Occult Bacteremia

Patients with occult bacteremia do not have clinical evidence other than fever (a systemic response to infection). First described in the 1960s in young febrile children with unsuspected pneumococcal infection, bacteremia is defined as the presence of bacteria in the bloodstream of a febrile child who was previously healthy; the child does not clinically appear to be ill and has no apparent focus of infection.

Occult bacteremia has been defined as bacteremia not associated with clinical evidence of sepsis (shock or purpura) or toxic appearance, underlying significant chronic medical conditions, or clear foci of infection (other than acute otitis media) upon examination in a patient who is discharged and sent home after an outpatient evaluation

Often, the only manifestation of occult bacteremia is fever or a minor infection (eg, otitis media, upper respiratory tract infection). Therefore, in a busy clinic or emergency department, infants and young children with occult bacteremia are difficult to distinguish from others in the waiting-room.

Much of the pathophysiology of occult bacteremia is not fully understood. The presumed mechanism begins with bacterial colonization of the respiratory passages or other mucosal surface; bacteria may egress into the bloodstream of some children because of host-specific and organism-specific factors. Once viable bacteria have gained access to the bloodstream, they may be spontaneously cleared, they may establish a focal infection, or the infection may progress to septicemia; the possible sequelae of septicemia include shock, disseminated intravascular coagulation, multiple organ failure, and death.

A child's immune system helps determine which bacteria gain initial access to the bloodstream, whether bacteremia spontaneously resolves or progresses to serious bacterial illness, and whether cytokines are produced to mount a fever response. The risk of life-threatening bacterial disease is greatest in young infants when their immune system is least mature; they have poor immunoglobulin G (IgG) antibody response to encapsulated bacteria and decreased opsonin activity, macrophage function, and neutrophil activity.

Clearly, some children are more susceptible to bacterial infection, which may initially be uncomplicated bacteremia but could rapidly lead to more serious complications. Immunosuppression due to neoplastic disease or its treatment or defects in antibody responses or neutrophil responses predispose certain children to invasive infection. Bacteremia should be considered, with a low threshold for evaluation and treatment, in patients with impaired immunity or invasive medical devices such as indwelling central venous lines.

Temperature, pulse, respiratory rate, and blood pressure can be very useful in raising clinical suspicion for sepsis or pneumonia and for establishing the risk for occult bacteremia. Studies have also suggested that pulse oximetry should be used routinely as a fifth vital sign. In younger infants, poor perfusion as judged by a capillary-refill time of less than 2 seconds is a more sensitive measure of cardiovascular status than pulse or blood pressure in the early phase of sepsis.

In studies of occult bacteremia, children were not excluded based on specific vital sign parameters; in very young infants, the presence of a serious bacterial infection may not significantly correlate with differences in pulse, respiratory rate, or blood pressure. However, tachycardia, tachypnea, or hypotension in a febrile or hypothermic infant are signs of sepsis and warrant a complete evaluation.

Causes: Causes of occult bacteremia vary depending on the age of the infant or child. Very young infants most commonly acquire infections from the mother during childbirth. As a patient's age increases, a gradual shift occurs toward community-acquired infections.

Occult bacteremia due to S. pneumoniae, H. influenzae tybe B, N. meningitidis and Salmonella spp occures in approximatly 4% of relatively well appearing children S. pneumoniae account for 85% of cases of occult bacteremia, with H. influenzae tybe B, N. meningitidis and Salmonella spp accounting for the remaining postive cultures

The incidence of H. influenza type B infections of all types has decreased dramatically in the regions where the conjugate H. influenza type B vaccine is administered to infants

Older infants and children are at risk for bacteremia due to colonization of the nasopharynx or community-acquired organisms. Hib conjugate vaccine has decreased the prevalence of invasive Hib disease by 90% or more in industrialized countries. With the disappearance of Hib as a cause of occult bacteremia in children, the relative frequency of S Pneumoniae increased in some medical centers to more than 90%. Since the introduction and widespread use of the pneumococcal vaccines, the rate of vaccine-specific strains has dropped considerably, leading to significant changes in the patterns of causative organisms in more recent studies.

