Download Management Of Fever And Suspected Infection In Pediatric Patients

Management Of Fever
And Suspected Infection
In Pediatric Patients With
Central Venous Catheters
The use of indwelling central venous catheters is essential for pediatric patients who require hemodialysis, parenteral nutrition, chemotherapy, or other medications. Fever is a common chief complaint in
the emergency department, and fever in a patient with a central venous catheter may be related to a common cause of fever, or it may be
due to a catheter-associated bloodstream infection. Catheter-associated bloodstream infections may also lead to additional complications
such as sepsis, septic shock, or septic complications including suppurative thrombophlebitis, endocarditis, osteomyelitis, septic emboli,
and abscesses. Early resuscitation as well as timely and appropriate
antibiotic therapy have been shown to improve outcomes. This issue
focuses on the approach to fever in pediatric patients with central venous catheters and the management and disposition of patients with
possible catheter-associated bloodstream infections.
Alson S. Inaba, MD, FAAP
Associate Professor of Pediatrics,
University of Hawaii at Mãnoa
John A. Burns School of Medicine,
Division Head of Pediatric
Ari Cohen, MD
Emergency Medicine, Kapiolani
Chief of Pediatric Emergency Medicine
Medical Center for Women and
Services, Massachusetts General
Children, Honolulu, HI
Hospital; Instructor in Pediatrics,
Harvard Medical School, Boston, MA
Madeline Matar Joseph, MD, FAAP,
Associate Editor-in-Chief
FACEP Marianne Gausche-Hill, MD, FACEP,
Professor of Emergency Medicine
Vincent J. Wang, MD, MHA
FAAP
and Pediatrics, Chief and Medical
Associate Professor of Pediatrics,
Professor of Clinical Medicine,
Director, Pediatric Emergency
Keck School of Medicine of USC;
David Geffen School of Medicine
Medicine Division, University of
Associate Division Head, Division
at UCLA; Vice Chair and Chief,
Florida Medical School-Jacksonville,
of Emergency Medicine, Children's
Division of Pediatric Emergency
Jacksonville, FL
Hospital Los Angeles, Los Angeles,
Medicine, Harbor-UCLA Medical
CA
Center, Los Angeles, CA
Stephanie Kennebeck, MD
Associate Professor, University of
Michael J. Gerardi, MD, FAAP,
Editorial Board
Cincinnati Department of Pediatrics,
FACEP, President
Cincinnati, OH
Jeffrey R. Avner, MD, FAAP Associate Professor of Emergency
Professor of Clinical Pediatrics
Medicine, Icahn School of Medicine Anupam Kharbanda, MD, MS
and Chief of Pediatric Emergency
at Mount Sinai; Director, Pediatric
Research Director, Associate
Medicine, Albert Einstein College
Emergency Medicine, Goryeb
Fellowship Director, Department
of Medicine, Children’s Hospital at
Children's Hospital, Morristown
of Pediatric Emergency Medicine,
Montefiore, Bronx, NY
Medical Center, Morristown, NJ
Children's Hospitals and Clinics of
Adam E. Vella, MD, FAAP
Associate Professor of Emergency
Medicine, Pediatrics, and Medical
Education, Director Of Pediatric
Emergency Medicine, Icahn School
of Medicine at Mount Sinai, New
York, NY
Steven Bin, MD
Associate Clinical Professor
of Emergency Medicine and
Pediatrics, UCSF School of
Medicine; Medical Director, Division
of Pediatric Emergency Medicine,
UCSF Benioff Children's Hospital,
San Francisco, CA
Richard M. Cantor, MD, FAAP,
FACEP
Professor of Emergency Medicine
and Pediatrics, Director, Pediatric
Emergency Department, Medical
Director, Central New York Poison
Control Center, Golisano Children's
Hospital, Syracuse, NY
Authors
Courtney Brennan, MD
Fellow, Division of Emergency Medicine, Children’s Hospital Los
Angeles, Los Angeles, CA
Vincent J. Wang, MD, MHA
Associate Professor of Pediatrics, Keck School of Medicine of
USC; Associate Division Head, Division of Emergency Medicine,
Children’s Hospital Los Angeles, Los Angeles, CA
Peer Reviewers
Abstract
Editor-in-Chief
December 2015
Volume 12, Number 12
Ilene Claudius, MD
Associate Professor of Emergency
Medicine, Keck School of Medicine
of USC, Los Angeles, CA
Minnesota, Minneapolis, MN
Sandip Godambe, MD, PhD
Vice President, Quality & Patient
Tommy Y. Kim, MD, FAAP, FACEP
Safety, Professor of Pediatrics and
Associate Director of Emergency
Emergency Medicine, Attending
Medicine and Pediatrics, Loma
Physician, Children's Hospital of the
Linda University Medical Center and
King's Daughters Health System,
Children’s Hospital, Loma Linda, CA
Norfolk, VA
Melissa Langhan, MD, MHS
Ran D. Goldman, MD
Associate Professor of Pediatrics,
Professor, Department of Pediatrics,
Fellowship Director, Director of
University of British Columbia;
Education, Pediatric Emergency
Co-Lead, Division of Translational
Medicine, Yale School of Medicine,
Therapeutics; Research Director,
New Haven, CT
Pediatric Emergency Medicine, BC Robert Luten, MD
Children's Hospital, Vancouver, BC, Professor, Pediatrics and
Canada
Emergency Medicine, University of
Florida, Jacksonville, FL
Shruti Kant, MBBS, FAAP
Assistant Professor of Pediatric Emergency Medicine, Department
of Emergency Medicine, University of California San Francisco, San
Francisco, CA
Ron L. Kaplan, MD
Associate Professor, Department of Pediatrics, University of
Washington School of Medicine; Emergency Department, Seattle
Children’s Hospital, Seattle, WA
CME Objectives
Upon completion of this article, you should be able to:
1.
Describe the presentation of infections related to central
venous catheters.
2. Identify common organisms known to cause catheter-associated
bloodstream infections in different patient populations.
3. Determine appropriate initial empiric antibiotic therapy for
patients with central venous catheters presenting with fever.
4. Recognize the signs and symptoms of sepsis in patients with
a central venous catheter who present with fever and provide
appropriate and timely therapies.
Prior to beginning this activity, see “Physician CME Information”
on the back page.
Garth Meckler, MD, MSHS
AAP Sponsor
Associate Professor of Pediatrics,
Martin I. Herman, MD, FAAP, FACEP
University of British Columbia;
Division Head, Pediatric Emergency Sacred Heart Children's Hospital,
Pensacola, FL; Florida State
Medicine, BC Children's Hospital,
University School of Medicine,
Vancouver, BC, Canada
Pediatric Residency Department,
Joshua Nagler, MD
Tallahassee, FL
Assistant Professor of Pediatrics,
Harvard Medical School; Fellowship International Editor
Director, Division of Emergency
Lara Zibners, MD, FAAP
Medicine, Boston Children’s
Honorary Consultant, Paediatric
Hospital, Boston, MA
Emergency Medicine, St Mary's
James Naprawa, MD
Associate Clinical Professor
of Pediatrics, The Ohio State
University College of Medicine;
Attending Physician, Emergency
Department, Nationwide Children’s
Hospital, Columbus, OH
Hospital, Imperial College Trust;
EM representative, Steering Group
ATLS®-UK, Royal College of
Surgeons, London, England
Pharmacology Editor
James Damilini, PharmD, MS, BCPS
Clinical Pharmacy Specialist,
Joshua Rocker, MD
Emergency Medicine, St. Joseph's
Assistant Professor of Emergency
Hospital and Medical Center,
Medicine and Pediatric, Hofstra
Phoenix, AZ
North Shore-LIJ School of Medicine,
Hempstead, NY; Associate Director, Quality Editor
Division of Pediatric Emergency
Medicine, Cohen Children's Medical Steven Choi, MD
Medical Director of Quality, Director
Center, New Hyde Park, NY
of Pediatric Cardiac Inpatient
Steven Rogers, MD
Services, The Children’s Hospital at
Assistant Professor, University of
Montefiore; Associate Vice President,
Connecticut School of Medicine,
Montefiore Network Performance
Attending Emergency Medicine
Improvement; Assistant Professor of
Physician, Connecticut Children's
Pediatrics, Albert Einstein College of
Medical Center, Hartford, CT
Medicine, Bronx, NY
Christopher Strother, MD
CME
Editor
Assistant Professor, Emergency
Medicine, Pediatrics, and Medical
Deborah R. Liu, MD
Education; Director, Undergraduate
Assistant Professor of Pediatrics,
and Emergency Department
Keck School of Medicine of USC;
Simulation; Icahn School of Medicine
Division of Emergency Medicine,
at Mount Sinai, New York, NY
Children's Hospital Los Angeles,
Los Angeles, CA
Case Presentations
resuscitative measures, has been studied extensively
and has been shown to improve outcomes in febrile neutropenic patients with indwelling central
catheters.1 The time to antibiotic therapy has been
consistently used as a quality-of-care measure in
this patient population.1,2 Although less-studied
in other pediatric populations relying on CVCs, a
regular complication in these patients remains the
occurrence of CA-BSI. Sepsis syndrome remains a
leading cause of morbidity and mortality in pediatric patients, and the Surviving Sepsis Campaign
(www.survivingsepsis.org) recommends initiation
of empiric antibiotic therapy within 1 hour of the
recognition of severe sepsis or septic shock in both
adult and pediatric patients.
An 8-year-old boy with a history of standard-risk acute
lymphoblastic leukemia presents to the ED with a fever.
He has a port central line and is currently undergoing
the delayed intensification phase of chemotherapy. He last
received chemotherapy 1 day prior to presentation. He also
reports a headache and a cough. Upon examination, he is
febrile to 39.2ºC, with a heart rate of 120 beats/min and
blood pressure of 108/60 mm Hg. He is breathing comfortably and has an oxygen saturation of 99% on room air. You
consider what initial laboratory workup you might need…
A 4-year-old girl with a history of gastroschisis
requiring intestinal resection that resulted in short gut
syndrome presents with a history of fever, vomiting, and
diarrhea. She is dependent upon total parenteral nutrition, which is delivered through a Broviac® catheter. She
has a history of multiple previous line infections, including a recent MRSA line infection. On examination, her
temperature is 38.2°C, and she has a heart rate of 105
beats/min and blood pressure of 100/55 mm Hg. You
wonder what initial laboratory testing and imaging you
should consider, and what the appropriate disposition for
this patient should be…
Critical Appraisal Of The Literature
An online search for literature from 1980 to the present was performed using the Pubmed and MEDLINE® databases. Search terms included fever, central
venous catheter, and infection. More than 6000 articles
were found using the search terms and included
case reports, review articles, and prospective and
retrospective studies. This was narrowed by limiting the results to studies involving children aged
0 to 18 years, and articles published in English. A
search on Ovid® produced 662 articles, which were
analyzed and further refined to 73 relevant articles.
