ED Management of Fever and Neutropenia
in Infants and Children
All known oncology patients with fever1
Yes
Toxic appearing or critically
ill2?
Evaluate & treat
for septic shock,3
admit to PICU
No
Give Ceftriaxone 50 mg/kg via CVL4
Obtain on all patients:
CBC/manual diff, chem 7,
Bld Cx all CVL lumens5
Obtain only as indicated: CXR,6 rapid strep & throat cx,7
UA/Ur Cx,8 viral cx,9 stool cx,10
AAS,11 wound cx,12 surgery consult,13
LFTs/amylase/lipase
Neutropenia?14
No
Consult Peds Heme/Onc15
Determine disposition
Yes
Consult Peds Heme/Onc15
Initiate antibiotic therapy16
Observe neutropenic precautions17
Admit
1
Guideline for ED Management of Fever & Neutropenia in Children
Notes:
1 Fever=temp. > 38.0  C. X 2 or > 38.5  C. X 1 within past 24 hrs
2 Toxicity=altered mental status; poor eye contact; inappropriate response to
stimuli; abnormal vital signs; poor skin perfusion; cyanosis; grunting
3 For septic shock:
a. obtain CBC/manual diff, blood cx all CVL lumens or peripheral if no CVL
present, Type & Hold, PT/PTT, fibrinogen, fibrin degradation products
b. support BP with isotonic crystalloid (20 mL/kg boluses of NS or LR), vasopressors (dopamine 10-25 mcg/kg/min, epinephrine 0.1-1.0 mcg/kg/min,
norepinephrine 0.05-0.5 mcg/kg/min) as indicated
c. administer antibiotics: Vancomycin 40 mg/kg/day IV div Q8H + Cefepime
50 mg/kg/dose IV Q8H (max dose 2 gm)
4 If PCN or cephalosporin allergy, discuss with Heme-Onc.
5 Regarding peripheral blood cx: avoid if CVL is present; obtain only if no CVL.
6 Obtain CXR for: persistent cough; SaO2 < 97% (RA); abnormal lung exam;
tachypnea; increased work of breathing (flaring/grunting/retractions)
7 Obtain rapid strep & throat cx for: throat pain; tonsillar or pharyngeal
erythema/exudate. Send throat cx only if rapid strep negative.
8 Obtain clean voided specimen if possible (avoid catheterization) for symptoms or
signs of UTI.
9 Obtain viral cx of discrete oral/pharyngeal lesions. Treat with IV acyclovir if
history of HSV. Consider IV acyclovir if no history of HSV.
10 Obtain fecal leukocytes & stool cx for diarrhea
11 Obtain AAS (acute abdominal series), LFTs, amylase/lipase for: abdominal
pain; abnormal abdominal exam (tenderness, distension, abnormal bowel
sounds, masses or organomegaly). Evaluate for free air or signs/sx consistent
with typhilitis.
12 Obtain wound cx of any exudate at CVL site
13 Obtain surgical consult for: free air; or signs/sx consistent with typhilitis
14 Neutropenia = ANC < 500/mm3 or < 1,000/mm3 with predicted decline to
< 500/mm3
15 Peds Heme-Onc pager: 669-2131
16 Two options for inpatient antibiotics (unless cephalosporin or PCN allergy, then
discuss with Heme/Onc):
a. Cefepime (50 mg/kg/dose, max dose 6 gm/day) + Vancomycin (40 mg/kg/day
div Q6-8H, max dose 1 gm) if any of the following:
(1) clinically obvious and serious CVL-related infection
(2) substantial mucosal damage
(3) known colonization with β-lactam resistant S. pneumoniae or S.
aureus
(4) growth of a gram-positive organism from the blood (pending
identification and susceptibility testing)
2
Guideline for ED Management of Fever & Neutropenia in Children
(5) hypotension or other evidence of cardiovascular dysfunction
(6) recent treatment with systemic antibiotics
b. Otherwise cefepime (monotherapy)
17 Neutropenic precautions:
a. No IM injections UNLESS requested or approved by Heme/Onc. Apply
pressure following all IM injections in thrombocytopenic patients.
b. No rectal temps. or exams
c. No suppositories
d. No I&D procedures without Heme/Onc approval
e. No NG tubes, urinary catheters, suprapubic bladder aspirates or LPs
without Heme/Onc approval
f. No venipuncture or IV placement without betadine prep
References:
Hughes WT, Armstrong D, Bodey GP et al: 1997 Guidelines for the use of
antimicrobial agents in neutropenic patients with unexplained fever. Clin Infect Dis
1997;25:551-573
[Practice guidelines for treatment of febrile neutropenic patient.]
Mustafa MM, Carlson L, Tkaczewski I, et al. Comparative study of cefepime versus
ceftazidime in the empiric treatment of pediatric cancer patients with fever and
neutropenia. Pediatr Infect Dis J 2001;20:362-9
[Cefepime appears to be safe and effective compared with ceftazidime for initial empiric
therapy of febrile episodes in neutropenic pediatric cancer patients.