Risk Factors of Occult bacteremia: 1. Temprature exceeding 39 C 2. total WBC count greater than /µL or an elevated absolute neutrophil count, band count, ESR, CRP 3. approximately 30% of febrile children months of age have no localized signs of infection

Elements of the history that indicate an increased risk for occult bacteremia in infants and children after the neonatal period include the following: Age, (3- 36 months)which determines the cutoff used to define fever Febrile temperature (≤ 3 mo and temperature >38°C [100.4°F], 3-36 mo and temperature ≥ °C [ °F]) Current antibiotic use Previous hospitalizations Chronic or underlying illness Immunodeficiency (eg, hypogammaglobulinemia, sickle cell anemia, human immunodeficiency virus [HIV], malnutrition, asplenia)

C-reactive protein (CRP) is an acute phase reactant released by the liver following inflammation or tissue damage. Observational studies that have evaluated CRP as a screening tool for occult bacterial infection report a wide range of sensitivity and specificity that vary by cutoff levels used to identify infants and children with serious bacterial infection (SBI). In addition, CRP concentrations generally do not increase until 12 hours after the onset of fever and can rise in both viral and bacterial infections.

- Without therapy occult Bacteremia may resolve spontaneously without sequelae, may persist, or may lead to localized infection, such as meningitis, pneumonia, cellulitis, or septic arthritis - The pattern of sequelae may be related to both host factors & the offending organism - In some children the occcult bacteremia may represent the early signs of serious localized infection rather than transient disease state

Empiric antibiotics: How well do they work? The first step in the treatment of children with occult bacteremia is to use a combination of age, temperature, and screening laboratory test results to determine the risk for serious bacterial infection or occult bacteremia. Low-risk children are generally monitored as outpatients. Children who do not fit low-risk criteria are treated with empiric antibiotics either as inpatients or as outpatients.

Numerous studies have compared the effectiveness of oral antibiotics and parenteral antibiotics in reducing complications of occult bacteremia. Many of these studies were conducted before widespread use of the conjugate Hib vaccine. Parenteral antibiotics were generally found to be significantly more effective than oral treatment or no treatment in reducing the sequelae of occult bacteremia, most importantly meningitis.

Complication No Antibiotic Therapy, % Oral Antibiotic Therapy, % Intramuscular/Intr avenous Antibiotic Therapy, % Persistent bacteremia New focal infection135 – Meningitis – – 1 Occult Bacteremia - Relationship Between Outpatient Antibiotic Use and Complications

Treatment: Practice Giudelines published in 1993 recommended that infants months of age who have temprature less than 39 C and who don’t appear toxic, can be observed as an outpatients without performing diagnostic tests or administering antimicrobial agents.

for non toxic appearing infants with rectal temperature of 39C or greater 2 options are suggested 1. Obtain a blood culture and give empirical antibiotic (Ceftriaxone 50 mg/ Kg) once dialy 2. Obtain CBC and if WBC > or more /µL, obtain blood C&S and give empirical antibiotic therapy

Third option, not offered in this giudelines is to observe selected infants as an outpatients without antibiotics after blood culture has been obtained, the family should be instructed to return to the clinic within 24 hrs if the fever persist or immediately if the child condition deteriorate

Further Inpatient Care, Hospitalization: Neonates younger than 1 month: Most guidelines recommend hospitalization, with or without antibiotic therapy, for all febrile infants younger than 1 month pending culture results.

Infants aged 1-3 months: Most guidelines recommend hospitalization for infants in this age group who do not meet low-risk criteria (ie, they are ill-appearing, appear toxic, are hypotensive, or were not previously healthy or they have a focal infection, high-risk petechiae, UTI, or WBC count per HPF of 15). Infants who need supportive care such as oxygen and intravenous fluids should also be treated as inpatients, as well as those who cannot be treated as outpatients because of caregiver, transportation, communication, or other logistics. Outpatients whose blood or CSF cultures are positive for known bacterial pathogens should be readmitted for intravenous antibiotic therapy.

Children aged 3-36 months: Infants and young children in this age group should be hospitalized if sepsis is a concern because of toxic appearance, unstable vital signs, or high-risk petechiae upon examination. They may also be admitted if they cannot be treated as outpatients because of caregiver, transportation, communication, or other logistics. Many infants and young children in this age group are initially treated as outpatients. They may need to be admitted if a blood culture is positive for known pathogens, depending on the clinical status of the patient and the specific organism grown

Prognosis: Most episodes of occult bacteremia spontaneously resolve, and serious sequelae are increasingly uncommon. However, serious bacterial infections occur, including pneumonia, septic arthritis, osteomyelitis, cellulitis, meningitis, and sepsis; death may result. Evaluation, treatment, and follow-up of febrile infants and young children at risk for occult bacteremia significantly decrease the risk for serious bacterial infections and sequelae.