Two clinical practice guidelines were also included
in the results. A search of the Cochrane Database of
Systematic Reviews was also conducted. There is a
significant amount of literature on fever or infection
with a CVC in the pediatric hematology-oncology
population; however, there is a relative paucity of literature specific to other patient populations, such as
pediatric patients on dialysis, patients with intestinal
failure, patients dependent upon parenteral nutrition, and other subsets commonly requiring longterm central venous access. Very little information is
available on the evaluation and acute management
of fever in patients with a CVC in the ED.
Introduction
Fever is a common chief complaint of pediatric patients presenting to the emergency department (ED),
and patients with a central venous catheter (CVC)
may also have common causes of fever similar to
children without pre-existing medical conditions.
While these common causes of fever may occur in
patients with CVCs, it is imperative that emergency
clinicians investigate all episodes of fever for catheter-associated bloodstream infections (CA-BSI), and
initiate prompt and appropriate antibiotic therapy if
catheter-associated infection is suspected.
The use of an indwelling CVC is essential in
pediatric patients who require hemodialysis, parenteral nutrition, frequent blood draws, frequent blood
product transfusions, or long-term intravenous
medications (such as antibiotics or chemotherapeutics). Although essential to the treatment of these
patients, there are several complications that may
arise with the ongoing use of CVCs. In addition to
catheter dysfunction, thrombosis, and embolization,
patients with a CVC may also experience infection at
the insertion site, the tunneled portion of the catheter, the subcutaneous pocket of a totally implanted
intravascular device (a pocket infection), or within
the catheter itself. The indwelling catheter provides
a portal of entry for bacteria (and other organisms),
and renders these patients susceptible to the development of a CA-BSI and the potential for progression to overwhelming infection and sepsis.
The rapid recognition and triage of these patients, with subsequent initiation of antibiotics and
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Etiology And Pathophysiology
There are several different types of indwelling CVCs
used in pediatric patients who have a need for
long-term vascular access. These catheters are either
peripherally inserted central catheters (PICCs), surgically placed central catheters, or totally implanted
devices or ports. Surgically placed catheters include
tunneled or nontunneled partially implanted catheters. (See Table 1, page 3.) The choice of catheter
used in each patient is based upon the length of
time that the catheter is needed, the reason for its
use, and patient-related factors such as age, size, or
patient and family preferences. Complications of the
long-term use of all types of catheters include mal2
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function, line fracture or leakage, and thrombosis,
as well as infectious complications such as tunnel or
pocket infections, CA-BSI, metastatic infections, and
sepsis.3,4,5
The terms catheter-related bloodstream infection
(CR-BSI) and CA-BSI are often used interchangeably
by clinicians. However, they differ in the degree of
proof of infection that is required for the diagnosis.
related to another source) or clinical sepsis in the
presence of an intravascular device.10,11 In pediatric
patients, a diagnosis of CA-BSI is more likely since
peripheral blood cultures are not often obtained.
Since a confirmed diagnosis requires time for cultures to grow, it must be assumed that the catheter
is the source of fever in these patients in order to
provide timely treatment.
CA-BSIs remain a significant cause of morbidity
and mortality in pediatric patients. The incidence
of CA-BSIs varies and is based on several catheterand patient-related factors. Catheter-related factors
include the catheter type, the number of catheter
lumens, the location of insertion, and the duration
of catheter placement.13 Factors associated with
early infection after placement of a CVC include the
presence of neutropenia at the time of CVC insertion
and failure to provide perioperative antibiotics at the
time of insertion.14
Catheter-Related Bloodstream Infection
CR-BSI is a term used for research purposes, and is
defined by a positive peripheral culture and either a
positive culture from the catheter tip or differences
in the time between the growth between catheter
and peripheral culture specimens. Additionally, 1
of the following must also be present: (1) a positive semiquantitative culture (> 15 colony-forming
units/catheter segment); (2) a positive quantitative
blood culture (> 103 colony-forming units/catheter
segment) of the same organism; (3) paired peripheral
and catheter quantitative blood cultures that have
a ratio of > 3:1 colony-forming units/mL of blood
(catheter vs peripheral); or (4) a differential time to
positivity of growth of an organism from the sample
drawn from the catheter hub that is at least 2 hours
before growth detected from the peripheral vein.6-9
Association Of Catheter Type And Infectious
Complications
Several studies have examined the association of
catheter type and rate of infectious complications.
Of the various catheters used for central access,
totally implanted catheters (ports) are associated
with the lowest risk of infection. A study examining both CVC- and patient-related factors influencing the risk of infectious complications in pediatric
patients receiving chemotherapy demonstrated that
the type of CVC was significantly associated with
the incidence of bloodstream infection with a hazard
ratio (the chance of a bloodstream infection occurring) for tunneled externalized catheters and peripherally inserted central catheters of 2.16 and 1.43,
respectively, when compared to totally implanted
devices.15 Another study by Newman et al compared infection rates between Hickman® catheters
and implanted ports in pediatric cancer patients. Of
the 178 CA-BSIs in 93 patients, more infections were
recorded among patients with Hickman® catheters
than ports.16 Similar results were found in the study
by Adler et al that compared infection rates between
Hickman® catheters and implanted ports. The study
showed that infectious complications were more
frequent in the Hickman® catheter group, and that
the time from catheter insertion to the first catheterassociated infection was shorter in patients with
Hickman® catheters than with ports.17 In another
retrospective cohort study, the risk of bacteremia in
patients with external catheters (such as Hickman®
or Broviac® catheters) was 4 times that of implanted
catheters.18
Of the surgically placed partially implanted
devices such as Hickman® or Broviac® catheters,
there is evidence that catheters with multiple lumens
are associated with the highest infection risk. In an
observational study comparing complication rates
Catheter-Associated Bloodstream Infection
A CA-BSI is a primary bloodstream infection (any
laboratory-confirmed bloodstream infection not
Table 1. Types Of Central Venous
Catheters6,10-12
Catheter Type
Description
Temporary central
catheters
• Rapid bedside placement
• Can have single or multiple lumens
• Intended for short-term use in inpatient setting only
• Highest infection risk
Peripherally inserted
central catheters
• Used for short- or long-term access
• Can be placed at bedside
• Introduced into a peripheral vein and
threaded to terminate in a central
location
Long-term tunneled
central venous
catheters (Broviac®,
Hickman®,
Groschong®,
NeoStarTM)
• Surgically placed, tunneled portion
under skin with lumen exiting from
skin
• Catheter has a cuff that sits under
the skin and helps keep the catheter
in place
• Can have single lumen or multiple
lumens
Totally implanted ports
• Surgically placed
• Entirely buried under the skin
• Can only be accessed by a specific
Huber needle
• Lowest infection risk
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between double- and single-lumen Hickman® and
Broviac® catheters, as well as pressure-activated
safety valve catheters inserted in pediatric oncology
patients, double-lumen catheters had the highest
rate of reported infectious complications among all
catheters, with 56 out of 114 complications.7
Specific patient populations must also be considered when thinking about common pathogens
causing infection. (See Table 2.) When considering patients who require central venous access for
prolonged nutritional therapy, particularly due to
intestinal failure, gram-negative enteric organisms
are more common cause of infection. Common
pathogens detected in this population with varying frequency include Escherichia coli, coagulasenegative staphylococci, Klebsiella pneumoniae, and
Enterococcus species.27-30 Although all pediatric
patients with indwelling CVCs are at increased risk
for polymicrobial infections, patients with underlying gastrointestinal pathology and patients who are
dependent upon parenteral nutrition appear to have
the greatest risk.31-32 In a review of studies looking at
CA-BSI in pediatric hemodialysis patients, the most
common pathogens are S aureus, coagulase-negative
staphylococci, enterococci, gram-negative bacteria,
mycobacteria, and Candida species.33,34 In pediatric
oncology patients, gram-positive organisms (specifically Staphylococcus epidermidis, coagulase-negative
staphylococci, and S aureus) are most common, and
account for up to 70% of proven bloodstream infections. However, gram-negative organisms continue
to play a role in disease in this population with P
aeruginosa an important pathogen to consider in
neutropenic oncology patients.20 Children who have
a history of multiple CA-BSIs or a history of prolonged antimicrobial therapy are at increased risk
for antimicrobial-resistant organisms.
Other Factors Affecting Infection Rate
In addition to catheter-related factors, a number of
additional factors have been noted to increase the
infection rate. These include younger age of the
patient (< 3 years), use of the catheter for parenteral
nutrition or chemotherapy, lower body weight (< 8
kg), or the presence of neutropenia or patients who
have undergone stem cell transplantation.19-26
Infectious Pathogens
According to the 2009 Infectious Diseases Society of
America Clinical Practice Guidelines for the Diagnosis and Management of Intravascular CatheterRelated Infections, the most common pathogens
causing CA-BSI from surgically implanted catheters
and peripherally inserted CVCs in both children and
adults are coagulase-negative staphylococci, Staphylococcus aureus, enteric gram-negative bacilli, and
Pseudomonas aeruginosa. In the pediatric population,
S aureus and coagulase-negative staphylococci were
found to be the most common pathogens overall.6
Table 2. Common Organisms Causing
Infection In Patients With Central Venous
Catheters6,20,27-34
Patient Population
Common Micro-organisms
Patients with surgically
implanted or peripherally
inserted central venous
catheters
• Coagulase-negative staphylococci*
• Staphylococcus aureus*
• Enteric gram-negative bacilli
• Pseudomonas aeruginosa
Intestinal failure/parenteral nutrition-dependent
patients
• Escherichia coli
• Coagulase-negative staphylococci
• Klebsiella pneumoniae
• Enterococcus
• Polymicrobial infections
Hemodialysis patients
• Staphylococcus aureus
• Coagulase-negative staphylococci
• Enterococci
• Gram-negative bacteria
• Mycobacteria
• Candida species
Oncology patients
• Gram-positive organisms
(Staphylococcus epidermidis,
coagulase-negative staphylococci, Staphylococcus aureus)
• Pseudomonas aeruginosa
Pathogenesis
The pathogenesis of CVC-related infection is complex. In order for a micro-organism to cause infection,
it must gain access to the extraluminal or intraluminal
surface of the catheter. Extraluminal contamination
is often due to common skin pathogens that migrate
from the skin to the subcutaneous tract. They are
often introduced during placement or manipulation
of the catheter, and this method of contamination is
the typical cause of catheter-related infection in the
first month after catheter placement.35 Intraluminal
contamination can occur when there is colonization of
the catheter hub, particularly by common skin organisms. The catheter hub is a usual source of infection
in long-term catheters and in tunneled catheters, in
particular. The failure to use aseptic techniques during catheter placement or when accessing the catheter
is associated with a higher risk of infection.34,35 More
rarely, seeding of the catheter from a distant source of
infection or from a contaminated infusate may cause
catheter contamination.36
Once a micro-organism gains access to the
catheter, it can cause local infections, such as exit site
infections, tunnel infections, or pocket infections.
