Pediatrics, Bacteremia and Sepsis

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Pediatrics, Bacteremia and Sepsis

AUTHOR INFORMATION

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Authored by Mary Beth Crawford, MD, Clinical Assistant Professor, Departments of Surgery and Emergency Medicine, Medical College of Ohio, Saint Vincent Mercy Medical Center

Mary Beth Crawford, MD, is a member of the following medical societies: American Academy of Emergency Medicine

Edited by Kirsten Bechtel, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, Yale-New Haven Children's Hospital; Robert Konop, PharmD, Pediatric Clinical Pharmacy Specialist Manager, Clinical Assistant Professor, Department of Clinical Pharmacy, University of Minnesota; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Emergency Medicine and Pediatrics, Toledo Hospital; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and William K Mallon, MD, Program Director, Internship Training, Associate Professor, Department of Emergency Medicine, University of Southern California

Author's Email:	Mary Beth Crawford, MD
Editor's Email:	Kirsten Bechtel, MD

eMedicine Journal, May 22 2001, Volume 2, Number 5

INTRODUCTION

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Background: Although children with bacteremia and sepsis may present with a normal or decreased temperature, patients with these conditions often present with fever. The febrile child represents a diagnostic and therapeutic challenge.

Febrile infants and children younger than 3 years commonly present to the emergency department (ED) for care. The differential diagnosis is broad, ranging from a simple upper respiratory infection (URI) to occult bacteremia and sepsis. Consideration of the child's age, the clinical presentation, the likelihood of a particular diagnosis, the cost of establishing the diagnosis, and the cost of missing the diagnosis are all crucial factors in the evaluation and treatment of these children.

Using low-risk criteria, such as the Rochester Criteria and the Philadelphia Criteria, in infants younger than 3 months may be useful in the clinical setting. Unfortunately, the peer review literature in this arena is full of conflict. Despite a large volume of information available regarding the management of febrile young children, controversy remains. What is essential for the physician to be familiar with current recommended treatment guidelines regarding the febrile young child, and then to apply these guidelines to reasonably approach the evaluation and treatment of the febrile child.

Pathophysiology: Fever in infants and toddlers is defined as a rectal temperature greater than 38°C (100.4°F). Neonates may present with hypothermia rather than fever as a manifestation of occult bacterial illness or sepsis. Tympanic membrane temperatures are unreliable and rectal temperatures should be used for decision-making purposes.

A component of the host's response to bacterial invasion is the release of small molecular weight proteins called cytokines. Cytokines are produced and released from polymorphonuclear cells (PMNs) and phagocytes in response to infectious stimuli. Some cytokines can affect the brain's thermoregulatory center and raise the hypothalamic set point. These cytokines can also stimulate the liver to increase the synthesis of acute phase reactants. These processes lead to the development of fever.

· Fever without a source is defined as a fever with no readily identifiable source of infection in the child despite a careful history and physical examination.

· Occult bacteremia is defined as the presence of a fever, no obvious focus of infection, and a positive blood culture in a child.

· Sepsis is defined as bacteremia with evidence of systemic invasive infection. Septic patients typically appear toxic and may exhibit altered mental status. Vital signs may reveal hyperthermia, normothermia, hypothermia, tachycardia, tachypnea, and/or hypotension.

Frequency:

In the US: As many as 15% of febrile patients aged 3-36 months with no obvious source of infection have occult bacterial infections.

Occult bacteremia occurs in 2.5-6% of children aged 3-36 months with a temperature of greater than 39°C (102.2°F). Children immunized against Haemophilus influenzae type B are at a lower risk than those that are not immunized.
In some studies, the degree of temperature elevation has been shown to be associated with the risk of occult bacteremia, meningitis, and serious bacterial infection (SBI). These studies report that risk increases as the temperature rises from 39°C to 41°C. A fully immunized nontoxic-appearing child with no obvious source of infection and a temperature over 41°C has a 9.3% risk of having occult bacteremia, a 0.25% chance of having meningitis, and less than 1% chance of having SBI. The risk in the same child with a temperature of less than 40.5°C is 3.7%, 0.09%, and less than 0.4%, respectively. The risk in the same child with a temperature of 39-39.4°C is 1.6%, 0.04%, and less than 0.02%, respectively.

This risk stratification has been challenged in recent clinical studies, suggesting that those with temperatures between 38.5-41.1°C all have the same risk of SBI. This controversy emphasizes the importance of clinical judgement and observable variables in the evaluation of this age group.

Mortality/Morbidity: The febrile child is at greater risk if he is inadequately immunized, younger than 3 months, immunocompromised, or if he has a toxic appearance.

The mortality rate for sepsis is age-dependent.