Complication: Occult bacteremia results in morbidity and mortality due to focal infections that arise following the initial bloodstream infection. Most episodes of occult bacteremia spontaneously resolve, and serious sequelae are increasingly uncommon. However, serious bacterial infections occur, including pneumonia, septic arthritis, osteomyelitis, cellulitis, meningitis, and sepsis; death may result. Of all focal infections that develop because of pneumococcal bacteremia, pneumococcal meningitis carries the highest risk for significant morbidity and mortality, including a 25-30% risk of neurologic sequelae such as deafness, mental retardation, seizures, and paralysis.

Escherichia coli bacteraemia in a pediatric emergency service ( ) authors reported an increase in relative incidence of E. coli bacteraemia in recent years. E. coli has been the third most frequently isolated bacteria in blood cultures at our emergency service between 1995 and Aim: To analyze trends, clinical, laboratory and microbiological data of E. coli bacteraemia in a level 3 pediatric hospital, in the last 16 years. Conclusions: We did not see an increase of community-acquired E. coli bacteraemia over the last 16 years in our hospital. Infections occurred mainly in the neonatal period and first three months of life and the most frequent diagnosis was acute pyelonephritis. Leukocytosis is not always present, particularly in the neonatal period. A quarter of the E. coli was resistant to ampicillin. The outcome was favorable in most children and one died of sepsis. Acta Med Port. Acta Med Port Dec;24 Suppl 2: Epub 2011 Dec 31.

Occult pneumococcal bacteremia: a review. Occult bacteremia is primarily caused by Streptococcus pneumoniae and has been an intense clinical controversy in pediatric emergency medicine, with passionate opinions rendered from inside and outside the field. Vaccine development and widespread immunization have rapidly affected the changing epidemiology of this disease. There is a growing consensus that the reduction in incidence of occult bacteremia and the significant problem of antibiotic resistance are tipping the balance in favor of no testing and no treatment for well-appearing febrile children between 6 and 36 months of age who are immunized with Haemophilus influenzae B vaccination and PCV-7 (pneumococcal conjugate vaccine). This review of occult pneumococcal bacteremia will not only elaborate on current knowledge and clinical practice, but will also provide historical context to this fascinating phenomenon. Pediatr Emerg Care. Pediatr Emerg Care Jun;26(6):448-54; quiz

Reduced use of occult bacteremia blood screens by emergency medicine physicians using immunization registry for children presenting with fever without a source. OBJECTIVES: This study examined whether utilization of the Florida State Health Online Tracking System (SHOTS) immunization registry to determine Haemophilus influenzae type B and heptavalent pneumococcal conjugate (PCV7) vaccine status impacts the protocolized decision to perform a screening blood draw for occult bacteremia (OB) in young children. METHODS: A convenience sample of children 6 to 24 months of age presenting to the pediatric emergency department with fever of greater than 39°C without a source was enrolled. Physicians were trained to use the SHOTS immunization registry and reviewed the emergency department's fever protocol. A "preregistry" workup plan was documented for each patient based on clinical history, immunization status before accessing SHOTS, and physical examination. A "postregistry" workup plan was then documented based on the SHOTS record. Demographic and registry data were recorded.

RESULTS: Preregistry workup plans indicated OB screening blood draws for 100% (n = 91; 95% confidence interval [CI], ) of patients with unconfirmed immunization status. Of those 91 children, 58% (n = 53; 95% CI, 55-61) were documented in SHOTS as having received their primary conjugate vaccine series at ages 2, 4, and 6 months. Registry access reduced the percentage of screening blood draws from 100% (n = 91) to 42% (n = 38; 95% CI, 37-53; P < 0.001). CONCLUSIONS: The state immunization registry is an adjunctive tool to caregiver recall, which can be used by emergency medicine practitioners to confirm completion of the primary conjugate vaccine series before making the decision to perform blood screens for OB in children aged 6 to 24 months who present with fever without a source. Pediatr Emerg Care Jul;28(7):640-5.