However, once released into the bloodstream, this
pathogen invasion activates a cascade of events that
*Most common in pediatric patients
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can cause a wide range of symptoms including fever,
tachycardia, tachypnea, vasodilation, and, in the
most severe cases, circulatory collapse, end-organ
damage, and death.37
of a totally implanted intravascular device. These infections typically present with tenderness, erythema,
and induration over the pocket, and the pockets can
often rupture and drain.6,38
Systemic Infections
Differential Diagnosis
In many cases of a CA-BSI, fever may be the only presenting symptom. However, in addition to fever, some
patients with presumed CA-BSI also present with
changes in vital signs or laboratory values, meeting the
criteria for sepsis. In the pediatric population, sepsis
can be defined as a proven or suspected infection in the
presence of systemic inflammatory response syndrome
(SIRS). Pediatric SIRS criteria include at least 2 of the
following: (1) temperature > 38.5°C or < 36°C; (2)
changes in heart rate manifested as tachycardia
> 2 standard deviations above normal for patient age
or bradycardia in patients aged < 1 year; (3) tachypnea with respiratory rate > 2 standard deviations
above normal for patient age; and (4) leukocyte count
elevated or depressed for age or the presence of > 10%
immature neutrophils. (See Table 3.)
The progression to severe sepsis is defined as
sepsis with evidence of cardiovascular organ dysfunction, acute respiratory distress syndrome, or
evidence of organ dysfunction of ≥ 2 systems. Septic
shock is sepsis with evidence of cardiovascular
dysfunction (usually hypotension), unexplained
acidosis, elevated serum lactate, core-to-peripheral
temperature gap > 3ºC, prolonged capillary refill
time, or oliguria.39 Complications of sepsis can also
Children presenting to the ED with fever and a CVC
must be evaluated for a catheter-related source of
infection. Catheter-associated infections may be local
or systemic.
Local Infections
Local infections at the catheter site include phlebitis,
exit site infections, tunnel infections, and pocket infections. Common presenting signs include induration, erythema, tenderness, fluctuance, and purulent drainage at the catheter site. Fever is often an
associated symptom in local catheter site infections;
however, it is not always present.
Phlebitis presents as erythema, induration, and/
or tenderness along the tract of a catheterized vein.
Exit site infections present with erythema, induration,
and/or tenderness within 2 cm of the catheter exit
site, and may be associated with fever or purulent
drainage from the exit site. A tunnel infection also
presents with tenderness, erythema, and/or induration that is > 2 cm from the catheter exit site along
the subcutaneous tract of a tunneled catheter (such
as a Hickman® or Broviac® catheter). Pocket infections contain infected fluid in a subcutaneous pocket
Table 3. Types Of Systemic Infections6,10,39
Type of Infection
Characteristics
Catheter-related bloodstream infection
Bacteremia or fungemia in a patient who has an intravascular device, > 1 positive blood culture result obtained from the
peripheral vein, and no apparent source for bloodstream infection other than the catheter itself, with at least 1 of the
following:
• A positive semiquantitative culture (> 15 colony-forming units/catheter segment)
• A positive quantitative blood culture (> 103 colony-forming units/catheter segment) of the same organism
• Paired peripheral and catheter quantitative blood cultures that have a ratio of > 3:1 colony-forming units/mL of blood
(catheter vs peripheral)
• A differential time to positive growth of an organism from the sample drawn from the catheter hub that is at least 2
hours before growth detected from the peripheral vein
Sepsis
• SIRS in the setting of proven or suspected infection
• SIRS criteria (must have 2 of 4 criteria, and 1 must be abnormal temperature or leukocyte count):
l
l
l
l
Core temperature > 38.5°C or < 36°C
Tachycardia (mean HR > 2 standard deviations above normal for age in absence of another explanation) or
bradycardia (mean HR < 10th percentile for age) in children aged < 1 year
Mean respiratory rate > 2 standard deviations above mean for age or need for mechanical ventilation
Leukocyte count elevated or depressed for age (not chemotherapy-induced) or presence of > 10% immature neutrophils
Severe sepsis
Sepsis plus 1 of the following:
• Cardiovascular organ dysfunction
• Acute respiratory distress syndrome
• Dysfunction of ≥ 2 organs
Septic shock
Sepsis and evidence of cardiovascular organ dysfunction (ie, unexplained acidosis, elevated serum lactate, core-toperipheral temperature gap > 3ºC, prolonged capillary refill time, or oliguria)
Abbreviations: HR, heart rate; SIRS, systemic inflammatory response syndrome.
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Prehospital Care
arise in patients with CA-BSI and include suppurative thrombophlebitis, endocarditis, septic thromboemboli, osteomyelitis, and abscesses.
While there are several infectious complications
related to the presence of a catheter, many patients
with a CVC presenting with fever will not have a
catheter-related infection, and the information obtained on history and physical examination will guide
the differential diagnosis. (See Table 4.)
Many patients with a CVC presenting with fever
will have had some contact with a medical provider prior to presentation to the ED. Patients
being transported via emergency medical services should be assessed immediately. Vital signs
should be closely monitored, and careful attention should be paid to the airway, breathing, and
circulation in these patients. Supplemental oxygen
therapy may be provided in the setting of clinical signs of sepsis or in the setting of respiratory
distress or oxygen desaturation.
In patients with signs of sepsis or severe sepsis,
additional intravenous access may be obtained if
needed, and fluid resuscitation should begin prior to
arrival to the ED. According to the Pediatric Advanced Life Support (PALS) guidelines, fluid resuscitation should begin promptly at the first recognition
of sepsis, with a fluid bolus of 20 mL/kg of isotonic
fluids (typically normal saline) given over 5 to 10
minutes. Up to 60 mL/kg can be given as needed
within the first hour. Out-of-hospital care has been
shown to improve inhospital processes and shorten
the length of time to the initiation of antibiotics and
intravenous fluids in the setting of patients presenting
in sepsis or severe sepsis.40,41
Table 4. Differential Diagnosis For Fever In
Patients With A Central Venous Catheter6,10,39
Local Catheter-Related Causes
• Phlebitis
• Exit site infection
• Tunnel infection
• Pocket infection
Systemic Catheter-Related Causes
• Catheter-related bloodstream infection
• Sepsis
• Severe sepsis
• Septic shock
• Endocarditis
• Abscess
• Septic thromboembolism
• Osteomyelitis
Other Causes of Fever Not Associated With the Central Venous
Catheter
• Central Nervous System
Emergency Department Evaluation
Meningitis
History
l Encephalitis
• Head, Ears, Eyes, Nose, and Throat
l A thorough history should be obtained, including
evaluation of the onset, duration, and maximum
height of the fever. Any prior administration and
timing of antipyretics should be noted. History of
erythema, tenderness, fluctuance, induration, or
drainage at the catheter site should be elicited.6 Ask
about the caregivers’ perception of the child’s behavior in order to detect any alterations from the child’s
baseline. Additional relevant symptoms that may
help guide management should be ascertained by a
complete review of systems.
It is important to know the type of CVC a
patient has and when the catheter was placed. In
patients who are immunocompromised and have
an indwelling central catheter for the delivery of
chemotherapy, ask when the patient last received
chemotherapy and what type of chemotherapy was
given. Certain chemotherapy protocols are more
myelosuppressive, placing the patient at greater
risk for neutropenia and overwhelming infection.42
In patients known to be neutropenic, the duration
of neutropenia is helpful to know, as the length of
neutropenia correlates directly with risk of infection.43,44 The patient’s type of malignancy is relevant,
as leukemia and lymphoma—in contrast to solid
tumors—have been identified as risk factors for
bacteremia.44,45 A history of chills or emesis may also
Acute otitis media
l Pharyngitis
l Tonsillitis
l Sinusitis
l Conjunctivitis
l Lymphadenitis
l Gingivostomatitis
• Respiratory
l Pneumonia
l Upper respiratory tract infection
l Croup
• Gastrointestinal
l Viral or bacterial gastroenteritis
l Appendicitis
l Neutropenic enterocolitis
l Perirectal abscess
• Genitourinary
l Urinary tract infection/pyelonephritis
• Skin
l Abscess
l Cellulitis
l Erysipelas
• Other
l Drug reaction
l Systemic viral infection
l Kawasaki disease
l Copyright © 2015 EB Medicine. All rights reserved.
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suggest bacteremia in febrile neutropenic patients.46
Review the patient’s past medical history for
previous central line infections, and what pathogens
grew in the patient’s previous cultures, if known. In
patients who report a history of recurrent central line
infections, review any available microbiology results
to identify multidrug-resistant organisms that may
have grown in the past, especially recently. Relevant
family history includes recurrent skin abscesses, infections, or known methicillin-resistant Staphylococcus
aureus (MRSA) colonization or infections.
In some instances of severe neutropenia, perirectal
abscess formation may not occur due to the low
neutrophil count, and, therefore, tenderness may be
the only sign of pathology in these patients.
In all patients with a CVC presenting with fever,
serial examinations, including frequent measurement of vital signs, are essential to evaluate for any
new findings, clinical changes, or evidence of clinical
deterioration.
Physical Examination
Blood Culture
Diagnostic Studies
A complete set of vital signs (temperature, heart rate,
blood pressure, respiratory rate, and oxygen saturation) should be obtained on every patient with a
CVC presenting with fever. According to the International Pediatric Sepsis Consensus Conference,
fever within 4 hours prior to arrival documented by
a reliable source should be considered a true fever
in pediatric patients who are afebrile on arrival.39
Any vital signs meeting criteria for SIRS should be
noted, and patients with these criteria at presentation should be evaluated immediately.