Bacteremia in the neonate (younger than 28 d) more often produces focal infections (eg, meningitis, urinary tract infections) than bacteremia in older infants and children. Consequently, the neonatal age group has the highest morbidity and mortality rates.

Sex: Occult urinary tract infections (UTI) occur in 8-9% of females younger than 2 years presenting with a fever without a source. Occult UTIs occur in 3-4% of males younger than 1 year presenting with a fever without a source. UTIs are more common in uncircumcised males.

Age: The risk of serious bacterial infection, bacteremia, and sepsis is higher in neonates than in infants or children. Several factors contribute to this increased risk, including the following:

Escherichia coli, Listeria monocytogenes and Group B streptococci are the most common pathogens causing SBI in this age group.

A second factor is that physical examination findings are less reliable in the neonate.

Finally, the neonate's immune system is not fully developed.

CLINICAL

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History:

Fever documented at home by a reliable caregiver should be considered equivalent to one documented in the ED or office.

Patient response to antipyretics does not differentiate between bacterial and viral pathogens, nor does it aid in identifying children at risk for serious bacterial illnesses.

Impact of environment, activity level, and recent immunizations are important considerations when evaluating the febrile child. For example, overbundling can increase the temperature by 0.8-1.5°F.

A history of prematurity, lack of immunizations, or other immunocompromised states places the child at higher risk.

A history of recent exposures to sick contacts, recent antibiotics, or recurrent illnesses is useful information.

A history of any change in mental status (eg, lethargy, somnolence, decreased level of activity) may indicate a serious bacterial illness.

A history of an immunocompromised state (eg, chronic steroid use, sickle cell disease, leukemia) is crucial because these patients are not only at higher risk for serious bacterial illness but also are predisposed to different pathogens. For example, patients with sickle cell disease are prone to invasive Salmonella infections.

Physical:

Vital signs should be carefully reviewed; documentation should be accurate and complete. Vital signs should include a rectal temperature, heart rate, respiratory rate, pulse oximetry readings, and blood pressure.

If tachycardia is disproportionate to the degree of fever, consider dehydration, sepsis, and cardiac abnormalities as potential etiologies.

Tachypnea out of proportion to the degree of fever may suggest the early stages of bronchiolitis, pneumonia, or laryngotracheitis.

Hypothermia in the neonate or immunocompromised patient may be the only diagnostic clue to a SBI.

In general, young infants (younger than 3 mo) with serious bacterial illness present with fever and subtle signs, such as irritability or lethargy. Older children often present with specific clinical signs.

Signs of toxicity and sepsis in most infants and children include lethargy, hypotension (easily identified by delayed capillary refill), hypoventilation, hyperventilation, or cyanosis.

When evaluating infants, observational variables can be used as a clinical guide.

Quality of cry

Reaction to parental stimuli

Level of arousal

Color

Hydration status

Response to social overtures

In the older infant and child look for focal findings. These patients often present with the following:

Nuchal rigidity, a positive Kernig sign (pain with passive knee extension with hip flexion)

A positive Brudzinski sign (spontaneous hip flexion with passive neck flexion)

The integument examination often is overlooked and can sometimes provide diagnostic clues. For example, the presence of petechiae and fever represents a broad differential diagnosis that includes meningococcal sepsis, viral exanthems, and Rocky Mountain spotted fever. Approximately 2-8% of children presenting with fever and petechiae will have a SBI, most commonly caused by Neisseria meningitidis.

Causes:

Historically, the most common pathogens causing occult bacteremia in the fully immunized child include the following:

Streptococcus pneumoniae (approximately 98%).

H influenzae type B (under 2%).

N meningitidis, Salmonella species, and others (under 1%).

The incidence of H influenzae type B is believed to have decreased significantly with the introduction of H influenzae type B vaccine after these data were reported.

In the neonate, E coli, Group B Streptococcus, S pneumoniae, and Listeria monocytogenes are the most common pathogens causing sepsis.

In older infants (>3 mo), S pneumoniae, H influenzae (in the unimmunized child), N meningitidis, Staphylococcus aureus, Group A beta hemolytic streptococci, and gram-negative rods are the most common pathogens causing sepsis.

Risk factors influencing susceptibility to occult bacteremia have not been well defined.

A high suspicion in the most common age group (6-24 mo) combined with a compulsive detail-oriented evaluation is perhaps the most helpful tool.

Bacteremia without an obvious focus of infection is uncommon in those older than 2-3 years.

Older children with a SBI are consistently identified by clinical examination.

The risk for SBI and sepsis in the pediatric age group is inversely related to age.

The newborn is at greatest risk for bacterial sepsis. In the absence of dehydration or high environmental temperature, sepsis is a common cause of fever in the first week of life.

