PS;
    Arch Pediatr Adolesc Med. 2011 Jul;165(7):635-41.
  3. The age-related risk of co-existing meningitis in children with urinary tract infection.
    Tebruegge M, Pantazidou A, Clifford V, Gonis G, Ritz N, Connell T, Curtis N.
    PLoS One. 2011;6(11):e26576.
  4. Is a lumbar puncture necessary when evaluating febrile infants (30 to 90 days of age) with an abnormal urinalysis?
    Paquette K, Cheng MP, McGillivray D, Lam C, Quach C.
    Pediatr Emerg Care. 2011 Nov;27(11):1057-61.

11 CSF Enterovirus

All neonates less than 30 days with CSF WBC > 10/mm3 should be considered high risk of meningitis. Although a majority of neonatal meningitis is viral and self-limited, immediate aggressive treatment should be undertaken.

We recommend that all patients get CSF PCR testing for enterovirus. Infants on which an enterovirus PCR was obtained had a decreased length of stay by 26 percent.



References:
  1. Viral meningitis and encephalitis: traditional and emerging viral agents.
    Romero JR, Newland JG
    Semin Pediatr Infect Dis. 2003;14(2):72.
  2. Cerebrospinal fluid enterovirus testing in infants 56 days or younger.
    Dewan M, Zorc JJ, Hodinka RL, Shah SS.
    Arch Pediatr Adolesc Med. 2010 Sep;164(9):824-30.

12 LP unsuccessful

10 to 35 percent of LPs are traumatic. If an LP is attempted and unsuccessful a pertinent course of action would be to admit the patient and start empiric antibiotics. A repeat LP should be attempted after hydration if possible. If urine and blood cultures are negative, the patient was clinically well throughout their course and CSF is never obtained, it may be acceptable to either discharge the patient after 48 hours or finish a meningitic course of antibiotics.



References:
  1. Distinguishing traumatic lumbar puncture from true subarachnoid hemorrhage.
    Shah KH, Edlow JA
    J Emerg Med. 2002;23(1):67-74.
  2. Risk factors for traumatic or unsuccessful lumbar punctures in children.
    Nigrovic LE, Kuppermann N, Neuman MI
    Ann Emerg Med. 2007;49(6):762-771.

13 Patient on antibiotics

Antibiotics may mask underlying infections as laboratory results may be negative. These patients should still undergo a full rule out sepsis evaluation. Consideration can go into observing the patient for 24-48 hours off to monitor for worsening symptoms and positive cultures.



References:
  1. Bacterial meningitis. Effect of antibiotic treatment on cerebrospinal fluid.
    Blazer S, Berant M, Alon U
    Am J Clin Pathol. 1983;80(3):386.
  2. Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis.
    Kaplan SL, Smith EO, Wills C, Feigin RD
    Pediatr Infect Dis. 1986;5(6):626.

14 Concomitant viral infections

In patients older than 30 days the risk of SBI appears to be lower if they are diagnosed with a viral infection (influenza or RSV bronchiolitis). One studies showed no patients with meningitis if they were diagnosed with clinical bronchiolitis. However, the risk for UTI and bacteremia still remain significant. Because of this, obtaining serum and urine lab tests is appropriate in these patients.



References:
  1. Influenza virus infection and the risk of serious bacterial infections in young febrile infants.
    Krief WI, Levine DA, Platt SL, Macias CG, Dayan PS, Zorc JJ, Feffermann N, Kuppermann N,
    Pediatrics. 2009;124(1):30.
  2. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections.
    Levine DA, Platt SL, Dayan PS, Macias CG, Zorc JJ, Krief W, Schor J, Bank D, Fefferman N, Shaw KN, Kuppermann N
    Pediatrics. 2004;113(6):1728.
  3. Occult serious bacterial infection in infants younger than 60 to 90 days with bronchiolitis: a systematic review.
    Ralston S, Hill V, Waters A
    Arch Pediatr Adolesc Med. 2011 Oct;165(10):951-6.