A thorough examination is essential to uncover
any potential source of fever. Look for meningeal
signs and changes or alterations from baseline mental
status. A thorough head, eyes, ears, nose, and throat
examination includes examination of the tympanic
membranes for signs of acute otitis media; looking
inside the oropharynx for oral lesions, erythema, or
exudates, and the lips for mucosal changes; examining the eyes for signs of conjunctivitis; and evaluating for sinus tenderness. Look for signs of increased
work of breathing, and auscultate for any differences
on lung examination that may suggest pneumonia,
especially if the oxygen saturation level is low. Auscultation of the heart is also essential, and evidence
of any new murmurs should be noted. Examine
the abdomen for signs that may suggest pathology
such as distension, absent bowel sounds, tenderness, rebound, or guarding. Inspect the catheter site
for surrounding erythema, induration, fluctuance,
or presence of discharge. Pay particular attention to
signs of decreased perfusion such as delayed capillary
refill time, cool extremities, diminished or bounding
peripheral pulses, or changes in mental status.
Neutropenic patients may not mount the same
inflammatory response as other patients. Therefore,
consider investigating further even subtle examination findings in these patients.42 Pay particular
attention to the mucous membranes for signs of
mucositis or skin breakdown, as these place the
patient at greater risk of bacterial translocation.
Abdominal distension or tenderness should prompt
further investigation for neutropenic enterocolitis or
typhlitis. The perirectal area should be inspected for
skin breakdown or evidence of perirectal abscess.
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A blood culture should be obtained prior to the initiation of antibiotic therapy in all patients with a CVC
presenting with fever. However, this should not significantly delay antibiotic therapy. The Infectious Diseases Society of America recommends paired blood
samples from both a catheter lumen and a peripheral
vein. In a large prospective study of pediatric oncology patients with a CVC presenting with fever, 17% of
true bloodstream infections were diagnosed in a culture from a peripheral vein when the paired culture
from the CVC was negative.47 A similar retrospective
study at a single institution also evaluated episodes
of bacteremia that were diagnosed solely on the basis
of peripheral culture. In this study, 318 episodes of
bloodstream infections were included, of which 228
were classified as true bloodstream infections, and the
remaining 90 cases were considered contaminants. Of
the true bloodstream infections, 28 cases were detected solely from the peripheral blood culture when
CVC and peripheral cultures were obtained within 24
hours of each other.48
Despite evidence to suggest the utility of both
CVC and peripheral blood cultures, obtaining a peripheral blood sample is not always routine in many
institutions, as it is deemed to be unpleasant for the
patient. In cases when it is not possible to obtain a
peripheral venous sample, 2 or more blood samples
should be obtained from different catheter lumens
if more than 1 lumen is present. When the colony
count for the blood sample drawn from 1 lumen is at
least 3-fold greater than the other lumen, the results
may be considered a possible CR-BSI.6,49
It is important to ensure that an adequate sample
of blood is drawn from the patient. Although there is
no specific quantity of blood recommended to ensure
an adequate sample, a study conducted by Isaacman
et al showed that obtaining a single small-volume
sample failed to detect bacteremia in a significant
proportion of children.50
Complete Blood Count
While the diagnosis of CA-BSI or CR-BSI is based
upon culture results, a complete blood count (CBC)
with differential should be obtained. Leukocytosis
or leukopenia for age is 1 of the SIRS criteria and is
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Other Laboratory Testing
often routinely used as a diagnostic tool in the setting of concern for severe infection. In addition, any
patient who is potentially immunocompromised or
who is receiving chemotherapy should have a CBC
with differential ordered to determine whether the
patient is neutropenic (according to thresholds set by
the institution) from their ongoing treatment. A CBC
is also relevant in any patient presenting with signs
of severe sepsis or septic shock, as blood products
(including packed red blood cells and platelets) may
be required in the initial resuscitation.
Although not directly predictive of infection, additional laboratory testing may assist in patient management and should be considered, particularly in the
setting of sepsis. Urinalysis and culture are also recommended in neutropenic patients as long as a cleancatch urine sample can be obtained prior to initiation
of antibiotic therapy.49 In the presence of signs of local
catheter site infection, a culture of any purulent drainage from the catheter site should be obtained.6
Many of the patient’s treatment medications
may be nephrotoxic or hepatotoxic. A complete
metabolic panel will evaluate for electrolyte abnormalities as well as kidney and liver dysfunction, as
demonstrated by serum creatinine and transaminase
levels, respectively. Adjustment of antibiotics may be
necessary if renal or hepatic dysfunction is present.
A blood gas with serum lactate level will evaluate
for acidosis and aid in monitoring systemic perfusion. Any additional laboratory studies obtained
should be based upon information gathered on the
history or physical examination.
C-Reactive Protein
C-reactive protein (CRP) is a serum biomarker that is
often measured in the setting of infection or when infection is suspected, and higher levels typically correlate with more-severe infection. CRP is an acute phase
reactant that is released by the liver in the setting of
inflammation within 4 to 6 hours of insult. CRP levels
double every 8 hours and peak around 36 hours.51
Several studies have looked at the diagnostic value
of CRP in the prediction of serious bacterial infection
in pediatric patients. A prospective study by Pulliam
et al looked at the diagnostic properties of CRP in
the setting of clinically undetectable serious bacterial
infection in patients aged 1 to 36 months. The results
of the study showed that CRP was more sensitive
and specific than white blood cell count or absolute
neutrophil count in predicting serious bacterial infection in pediatric patients.52 A systematic review by
Sanders et al looked at the diagnostic accuracy of CRP
in detecting serious bacterial infection or bacterial
versus viral infection in nonhospitalized infants and
children. The results indicate that CRP has moderate
value for ruling out serious bacterial infection but has
minimal value in ruling out all bacterial infections.53
Additionally, the aforementioned studies provide
information regarding the diagnostic utility of CRP
in otherwise healthy patients presenting with fever,
and it is unclear whether the presence of an indwelling catheter or a patient’s underlying disease process
affect the utility of CRP studies.
Imaging Studies
Imaging should be based upon history or physical
examination findings, and should not be routinely
ordered. Consider chest radiographs to evaluate
for pneumonia if any symptoms such as tachypnea,
respiratory distress, abnormal examination findings,
or low oxygen saturations are present. When there
is concern for catheter thrombosis or suppurative
thrombophlebitis, an ultrasound should be obtained.
Identification of suppurative thrombophlebitis is an
indication for timely catheter removal.6,55
In febrile neutropenic patients, abdominal
imaging may be helpful if examination findings are
subtle. When abdominal tenderness is present, consider abdominal radiographs or computed tomography scan to evaluate for neutropenic enterocolitis.
Treatment
Initial Resuscitation
Polymerase Chain Reaction
One study by Schachor-Mayheous et al looked at the
molecular-based diagnosis of bacteremia in the setting of fever with or without neutropenia using the
polymerase chain reaction (PCR) method for early
detection of bacteremia.54 In the 148 blood cultures
evaluated, the PCR method had a 48% sensitivity,
but a 98% specificity for detecting bacteremia when
compared to conventional culture results. The positive and negative predictive values were 86% and
89%, respectively.54 Although not as sensitive as
culture in detecting all episodes of bacteremia, the
study does demonstrate PCR's utility in obtaining
more-timely results and, in the event of a positive
result, allows for the rapid ability to tailor antibiotic
therapy to a specific pathogen.
Copyright © 2015 EB Medicine. All rights reserved.
Initial resuscitation should focus on the patient’s
airway, breathing, and circulation. In the setting of
sepsis or septic shock, oxygen should initially be
provided via nasal cannula to maximize oxygen-carrying capacity. The decision to escalate respiratory
support or to intubate patients within the setting
of sepsis is based on a number of factors, including
increased work of breathing, hypoventilation, and
change in mental status. Therefore, close and continued evaluation of the respiratory status of these
patients is imperative.56,57
Circulatory status should be assessed, and
fluid resuscitation should be initiated if hemodynamic abnormalities are present. Fluid resuscitation should begin within the first 60 minutes,
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according to the PALS guidelines, with boluses
of 20 mL/kg of crystalloid fluids given over 5 to
10 minutes. Boluses should be titrated to reversing hypotension, restoring normal heart rate for
age, improving capillary refill time and peripheral
pulses, increasing urine output, and improving
mental status. Early reversal of hemodynamic
abnormalities in pediatric patients with shock has
been shown to greatly decrease mortality, regardless of the stage of abnormality at the time of
presentation.57,58
between lumens with each dose, if applicable. Routine initiation of antifungal therapy is not indicated in
pediatric patients unless there is high clinical suspicion for fungal infection.6,11,56
Empiric antibiotics should be continued until
culture results and antibiotic susceptibilities are
available. In the event that only 1 blood culture is
obtained, positive results may be difficult to interpret in some cases. For example, coagulase-negative
Staphylococcus is a common skin micro-organism that
is often a contaminant in blood cultures. However,
it can also be pathogenic in patients with a CVC and
cannot be determined to be a contaminant if only
1 blood sample drawn from 1 catheter lumen was
found to be positive. If only 1 blood sample was
drawn initially, a repeat sample should be drawn
for culture, and empiric antibiotics continued while
awaiting culture results.
When there is evidence of local catheter site infection, topical antibiotics may be sufficient if blood
culture results are negative and there is no clinical
concern for systemic infection. In the case of a tunnel
infection or pocket infection, removal of the catheter and administration of systemic antibiotics are
recommended.6,36
Antibiotics
Prompt administration of empiric antibiotic therapy
to a patient with a CVC is critical if bacterial infection is suspected. Time to antibiotic therapy of < 60
minutes has been associated with a lower rate of
adverse outcomes in febrile neutropenic patients.1
The Surviving Sepsis Campaign also recommends
administering empiric antibiotics within 60 minutes
in patients presenting with sepsis. In a large retrospective study, delaying initial antibiotic therapy by
> 3 hours from recognition of severe sepsis or septic
shock was shown to be an independent risk factor
for mortality in pediatric patients.59
The choice of antibiotic therapy should be based
on several factors, including the patient’s underlying medical condition and reason for the CVC,
history of previous positive culture results, and the
institution’s antibiogram and susceptibility patterns.
Empiric therapy with antibiotics having a broad
spectrum of gram-positive and gram-negative effectiveness (such as vancomycin) should be initiated
while awaiting culture results. The International
Pediatric Fever and Neutropenia Guideline Panel
recommends initial monotherapy with either an antipseudomonal beta-lactam or a carbapenem in neutropenic patients deemed to be high risk. In patients
with a history of infection with a multidrug-resistant
organism, a carbapenem should be initiated while
awaiting culture results.47,60 The exact choice of
antibiotic therapy in these patients should be based
upon the local susceptibilities or individual medical
center protocols. The addition of a second gram-negative agent (such as an aminoglycoside or carbapenem) should be reserved for unstable patients. In
patients with a higher likelihood of gram-negative
enteric organisms (such as patients with short gut
syndrome), we recommend consideration of double
antibiotic coverage for gram-negative organisms. In
patients with a history of MRSA infection, skin colonization, or in centers with a high prevalence of MRSA
infections, vancomycin should be considered as part
of the empiric antibiotic regimen.60
If there is concern for toxic shock syndrome with
fluid-refractory shock, clindamycin should be added
for its antitoxin effects. Antibiotics should be administered through the indwelling catheter and alternated
December 2015 • www.ebmedicine.net
Further Circulatory Management
After aggressive fluid management and improvement in circulatory status, maintenance fluids
should be initiated, if needed. If hepatomegaly or
rales develop after the initial fluid boluses, these
may be signs of fluid overload, and inotropic support should be initiated in lieu of additional fluid
resuscitation. A chest x-ray should be considered to
evaluate for pulmonary edema.