SBI accounts for approximately 50% of neonatal deaths in the first month of life.

Exposure to communicable pathogens and immunosuppression are risk factors for the development of sepsis.

Malignancies, chemotherapy, hyposplenism, and sickle cell disease are examples of immunocompromised states placing the child at increased risk.

DIFFERENTIALS

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Pediatrics, Bacteremia and Sepsis
Pediatrics, Bronchiolitis
Pediatrics, Chicken Pox or Varicella
Pediatrics, Croup or Laryngotracheobronchitis
Pediatrics, Crying Child
Pediatrics, Febrile Seizures
Pediatrics, Fever
Pediatrics, Fifth Disease or Erythema Infectiosum
Pediatrics, Gastroenteritis
Pediatrics, Hand-foot-mouth
Pediatrics, Kawasaki Disease
Pediatrics, Meningitis and Encephalitis
Pediatrics, Otitis Media
Pediatrics, Pharyngitis
Pediatrics, Pneumonia
Pediatrics, Roseola Infantum
Pediatrics, Rotavirus
Pediatrics, Scarlet Fever
Pediatrics, Urinary Tract Infections and Pyelonephritis

WORKUP

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Lab Studies:

A complete blood count (CBC) with differential can be a useful screening test in the evaluation of the febrile child without a source of infection on physical examination. The relative risk of bacteremia has been reported to be 5 times higher if the WBC count is greater than 15,000 x 10³/m (13% vs 2.6%). Despite this, many authors challenge the utility of the CBC in bacteremia algorithms. Overall, the CBC has a low sensitivity for sepsis.

Blood cultures remain the criterion standard for identifying children with occult bacteremia. It has been suggested that the WBC count may be used to identify those children warranting a blood culture.

Children aged 3-36 months are at greater risk for occult bacteremia if they have the following:

Fever greater than 39°C
No obvious source of infection
WBC count 15,000-20,000 x 10³/m or less than 5,000 x 10³/m.

Mechanisms must be in place that allow the clinician and the parent or guardian of the child to be notified of the results of blood cultures.

The rate of false positives varies with technique in the ED and the laboratory.

A urinalysis (UA) and urine culture should be obtained on all toxic infants requiring a septic workup.

The most expedient and reliable methods of obtaining urine for UA and culture are a catheterization and a suprapubic tap.

A UA and urine culture should be obtained on all boys younger than 6 months and all girls younger than 2 years presenting with a fever without an obvious source.

UTIs occur in approximately 7-8% of boy infants younger than 6 months and 7-8% of girl infants younger than 2 years with fever.

Stool culture

Helpful when a history or presence of diarrhea exists.

The most cost effective and useful approach may be to obtain a stool culture only when a clinical suspicion of invasive bacterial gastroenteritis (eg, history of bloody or mucoid stools) or if fecal stain findings include greater than 5 WBCs per high-power field (hpf).

Blood chemistries may be indicated when there are clinical signs of altered mental status, dehydration, or seizures, which may have coexisting hypoglycemia or hyponatremia.

Coagulation studies may be warranted on children presenting with a toxic clinical appearance and the presence of a petechial rash.

The C-reactive protein and erythrocyte sedimentation rate (ESR) have been evaluated for their utility in detecting occult bacteremia; however, low sensitivity and specificity limit their usefulness as a screening or diagnostic tool.

Imaging Studies:

General chest radiographs are useful only when clinical evidence suggests a possible respiratory infection or in the neonate whose respiratory signs and symptoms are difficult to identify. Pulse oximetry values may be a reliable predictor of pulmonary infections and should be obtained on the infant and young child presenting with a fever.

If a child presents with a fever and has tachypnea, cough, abnormal oxygen saturation levels, retractions, accessory muscle use, rales, rhonchi, or wheezing, a chest radiograph is indicated. The presence of occult pneumonia in the absence of any of these clinical indicators occurs in fewer than 3% of cases.

High fever (39.0°C), leukocytosis (WBC >20,000 x 10³/m), and unimmunized with the conjugate pneumococcal vaccine place the infant and child at greater risk for bacterial pneumonia; thus, and a chest x-ray is indicated.

Reports state that the conjugate pneumococcal vaccine reduces clinical pneumonia by 10%, radiographic pneumonia by >30%, and pneumonia with consolidation by >70%.

The evaluation of a low-risk infant or child with a fever and no clinical signs or symptoms of pneumonia who has received the pneumococcal vaccine may not warrant an x-ray.

Procedures:

A lumbar puncture is indicated in any child in whom the diagnosis of sepsis or meningitis is being considered. It should be considered in any febrile child presenting with seizure, signs of toxicity, or mental status changes.

TREATMENT

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