Chuang YY, Hung IJ, Yang CP, et al. Cefepime versus ceftazidime as empiric
monotherapy for fever and neutropenia in children with cancer. Pediatr Infect Dis J
2002;21:203-9
[Cefepime appears to be as effective & safe as ceftazidime for empiric treatment of
febrile episodes in neutropenic pediatric cancer patients.]
Bruckner LB, Korones DN, Karnauchow T, et. al. High incidence of penicillin
resistance among α-hemolytic streptococci isolated from the blood of children with
cancer. J Pediatr 2002;140:20-6
[Blood culture isolates of alpha-hemolytic streptococci obtained from children with
cancer are frequently resistant to β-lactam antibiotics. Clinically relevant AHS isolates
should be tested for antibiotic susceptibility & β-lactam antibiotics may not be optimal
empiric therapy for fever & neutropenia in children with cancer who have a high risk of
AHS infections.]
Haslam DB. Managing the child with fever and neutropenia in an era of increasing
microbial resistance. J Pediatr 2002;140:5-7 [Laboratory investigations include a
complete blood cell count, culture of urine, and cultures of blood obtained from a
3
Guideline for ED Management of Fever & Neutropenia in Children
peripheral vein and indwelling catheters. Comparison of quantitative colony counts from
blood cultures from these 2 sites may distinguish catheter-associated infection from
another source. Automated blood culture systems currently in use will detect most fungi
and anaerobic bacteria. Nevertheless, in the setting of profound neutropenia and
compromised mucosal surfaces, it is advisable to culture blood specifically for anaerobic
bacteria and fungi. In certain instances, imaging studies such as CXR, ultrasonography,
CT, or MRI of the abdomen, sinuses, or other sites may be indicated, particularly if fever
is prolonged and no apparent source is identified. Empiric ceftazidime plus an
aminoglycoside is one regimen widely used in the treatment of children with fever and
neutropenia. Previously, gram-negative organisms accounted for the majority of cases of
septicemia in neutropenic children. Recent studies demonstrate the ascension of grampositive organisms. Among the most common isolates, coagulase-negative staphylococci
and α-hemolytic streptococci (AHS) account for a large proportion of isolates.
Coagulase-negative staphylococcal bacteremia usually arises from contaminated
intravascular catheters. AHS, often referred to as viridans streptococci, reside
predominantly in the oropharynx and gastrointestinal tract. Damage to mucosal surfaces
that often occurs during chemotherapy provides a portal of entry for AHS. Despite the
lack of classic virulence factors, these organisms are sometimes associated with
fulminant infections. Resistance to β-lactam antibiotics among AHS results from
alterations in penicillin-binding proteins rather than from production of a β-lactamase.
Consequently, addition of a β-lactamase inhibitor, such as sulbactam or tazobactam, to a
β-lactam agent would have no effect on AHS susceptibility. Vancomycin is commonly
used to treat serious AHS infections when the isolate is known to be β-lactam resistant
because no other antibiotic available currently has predictable activity against such
organisms. Although some studies demonstrated a higher treatment failure rate among
patients infected with AHS who did not receive empiric vancomycin compared with
those who did, overall mortality rates were not different. These observations are
considered in the context of emerging vancomycin resistance among some gram-positive
organisms, particularly enterococci. It should be recalled that < 20% patients with febrile
neutropenia will have documented bacteremia; of these, approximately 25% will be
caused by AHS. With the resistance rates presented here, approximately 1 of 40 children
with fever and neutropenia could be expected to have bacteremia as a result of β-lactamresistant AHS. Unfortunately, some of these cases will be fulminant and fatal. However,
initial therapy with vancomycin by no means guarantees of a cure. Two cases presented
by Bruckner et al.highlight the fact that blood cultures may remain positive for AHS, or
infection may relapse, despite vancomycin therapy. A study by Marron et al. reported
that, among 8 patients with serious AHS bacteremia who were treated empirically with
vancomycin, 5 died. Guidelines for the empiric use of vancomycin that were published 5
years ago by the Infectious Disease Society of America remain valid.] They suggest that
only select patients receive vancomycin as part of their initial therapy. Indications include
(1) clinically obvious and serious catheter-related infections, (2) substantial mucosal
damage, (3) known colonization with β-lactam resistant Streptococcus pneumoniae or
Staphylcoccus aureus, (4) growth of a gram-positive organism from the blood (pending
identification and susceptibility testing), and (5) hypotension or other evidence of
cardiovascular dysfunction. On the basis of the data presented by Bruckner et al. recent
treatment with systemic antibiotics might be an additional consideration.]
4
Guideline for ED Management of Fever & Neutropenia in Children
5
Guideline for ED Management of Fever & Neutropenia in Children