In the setting of fluid-refractory shock, inotropes should be initiated. In most cases of cold shock,
which presents with cool extremities, diminished
peripheral pulses, and delayed capillary refill time,
dopamine is the inotrope that is typically initiated.
Dopamine should be titrated to the goal of reversing
the shock state. Epinephrine can be added if there
is still evidence of a resistant shock state. For warm
shock presenting with warm extremities, bounding peripheral pulses, and flash capillary refill time,
norepinephrine is typically started and titrated to
effect.56,57 In the setting of fluid overload, diuretics
are not recommended until shock has resolved.
Resuscitation with blood products may be indicated in patients with anemia or thrombocytopenia.
In the setting of severe sepsis or septic shock, it is
recommended to transfuse packed red blood cells
to keep the hemoglobin level > 10 mg/dL. Similarly, platelets are indicated in the setting of severe
sepsis or septic shock if the patient’s platelet level
is < 10,000/mcL or < 20,000/mcL with evidence of
clinical bleeding.56
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Clinical Pathway For Management Of Fever Or Suspected Infection
In Pediatric Patients With A Central Venous Catheter
Patient with a CVC presents with fever
or concern for infection
Concern for sepsis?
• Obtain blood cultures (at least
2 cultures from the CVC and a
peripheral vein or from 2 different
lumens), CBC with differential, and
CRP (Class II)
• Culture any drainage from catheter
(Class II)
NO
YES
• Manage airway, breathing, and circulation with supplemental
oxygen and isotonic fluid boluses (20 mL/kg over 5-10 min) up
to 60 mL/kg in 1 hour (Class II)
• Obtain blood cultures (at least 2 cultures from the CVC and a
peripheral vein or from 2 different lumens), CBC with differential, CRP, catheter site drainage culture, if indicated (Class II)
• Administer antibiotics within 60 min; consider whether patient
is likely to be neutropenic, and double cover for gram-negative
organisms if so (Class II)
Improvement in vital signs/reversal of
hemodynamic abnormalities?
Is the patient
neutropenic?
YES
YES
NO
• Consider inotropes (Class II)
• Reassess airway and breathing; increase support as needed
• Consider blood products if Hgb < 10 mg/dL or platelets
< 10,000/ mcL (Class II)
• Consider hydrocortisone (Class II)
• Reverse electrolyte abnormalities (Class II)
• Administer antipseudomonal beta-lactam or
carbapenem (Class II)
• Consider urinalysis
and culture
• Consider imaging if
indicated based on
history and physical
examination (Class II)
Admit patient for
continued antibiotics
and close monitoring
(Class II)
NO
History of MRSA or
infection with resistant
organism?
NO
YES
Administer ceftriaxone
(Class II)
Consider discharge home
with follow-up (Class II)
• Administer vancomycin
• Consider clindamycin if
there is concern for toxic
shock
Admit patient to ICU (Class II)
Abbreviations: CBC, complete blood count; CVC, central venous catheter; CRP, C-reactive protein; Hgb, hemoglobin; ICU, intensive care unit; MRSA,
methicillin-resistant Staphylococcus aureus.
Class Of Evidence Definitions
Each action in the clinical pathways section of Pediatric Emergency Medicine Practice receives a score based on the following definitions.
Class I
• Always acceptable, safe
• Definitely useful
• Proven in both efficacy and effectiveness
Level of Evidence:
• One or more large prospective studies
are present (with rare exceptions)
• High-quality meta-analyses
• Study results consistently positive and
compelling
Class II
• Safe, acceptable
• Probably useful
Level of Evidence:
• Generally higher levels of evidence
• Nonrandomized or retrospective studies:
historic, cohort, or case control studies
• Less robust randomized controlled trials
• Results consistently positive
Class III
• May be acceptable
• Possibly useful
• Considered optional or alternative treatments
Level of Evidence:
• Generally lower or intermediate levels of
evidence
• Case series, animal studies, consensus panels
• Occasionally positive results
Indeterminate
• Continuing area of research
• No recommendations until further
research
Level of Evidence:
• Evidence not available
• Higher studies in progress
• Results inconsistent, contradictory
• Results not compelling
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual
needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2015 EB Medicine. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Medicine.
Copyright © 2015 EB Medicine. All rights reserved.
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Additional Therapies
in conjunction with systemic antibiotics in the setting of CA-BSI. Several catheter lock therapies have
been studied and include antibiotic locks, ethanol
locks, hydrochloric acid locks, and urokinase. The
substance is administered into the hub of the catheter and allowed to dwell for a period of time. The
goal of catheter lock therapy is to reduce the incidence of treatment failure when catheter salvage is
attempted by targeting difficult-to-eradicate biofilms
that are attached to the catheter lumen.
The Infectious Diseases Society of America recommends antibiotic lock therapy in conjunction with
systemic antibiotics in the setting of proven CA-BSI
when catheter salvage is being attempted.6 Antibiotic concentrations needed to kill bacteria contained
within a biofilm are 100 to 1000 times greater than
concentrations that are required to kill free-floating
bacteria. Antibiotic lock treatments can achieve this
concentration within the catheter without systemic
dissemination of the antibiotic. Studies have looked
at the efficacy of antibiotic or other lock therapies in
treating CA-BSIs when catheter salvage is attempted. The results have been varied and, therefore,
there is insufficient evidence to strongly recommend
catheter lock therapies in the setting of CA-BSI.6,63
In patients in a persistent shock state despite appropriate fluid resuscitation and initiation of inotropes,
administration of hydrocortisone should be considered. Shock doses range from 2 to 50 mg/kg/day of
hydrocortisone.57 Electrolyte abnormalities should
be corrected. In particular, glucose homeostasis is essential. Hypoglycemia should be diagnosed promptly and treated with a dextrose bolus. Significant
hyperglycemia should be corrected using insulin
therapy in conjunction with glucose infusion with a
goal serum glucose level of < 180 mg/dL. Hypocalcemia should be reversed with intravenous calcium
gluconate. Hypocalcemia can contribute to cardiac
dysfunction and replacement should be considered,
with care taken to avoid hypercalcemia.57
Considerations Following Initial
Management
After the initial resuscitation and stabilization, the
patient’s primary subspecialty team should be contacted, as they may have additional knowledge of
patient-specific information to aid in management.
This is also particularly relevant when the patient
presents to a hospital where he or she does not
receive ongoing care. The primary subspecialty team
may also have additional recommendations. Furthermore, collaboration with the primary care team
is essential to ensure safe and appropriate disposition of the patient. In patients with a CVC with fever
who have a clear source of infection unrelated to the
catheter, treatment should be tailored specifically to
the cause of the fever, although some would administer empiric broad-spectrum antibiotics until blood
cultures are negative.
Catheter Removal
Immediate catheter removal is not necessary while
awaiting culture results. Removal of a long-term
indwelling catheter is recommended in the following
situations of proven CA-BSI: severe sepsis or septic
shock, suppurative thrombophlebitis, endocarditis,
bloodstream infection that continues to produce
positive cultures despite at least 72 hours of antibiotic
therapy to which the organism is susceptible, or infections due to S aureus, P aeruginosa, fungi, or mycobacteria. Catheter removal may also be necessary when
it is infected with other less virulent (but difficult to
eradicate) organisms, once contamination is ruled
out by multiple positive blood cultures. If removed,
the catheter tip should be sent for culture.6 Despite
this recommendation, catheter removal may not be
feasible in all pediatric patients, given the relative difficulty of obtaining alternative access, and this should
be decided on an individual basis.6,61,62
Catheter Lock Therapies
Catheter lock therapies have been proposed for use
December 2015 • www.ebmedicine.net
Special Circumstances
Neutropenic or otherwise immunocompromised
patients deserve particular attention. The possibility of severe illness or clinical deterioration in these
patients is much higher than in other patients with a
CVC who present with fever or suspected infection.
Prompt evaluation and administration of antibiotics
or other necessary resuscitation are essential. As previously stated, subtle physical examination findings
may be misleading, and all findings on examination
should be investigated further. Communication with
the patient’s primary subspecialty team will help
with appropriate transition of care upon discharge
or admission. Consider intensive care unit evaluation and admission if the patient is ill-appearing or
has unstable vital signs. Controversies And Cutting Edge
Procalcitonin And Other Serum Biomarkers
In children with a CVC presenting to the ED with
fever, it is often difficult to distinguish between a viral etiology and bacterial etiology of fever. There has
been significant investigation into the use of serum
biomarkers to predict infection with viral versus
bacterial pathogens, as well as to predict severity of
disease.
Procalcitonin is a serum biomarker that has been
studied as a potentially useful marker to predict
serious bacterial infection in pediatric patients. Procalcitonin levels have been reported to rise within 3
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to 4 hours in response to infection and reach plateau
levels in 8 to 24 hours,64 making its use in the ED
setting of particular interest.65 High concentrations
of serum procalcitonin have been found in cases of
neonatal sepsis and meningitis and in patients presenting with fever without an identifiable source.51,66
In a study comparing procalcitonin versus CRP,
interleukin-6, or interferon alpha for differentiation of viral versus bacterial infection, procalcitonin
was found to predict serious bacterial infection
better than the other serum biomarkers studied.67
A systematic review and meta-analysis of the role
of procalcitonin in diagnosing severe infection in
neutropenic pediatric patients presenting with fever
found that CRP and procalcitonin had comparable
diagnostic accuracy; however, procalcitonin was
a more specific test for identifying bacterial sepsis
when compared to CRP.68
A study by Kasem et al looked at the diagnostic value of procalcitonin in the setting of pediatric
patients with a CVC presenting with fever. The
results of the study demonstrated that the procalcitonin level of patients with positive blood culture
results was significantly higher than in patients with
negative blood culture results. This was true in both
neutropenic and nonneutropenic patients.69
Results of a separate systematic review and
meta-analysis of the value of serum biomarkers
in predicting adverse outcomes in febrile neutropenic pediatric patients suggest that there is some
improved predictive value of procalcitonin versus
CRP in this population. However, there was significant heterogeneity among the results of the various
studies used in the meta-analysis.65 Haeusler et al
Risk Management Pitfalls For Pediatric Patients With A Central Venous
Catheter Presenting With Fever Or Suspected Infection (Continued on page 13)
1. “The patient was well-appearing in triage, so
she didn’t need to be seen immediately.”
All patients with a CVC presenting with fever
should be evaluated upon arrival. In the setting
of a CR-BSI, a patient’s clinical examination
can change precipitously. Patients presenting
with unstable vital signs should be triaged
and evaluated immediately by an emergency
clinician.
4. “We started antibiotic therapy within the first
hour, but didn’t realize that the patient had a
history of a previous infection with a multidrug-resistant organism.”
Timely and appropriate antibiotic therapy has
been shown to improve outcomes in pediatric
sepsis patients. It is important to consider each
patient’s infection history and cover for resistant
organisms if the patient has a history of a
previous drug-resistant infection.
2. “The patient was tachycardic with fever, but
he had a normal blood pressure, so we didn’t
initially provide any fluid resuscitation.”
In pediatric patients, hypotension is not
required for a patient to meet the criteria for
septic shock, and this is often a late finding. A
patient with evidence of hemodynamic changes
without hypotension is considered to be in
compensated shock. Fluid resuscitation should
be initiated promptly with the goal of reversing
hemodynamic abnormalities such as tachycardia
and hypotension, and normalizing urine output,
mental status, and capillary refill time.
5. “The patient had a CVC and presented with
fever, so blood cultures were drawn from 1 of
2 catheter lumens and empiric antibiotics were
started 2 days ago. Even though the patient was
still febrile after 48 hours, the culture results
were negative, so we discontinued antibiotics.”
A single culture from 1 lumen of the CVC has
been shown in several studies to fail to diagnose
bacteremia in some patients. Cultures should
be drawn from the catheter and a peripheral
vein or from all catheter lumens if a peripheral
culture cannot be obtained. In the setting of a
negative initial culture, repeat cultures should
be obtained, and antibiotics should not be
discontinued if clinical suspicion for bacteremia
remains high.
3. “We were having difficulty accessing the patient’s port, and the parents refused a peripheral blood culture, so the patient didn’t receive
antibiotics for almost 2 hours.”
It is recommended that blood cultures be drawn
prior to the patient’s receiving antibiotics.
However, since prompt antibiotic therapy has
been shown to improve outcomes in neutropenic
and critically ill patients, obtaining cultures
should not significantly delay antibiotic therapy.
Copyright © 2015 EB Medicine. All rights reserved.
6. “All patients with evidence of local catheter
site infections should receive systemic antibiotic therapy.”
When there is evidence of local catheter site
infection, topical antibiotics may be sufficient if
blood culture results are negative and there is no
clinical concern for systemic infection.
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Risk Stratification
conducted an updated systematic review and metaanalysis of the predictive value of biomarkers in the
setting of fever and neutropenia in pediatric cancer
patients. This study included an additional 13 studies that were published after the systematic review
and meta-analysis published by Phillips et al. The
results again demonstrated marked heterogeneity,
making clinical conclusions regarding the utility of
using serum biomarkers in the setting of pediatric
neutropenia difficult.70 While procalcitonin appears
to be a more specific marker for severe bacterial infection than CRP or other serum biomarkers, its utility in the initial diagnosis and management of febrile
pediatric patients is still controversial and cannot be
generalized to all patient populations.
There is considerable interest in the development of
clinical risk prediction rules for febrile neutropenic
pediatric patients. The guideline for management
of children with fever and neutropenia suggests
that each institution should adopt a validated risk
stratification strategy that can be incorporated into
clinical practice.50 However, there are several lowrisk stratification schemas that have been developed
and validated in different populations, making the
uniform use of a single prediction rule unreliable.
A study by West et al identified a temperature of
≥ 39.5°C and a capillary refill time of > 3 seconds
to be associated with the need for critical therapies
(defined as fluid resuscitation beyond 60 mL/kg,
mechanical ventilation, or use of vasoactive medications).63 A systematic review and meta-analysis of
Risk Management Pitfalls For Pediatric Patients With A Central Venous
Catheter Presenting With Fever Or Suspected Infection (Continued from page 12)
9. “An oncology patient with a port presented
with a reported history of fever. We obtained a
blood culture and CBC with differential and determined that the patient was not neutropenic.
We gave him a dose of ceftriaxone and told him
to follow up with his oncologist as needed.”
Well-appearing, nonneutropenic patients with a
CVC may not require admission to the hospital
when presenting with fever. However, proper
follow-up is essential. It is necessary to be in
communication with the patient’s primary care
service (ie, oncology) and ensure that there
is timely follow-up of the cultures drawn.
Furthermore, it should be confirmed that the
patient will be able to return to the hospital
in the event of a positive culture or clinical
deterioration.
7. “The patient has a CVC and is febrile. He is
also complaining of abdominal discomfort.
We drew blood cultures and started antibiotics
prior to admitting him to the general pediatric
service.”
The presence of a CVC does not mean that
the source of the patient’s fever is always the
catheter. In this case, a thorough examination
would have revealed right lower quadrant
tenderness and guarding, and prompted further
evaluation for intra-abdominal pathology.
8. “The patient remained hypotensive after receiving a total of 60 mL/kg of normal saline in
the first hour in addition to antibiotics. Dopamine was initiated; however, we had to titrate
up on the dose due to persistent hypotension.”
In patients with fluid refractory shock after
appropriate resuscitation, inotropes should
be started. If shock persists after the initiation
of inotropic support with the appropriate
escalation to additional inotropes as needed,
hydrocortisone should be considered.
Additional considerations include correcting
electrolyte abnormalities and administering
blood products if anemia or thrombocytopenia
are present.
December 2015 • www.ebmedicine.net
10. “The patient’s blood culture grew coagulasenegative staphylococci at 20 hours, and he was
called back into the ED. He is well-appearing
now, so we did not start antibiotics.”
Coagulase-negative Staphylococcus is a
common skin micro-organism that is often a
contaminant in blood cultures. However, it
can also be pathogenic in these patients, and
it cannot be determined to be a contaminant if
only 1 blood culture is drawn and found to be
positive. Treatment should be continued until
an additional blood culture can be drawn and
determined to be negative.
13
Mobile app access: www.ebmedicine.net/app
the performance of risk prediction rules in children
and young people with febrile neutropenia examined 8 different clinical decision rules. Only 2 studies
in the systematic review included the presence of a
CVC as part of the clinical decision rule. Of these 2
studies, only the “Ammann“ rule was included in
the meta-analysis portion of the study. The pooled
data used in the study to examine this prediction
rule showed high sensitivity to predict patients at
low risk of serious bacterial infection (98%), but
there was a low specificity of 13%.71
While individual institutions may have adopted
an established clinical prediction rule or may have
a protocol for stratifying high-risk versus low-risk
febrile neutropenic oncology patients, it is important
to keep in mind that the presence of a CVC may not
be included in the risk stratification. Furthermore,
while many studies have presented evidence of factors that may influence the risk of severe illness, this
cannot replace individual clinical judgment.
cases of bacteremia were identified in the study. In
all cases of bacteremia, patients received empiric
antibiotics. Ninety percent of these patients were
discharged home from the ED or clinic after receiving antibiotics, and 10% were admitted. All the
patients who were discharged home were successfully called back when cultures resulted positive.
There were no adverse outcomes reported in the discharged group.18 Another retrospective study looked
at 138 nonneutropenic oncology patients with CVCs
presenting to the ED or outpatient clinic with fever,
or who were evaluated in the day-hospital while admitted for chemotherapy.72 A total of 392 episodes of
fever in 138 nonneutropenic subjects were reviewed.
Only 2.5% of patients received empiric antibiotic
therapy. Of the 24 reported episodes of bacteremia in
the study, only 10 cases were admitted from the ED
due to ill appearance or complication with the line.
Of the remaining patients, 7 were sent home without
receiving empiric antibiotics and were later called
back to the ED for a positive culture, 5 cases grew
out during the day-hospital admission for chemotherapy, and 2 were considered contaminated and
the patients were not treated. None of the patients
discharged home and called back for a positive
culture had a reported adverse outcome.72 These
studies suggest that it is possible that some nonneutropenic oncology patients with a CVC presenting
with fever may be discharged with close follow-up.
However, these studies are insufficiently powered to
make definitive conclusions, and institutional protocols should be established to guide the emergency
clinician.
Neutropenic oncology patients will require
admission and continued empiric antibiotic therapy
and monitoring, as they have a higher risk for
clinical deterioration due to sepsis. Other patient
populations may require hospitalization based on
their comorbidities or underlying medical conditions, which make them more susceptible to severe
infection. Pediatric patients with intestinal failure,
for example, can be considered relatively immunocompromised due to chronic malnutrition. They also
have alterations in the integrity of the gastrointestinal tract, making them more susceptible to infection. The standard of care is often to admit these
patients to the hospital while awaiting blood culture
results.73 Similarly, patients receiving hemodialysis
because of end-stage renal disease are also relatively
immunocompromised and are at increased risk for
serious bacterial infection and other complications.
Patients with severe sepsis or unstable vital
signs, or patients who require aggressive fluid resuscitation or other interventions should be admitted
to the intensive care unit for critical care therapy
and closer monitoring.18 For additional information
on the management of septic shock, see the April
2015 Pediatric Emergency Medicine Practice issue titled
Disposition
Most pediatric patients with a CVC presenting with
fever will require admission for continued antibiotic therapy while awaiting blood culture results.
In some cases, well-appearing oncology patients
may be discharged home from the ED if timely and
appropriate follow-up can be ensured, and if the
patient is not neutropenic. A retrospective study by
Kelly et al looked at the incidence of bacteremia in
167 febrile nonneutropenic oncology patients seen
in the ED or outpatient clinic.18 Out of 459 visits, 29
Time- And Cost-Effective
Strategies
• Patients with a CVC presenting with fever
should be evaluated promptly, and antibiotics and other resuscitative measures should be
administered within the first hour.
• The routine use of imaging is not indicated in
most patients with a CVC presenting with fever.
Imaging should be ordered selectively based on
history and physical examination.
• Well-appearing, nonneutropenic oncology
patients with a CVC may not require admission
when they present with fever if appropriate
follow-up can be ensured.
• Developing protocols to standardize the triage
and immediate evaluation of these patients may
save both time and money, and may improve the
quality of care delivered.
• Early consultation with subspecialty services
may improve the time to definitive treatment
and disposition.
Copyright © 2015 EB Medicine. All rights reserved.
14
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“Septic Shock: Recognizing And Managing This
Life-Threatening Condition In Pediatric Patients,”
available at: www.ebmedicine.net/pediatricsepsis.
cent MRSA line infection, you started her on meropenem
and vancomycin, and admitted her to the pediatric floor
for further management.
Summary
References
In pediatric patients with a CVC presenting with
fever, it is often difficult to distinguish between
catheter-associated infections and fever unrelated
to the catheter. A thorough history and physical
examination is essential to uncover any potential
sources of fever. Empiric broad-spectrum antibiotic
therapy should be administered after blood cultures
are obtained. It is important to consider individual
patient-related factors such as any underlying disease
process and any history of previous microbiologically
proven infections when choosing appropriate empiric
antibiotic therapy. In patients presenting with signs
of sepsis or patients who are otherwise unstable,
early resuscitation with the goal of prompt reversal
of hemodynamic abnormalities has been shown to
improve outcomes. Catheter removal is typically not
necessary in the immediate setting and should be
decided on an individual basis. Consultation with the
patient’s primary care subspecialty service is important for current and subsequent management.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are
equally robust. The findings of a large, prospective,
randomized, and blinded trial should carry more
weight than a case report.
To help the reader judge the strength of each
reference, pertinent information about the study, such
as the type of study and the number of patients in the
study will be included in bold type following the references, where available. The most informative references cited in this paper, as determined by the author,
will be noted by an asterisk (*) next to the number of
the reference.
1.
Fletcher M, Hodgkiss H, Zhang S, et al. Prompt administration of antibiotics is associated with improved outcomes
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653 patients)
2.
Jobson M, Sandrof M, Valeriote T, et al Decreasing time to
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3.
Pinon M, Bezzio S, Tovo PA, et al. A prospective 7-year
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5.
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Case Conclusions
Upon initial evaluation, the 8-year-old patient with acute
lymphoblastic leukemia was ill-appearing but nontoxic.
Physical examination revealed evidence of oral mucositis. The remainder of the examination was unremarkable. A blood culture was obtained from his port
as well as a CBC with differential and a CRP. Given
the increased risk of gram-positive organisms in the
presence of mucositis, he was empirically started on cefepime and vancomycin per institutional protocol. The
results of the CBC demonstrated an absolute neutrophil
count of 10 cells/mcL, hemoglobin of 6.4 mg/dL, and a
platelet count of 100,000/mcL. The patient's CRP level
was 2.5 mg/L. You administered a total of 40 mL/kg of
normal saline for tachycardia and transfused 10 mL/kg
of packed red blood cells. Given the patient’s history of
cough prior to presentation, a chest radiograph was obtained, but showed no evidence of acute infiltrate. After
initial resuscitation and antipyretics, the patient’s fever
resolved, and his vital signs improved. Subsequent
evaluation revealed no change in his clinical status,
and you admitted him to the general oncology unit for
continued antibiotic therapy.
Upon evaluation, the 4-year-old patient with gastroschisis appeared clinically dehydrated. You administered 2
20-mL/kg normal saline boluses. You ordered a CBC, and
the results were within normal range for her age. You also
ordered a CRP, which was 1.5 mg/L. You obtained a blood
culture from both lumens of her Broviac® line. Given her
history of multiple resistant organisms and history of reDecember 2015 • www.ebmedicine.net
6.* Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular
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Eggimann P. Diagnosis of intravascular catheter infection.
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Flynn PM. Diagnosis and management of central venous
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10. Fratino G, Molinari AC, Parodi S, et al. Central venous
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11. Bourgeois FC, Lamagna P, Chiang VW. Peripherally inserted
15
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central catheters. Pediatr Emerg Care. 2011;27(6):556-561.
(Review)
29. Robinson JL, Casey LM, Huynh HQ, et al. Prospective cohort
study of the outcome of and risk factors for intravascular
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12. Dyer BJ, Weiman MG, Ludwig S. Central venous catheters in
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30. Marra AR, Opilla M, Edmond MB, et al. Epidemiology of
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31. Sutter D, Stagliano D, Braun L, et al. Polymicrobial bloodstream infection in pediatric patients: risk factors, microbiology, and antimicrobial management. Pediatr Infect Dis J.
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32. Mohammed A, Grant FK, Zhao VM, et al. Characterization
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Cancer. 2012;59(2):410-414. (Prospective study; 178 patients)
33. Silverstein DM, Moylan K. Cause and outcome of central venous catheter infections in paediatric haemodialysis patients.
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17. Adler A, Yaniv I, Steinberg R, et al. Infectious complications
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34. Paglialonga F, Esposito S, Edefonti A, et al. Catheter-related
infections in children treated with hemodialysis. Pediatr
Nephrol. 2004;19(12):1324-1333. (Review)
18. Kelly MJ, Vivier PM, Panken TM, et al. Bacteremia in febrile
nonneutropenic pediatric oncology patients. Pediatr Blood
Cancer. 2010;54(1):83-87. (Retrospective cohort study; 167
patients)
35. Stefanidis CJ. Prevention of catheter-related bacteremia in
children on hemodialysis: time for action. Pediatr Nephrol.
2009;24(11):2087-2095. (Editorial commentary)
19. Janum S, Zingg W, Classen V, et al. Bench-to-bedside review:
Challenges of diagnosis, care and prevention of central
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36. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for
the prevention of intravascular catheter-related infections.
Am J Infect Control. 2011;39(4 Suppl 1):S1-S34. (Practice
guidelines)
20.* Cecinati V, Brescia L, Tagliaferri L, et al. Catheter-related infections in pediatric patients with cancer. Eur J Clin Microbiol
Infect Dis. 2012;31(11):2869-2877. (Review)
37. Bateman SL, Seed PC. Procession to pediatric bacteremia and
sepsis: covert operations and failures in diplomacy. Pediatrics. 2010;126(1):137-150. (Review)
21. Goutail-Flaud MF, Sfez M, Berg A, et al. Central venous
catheter-related complications in newborns and infants: a
587-case survey. J Pediatr Surg. 1991;26(6):645-650. (Retrospective review; 587 patients)
38. Shah SS, Smith MJ, Zaoutis TE. Device-related infections in
children. Pediatr Clin North Am. 2005;52(4):1189-1208. (Review)
22. Randolph AG, Brun-Buisson C, Goldmann D. Identification of central venous catheter-related infections in infants
and children. Pediatr Crit Care Med. 2005;6(Suppl 3):S19-S24.
(Review)
39.* Goldstein B, Giroir B, Randolph A. International pediatric
sepsis consensus conference: definitions for sepsis and organ
dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6(1):2-8.
(Consensus statement)
23. Yeung CY, Lee HC, Huang FY, et al. Sepsis during total
parenteral nutrition: exploration of risk factors and determination of the effectiveness of peripherally inserted central
venous catheters. Pediatr Infect Dis J. 1998;17(2):135-142.
(Prospective study; 378 patients)
40. Band RA, Gaieski DF, Hylton JH, et al. Arriving by emergency medical services improves time to treatment endpoints for
patients with severe sepsis or septic shock. Acad Emerg Med.
2011;18(9):934-940. (Prospective study; 963 patients)
41. Seymour CW, Cooke CR, Heckbert SR, et al. Prehospital
intravenous access and fluid resuscitation in severe sepsis:
an observational cohort study. Crit Care. 2014;18(5):533. (Prospective observational study; 45,394 patients)
24. Ruebner R, Keren R, Coffin S, et al. Complications of central
venous catheters used for the treatment of acute hematogenous osteomyelitis. Pediatrics. 2006;117(4):1210-1215. (Retrospective cohort study; 80 patients)
42. White L, Ybarra M. Neutropenic fever. Emerg Med Clin North
Am. 2014;32(3):549-561. (Review)
25. Tarantino MD, Lail A, Donfield SM, et al. Surveillance of
infectious complications associated with central venous
access devices in children with haemophilia. Haemophilia.
2003;9(5):588-592. (Prospective study; 59 patients)
43. Perrone J, Hollander JE, Datner EM. Emergency department
evaluation of patients with fever and chemotherapy-induced
neutropenia. J Emerg Med. 2004;27(2):115-119. (Retrospective
chart review; 52 patients)
26. Wagner M, Bonhoeffer J, Erb TO, et al. Prospective study
on central venous line associated bloodstream infections.
Arch Dis Child. 2011;96(9):827-831. (Prospective study; 152
patients)
44. Ammann RA, Hirt A, Luthy AR, et al. Predicting bacteremia
in children with fever and chemotherapy-induced neutropenia. Pediatr Infect Dis J. 2004;23(1):61-67. (Retrospective
cohort study; 13 patients)
27. Sumida W, Watanabe Y, Takasu H. Strategies for catheterrelated blood stream infection based on medical course in
children receiving parenteral nutrition. Pediatr Surg Int.
2012;28(1):21-25. (Prospective study; 9 patients)
45. Lucas KG, Brown AE, Armstrong D, et al. The identification
of febrile, neutropenic children with neoplastic disease at
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28. Drews BB, Sanghavi R, Siegel JD, et al. Characteristics of
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101 patients)
Copyright © 2015 EB Medicine. All rights reserved.
46. Richardson MW, Grewal SS, Visintainer PF. Emesis predicts
bacteremia in immunocompromised children with central
venous catheters and fever. Cancer. 2009;115(14):3335-3340.
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62. Leonidou L, Gogos CA. Catheter-related bloodstream infections: catheter management according to pathogen. Int J
Antimicrob Agents. 2010;36(Suppl 2):S26-S32. (Review)
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47. Handrup MM, Moller JK, Rutkjaer C, et al. Importance of
blood cultures from peripheral veins in pediatric patients
with cancer and a central venous line. Pediatr Blood Cancer.
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63. West DC, Marcin JP, Mawis R, et al. Children with cancer,
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48. Scheinemann K, Ethier MC, Dupuis LL, et al. Utility of
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64. Secmeer G, Devrim I, Kara A, et al. Role of procalcitonin and
CRP in differentiating a stable from a deteriorating clinical
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49.* Lehrnbecher T, Phillips R, Alexander S, et al. Guideline
for the management of fever and neutropenia in children
with cancer and/or undergoing hematopoietic stem-cell
transplantation. J Clin Oncol. 2012;30(35):4427-4438. (Practice
guidelines)
65. Phillips RS, Wade R, Lehrnbecher T, et al. Systematic review
and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in
children and young people with cancer. BMC Med. 2012;10:6.
(Systematic review and meta-analysis; 25 studies)
50. Isaacman DJ, Karasic RB, Reynolds EA, et al. Effect of
number of blood cultures and volume of blood on detection of bacteremia in children. J Pediatr. 1996;128(2):190-195.
(Prospective study; 300 patients)
66. Pierce R, Bigham MT, Giuliano JS Jr. Use of procalcitonin for
the prediction and treatment of acute bacterial infection in
children. Curr Opin Pediatr. 2014;26(3):292-298. (Review)
51. Andreola B, Bressan S, Callegaro S, et al. Procalcitonin and
C-reactive protein as diagnostic markers of severe bacterial
infections in febrile infants and children in the emergency
department. Pediatr Infect Dis J. 2007;26(8):672-677. (Prospective study; 408 children)
67. Gendrel D, Raymond J, Coste J, et al. Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferonalpha for differentiation of bacterial vs. viral infections.
Pediatr Infect Dis J. 1999;18(10):875-881. (Prospective study;
700 patients)
52. Pulliam PN, Attia MW, Cronan KM. C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics. 2001;108(6):1275127 (Prospective study; 77 patients)
68. Lin SG, Hou TY, Huang DH, et al. Role of procalcitonin in
the diagnosis of severe infection in pediatric patients with fever and neutropenia—a systemic review and meta-analysis.
Pediatr Infect Dis J. 2012;31(10):e182-e188. (Systematic review
and meta-analysis; 18 studies)
53. Sanders S, Barnett A, Correa-Velez I, et al. Systematic review
of the diagnostic accuracy of C-reactive protein to detect
bacterial infection in nonhospitalized infants and children
with fever. J Pediatr. 2008;153(4):570-574. (Systematic review;
10 studies)
69. Kasem AJ, Bulloch B, Henry M, et al. Procalcitonin as a
marker of bacteremia in children with fever and a central
venous catheter presenting to the emergency department.
Pediatr Emerg Care. 2012;28(10):1017-1021. (Prospective
study; 62 patients)
54. Shachor-Meyouhas Y, Sprecher H, Moscoviz D, et al.
Molecular-based diagnosis of bacteremia in the setting of
fever with or without neutropenia in pediatric hematologyoncology patients. J Pediatr Hematol Oncol. 2013;35(7):500503. (Prospective study; 70 patients)
70. Haeusler GM, Carlesse F, Phillips RS. An updated systematic
review and meta-analysis of the predictive value of serum
biomarkers in the assessment of fever during neutropenia
in children with cancer. Pediatr Infect Dis J. 2013;32(10):e390e396. (Systematic review and meta-analysis; 37 studies)
55. Picardi M, Pagliuca S, Chiurazzi F, et al. Early ultrasonographic finding of septic thrombophlebitis is the main indicator of central venous catheter removal to reduce infectionrelated mortality in neutropenic patients with bloodstream
infection. Ann Oncol. 2012;23(8):2122-2128. (Prospective
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71. Phillips RS, Lehrnbecher T, Alexander S, et al. Updated systematic review and meta-analysis of the performance of risk
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and meta-analysis; 9 articles)
56.* Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis
Campaign: international guidelines for management of
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2013;39(2):165-228. (Clinical practice guidelines)
72. Bartholomew F, Aftandilian C, Andrews J, et al. Evaluation of
febrile, nonneutropenic pediatric oncology patients with central
venous catheters who are not given empiric antibiotics. J Pediatr. 2015;166(1):157-162. (Retrospective review; 138 patients)
57.* Brierley J, Carcillo JA, Choong K, et al. Clinical practice
parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College
of Critical Care Medicine. Crit Care Med. 2009;37(2):666-688.
(Clinical practice guidelines)
73. Chang MI, Carlson SJ, Nandivada P, et al. Challenging the
48-hour rule-out for central line-associated bloodstream
infections in the pediatric intestinal failure population: a
retrospective pilot study. JPEN J Parenter Enteral Nutr. 2015.
Jan 7. [Epub ahead of print] (Retrospective cohort study; 16
patients)
58. Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics. 2003;112(4):793799. (Retrospective cohort study; 91 patients)
59. Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction
duration in pediatric sepsis. Crit Care Med. 2014;42(11):24092417. (Retrospective observational study; 130 patients)
60. Wolf J, Curtis N, Worth LJ, et al. Central line-associated
bloodstream infection in children: an update on treatment.
Pediatr Infect Dis J. 2013;32(8):905-910. (Review)
61. Simon A, Bode U, Beutel K. Diagnosis and treatment of
catheter-related infections in paediatric oncology: an update.
Clin Microbiol Infect. 2006;12(7):606-620. (Review)
December 2015 • www.ebmedicine.net
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CME Questions
3. A 13-year-old girl with a CVC for acute myeloid leukemia presents with fever and altered
mental status. Her vital signs are: temperature,
40°C; heart rate, 180 beats/min; respiratory rate,
40 breaths/min; blood pressure, 90/30 mm Hg;
and pulse oximetry, 88%. She has no evidence
of airway obstruction, but she is lethargic and
poorly responsive to questions. Which of the
following should be the initial management?
a. Application of oxygen via facemask
b. Administration of 1 L normal saline intravenous fluid bolus
c. Administration of dopamine
20 mcg/kg/min
d. Obtaining blood cultures from her CVC and a peripheral vein
e. Empiric administration of cefepime
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4. A 4-year-old boy with acute lymphoblastic
leukemia presents to the ED with a temperature of 38.1°C, cough, and rhinorrhea. He has a
port, and a CBC drawn earlier in the day noted
an absolute neutrophil count of 3500/mm3. He
is well-appearing, with no signs of pneumonia.
Which of the following antibiotic choices is
most appropriate for empiric treatment?
a.Ceftriaxone
b.Cefepime
c.Cefazolin
d.Cephalexin
e.Vancomycin
1. A patient with a central venous line has a fever
to 39°C. Which of the following are considered
risk factors for CA-BSI?
a. Age > 3 years
b. Use of CVC for antibiotic therapy for osteomyelitis
c. Weight > 8 kg
d. Previous stem cell transplantation
e. Absolute neutrophil count of 2000/mm3
2. A 5-year-old boy with a PICC line in his right
arm for treatment for osteomyelitis of his foot
presents to the ED. The previous day, he developed fever, erythema, induration, and tenderness along the tract of the catheterized vein.
What is his most likely diagnosis?
a.Phlebitis
b. Exit site infection
c. Tunnel infection
d. Pocket infection
e. Necrotizing fasciitis
5. A 7-year-old boy with short gut syndrome presents to the ED with a temperature of 39°C. He
has a Hickman® catheter. His heart rate is 170
beats/min, and his blood pressure is 80/40 mm
Hg. He has a history of recurrent CA-BSI, but
his mother is unsure of his recent culture results. Which of the following antibiotic choices
is most appropriate for empiric treatment?
a. Ceftriaxone and clindamycin
b. Clindamycin and cefepime
c. Cefazolin and oxacillin
d. Cefepime and meropenem
e. Vancomycin and meropenem
6. A 3-year-old boy with acute lymphoblastic leukemia presents to the ED with a temperature of
39.2°C. He has a Hickman® catheter, and a CBC
drawn earlier in the day noted an absolute neutrophil count of 150/mm3. He is well-appearing, and the rest of his vital signs are normal.
Which of the following antibiotic choices is
most appropriate for empiric treatment?
a.Ceftriaxone
b.Cefepime
c.Cefazolin
d.Cephalexin
e.Vancomycin
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7. A 12-year-old girl with lymphoma currently
receiving chemotherapy via a CVC was seen in
the ED 2 days ago for fever. The patient’s blood
culture grew coagulase-negative staphylococci
at 36 hours and she was called back to the ED.
She is well-appearing now, with a temperature of 37.9°C, heart rate of 105 beats/min, and
normal blood pressure. She is not neutropenic.
Management should be:
a. Admission for intravenous vancomycin
b. Admission for intravenous meropenem
c. Admission for intravenous meropenem and oxacillin
d. Discharge to home after administration of intravenous ceftriaxone
e. Repeat blood culture and discharge to home without antibiotic therapy
Coming Soon In
Pediatric Emergency Medicine Practice
Diagnostic Emergency
Ultrasound: Assessment
Techniques In The Pediatric
Patient
AUTHORS:
Joshua Guttman, MD, FRCPC
Department of Emergency Medicine, Division
of Emergency Ultrasound, Long Island Jewish
Medical Center, New Hyde Park, NY
Bret P. Nelson, MD, RDMS, FACEP
Director, Emergency Ultrasound, Department
of Emergency Medicine, Icahn School of
Medicine at Mount Sinai, New York, NY
8. An 18-month-old boy with acute lymphoblastic
leukemia presents with a temperature of 39°C.
In addition to a CBC and blood culture, which
of the following tests would be most useful
to predict serious bacterial infection in this
patient?
a. Erythrocyte sedimentation rate
b.CRP
c.Procalcitonin
d.Interleukin-6
e. Interferon alpha
Emergency ultrasound has revolutionized the
prac­tice of emergency medicine. Ultrasound
is an ideal imaging modality in children
due to the need to decrease exposure to
ionizing radiation and because most pedi­
atric patients have a small body habitus.
Emergency ultrasound is applicable across
the field of pediatric emergency medicine,
from trauma to critical care, and increases
the diagnostic ability of pediatric emergency
clinicians beyond the traditional history
and physical examination. Over the last 20
years, the use of ultrasound in the ED has
become a core requirement in emergency
medicine residencies and some pediatric
emergency medicine fellowships. In the
pediatric setting, the growth has been slower,
but there is increasing demand for these
studies. This review focuses on the current
evidence, uses, and techniques for the most
common indications for diagnostic ultrasound,
including:
• Trauma
• Heart
• Lungs
• Abdomen
• Intravascular Volume Assessment
• Testicular Torsion
• Pregnancy
9. Which of the following patients with a CVC
presenting with fever are candidates for outpatient management? Each is well-appearing
with normal vital signs.
a. A 10-year-old with end-stage renal disease dependent on hemodialysis
b. A 5-year-old with short gut syndrome with
a Broviac® catheter, dependent on parenteral nutrition
c. A 3-year-old with intestinal failure with a Hickman® catheter, dependent on parenteral nutrition
d. An 18-year-old with acute lymphoblastic
leukemia who is neutropenic and has a port
e. A 13-year-old with osteosarcoma with an
absolute neutrophil count of 1600/mm3 and a Hickman® catheter
December 2015 • www.ebmedicine.net
19
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Physician CME Information
Date of Original Release: December 1, 2015. Date of most recent review: November 15,
2015. Termination date: December 1, 2018.
SPECIAL
ANNOUNCEMENT
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Goals: Upon completion of this activity, you should be able to: (1) demonstrate medical
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