Occult Bacteremia in Children: Risk Assessment, Predicting Outcomes,and Antibiotic Therapy
Author: Steven G. Rothrock, MD, FACEP, Research Director, Depart-ment of Emergency Medicine, Orlando Regional Medical Center & Arnold Palmer’s Hospital for Women and Children, Orlando, FL; Clinical Assistant Professor, Division of Emergency Medicine, University of Florida College of Medicine, Gainesville, FL.
Peer Reviewers: Larry B. Mellick, MD, MS, FAAP, FACEP, Professor and Chair, Department of Emergency Medicine, Director of Pediatric Emergency Medicine, Medical College of Georgia, Augusta, GA.
Michael Gerardi, MD, FAAP, FACEP, Director, Pediatric Emergency Medical Services, Saint Barnabas Medical Center, Livingston, NJ.
Occult bacteremia in children: treacherous, confusing, and controversial. How treacherous? How confusing? Put simply, identifying and treating occult bacteremia (OB) in the pediatric age group is a risk management and risk stratification nightmare. In fact, few life-threatening conditions present such difficultand, sometimes, ambiguoustriage and treatment decisions.
The scenario is a familiar one for seasoned practitioners of emergency medicine. Typically, an infant or young child arrives in the ED with a temperature greater than 39°C, appears to be ill, but no source of minor or major infections is readily identified. The clinical dilemma quickly thickens and the ED physician must arrive at answers to a number of critical questions. What is the likelihood this patient has OB? How extensive should the laboratory evaluation be? What clinical features can help distinguish between "low-risk" and "high-risk" patients? Is empiric antibiotic treatment justified? Will an oral agent suffice? Is hospitalization necessary?
Although definitive guidelines for managing these patients are still a matter for debate, recent studies help point the emergency physician toward outcome-effective assessment and treatment strategies.1-4 For example, whereas Haemophilus influenzae type B once was the most common cause of OB, today the most common etiologic agent causing OB in children who have been immunized against H. influenzae is Streptococcus pneumoniae.5,6 Complicating the development of strict guidelines for antibiotic use is the fact that most recommendations for antimicrobial intervention were made prior to the dramatic decline in H. influenzae disease, which can be extremely invasive and produce such sequelae as meningitis and pneumonia.7,8
Despite the emergence of expert guidelines and recommendations, many issues surrounding this important clinical syndrome remain unanswered. With these uncertainties and gaps in knowledge in mind, this review presents a systematic, evidentiary-based analysis of OB. By emphasizing possible causes, risk factors, and predictive clinical signs, this issue will permit ED practitioners to make informed and logical decisions that will help optimize care in children suspected of having OB.
The Editor
Definitions and Risk Management Issues
OB occurs when a well-appearing child, with no major focus of infection, is bacteremic. The highest age incidence of OB is 6-24 months, although cases occur outside this range.9 The most common organisms implicated in OB include S. pneumoniae and H. influenzae type b, accounting for approximately 99% of all cases. With the recent introduction of the H. influenzae vaccine, however, the incidence of H. influenzae bacteremia has decreased dramatically.1-3,5,6
The incidence of OB has been reported to be as high as 2.8-11.1% in febrile children 3-36 months old.5,10-13 Many prior studies citing a high incidence of bacteremia were simple chart reviews limited by the inclusion of children who were ill-appearing or had serious bacterial infections when their blood cultures were obtained; consequently, they falsely overestimated the incidence of this disorder.5,10-13 Recently, the largest prospective study of OB ever published (including ~ 6700 consecutive febrile children) found that the incidence of OB was 2.8% in well-appearing children 3-36 months old with temperatures of 39°C or higher.5 This single study was larger than all other OB studies combined, had rigorous criteria for patient inclusion (defined age, temperature, and criteria for well-appearance), and thorough follow-up; as a result, it conveys a more accurate estimate of the prevalence of OB. Well-appearing children with upper respiratory infections, otitis media, diarrhea, and wheezing were included in this study and were found to have a similar incidence of OB compared to those with no apparent source of infection.5
Natural History of Occult Bacteremia?
Fortunately, most cases of OB will clear spontaneously. However, a subset of bacteremic children will develop serious infectionsmost importantly meningitis.4 A recently published meta-analysis of OB studies found that parenteral antibiotics administered at the time the blood culture was obtained were effective in decreasing the risk of meningitis in children with H. influenzae OB from 25% to less than 1%.4 Oral antibiotics, however, were found to be ineffective in preventing sequelae from H. influenzae bacteremia.4 Fortunately, the incidence of H. influenzae disease has markedly decreased and is of less concern in fully immunized children.1-3 For cases of OB due to S. pneumoniae, the risk of progression to meningitis fell from 6% to less than 1% when either oral or parenteral antibiotics were administered.4 More recently, this meta-analysis was repeated, excluding studies of ill-appearing children, admitted children, and children who underwent spinal taps (ill-appearing children who underwent a procedure known to seed the CSF) on their initial physician encounter. This repeat meta-analysis found that the risk of S. pneumoniae bacteremia progressing to meningitis was less than 3% and that oral antibiotics were not effective in preventing meningitis.8
Risk Stratification and Predictive Value of Clinical Findings
Several findings may be useful for identifying the presence of OB and its progression to more serious disease. These include:
• The degree of the temperature elevation
• The presence of a minor or major source of infection
Height of the Temperature. While the incidence of OB in well-appearing children (3-36 months of age) with a temperature of 39°C (102.2°F) or higher has been reported at 2.8-11.1%,5,10-13 this number was actually found to be about 2.8% in the largest study of OB.5 In fact, if children with H. influenzae are excluded (i.e., if only children who are fully immunized against H. influenzae are considered), the incidence of bacteremia falls to less than 2.5%.5 The risk of harboring OB rises with the height of a child’s temperature, although even at temperatures of 41°C or higher, most well-appearing children are not bacteremic.6 Moreover, the risk of a child who is fully immunized against H. influenzae developing a serious bacterial infection or meningitis increases as the temperature rises. (See Figure 1.)
It is apparent that even at very high temperatures (41°C [105.8°F] or higher), the vast majority of well-appearing children (well over 90%) are not bacteremic and will not develop a serious bacterial infection.
Because the risk of bacteremia rises with temperatures higher than 39°C (102.2°F), some authors, including a recent expert panel, recommend obtaining a blood culture (and initiating empiric antibiotic therapy) on all patients with a temperature above this level or obtaining a blood culture and initiating treatment only on those with an elevated temperature (above 39°C) and a white blood cell count greater than 15,000 cells/mm3.7 However, this approach has been questioned.14,15
While the height of the temperature has a positive correlation, reliance on this parameter alone will not detect all cases of bacteremia. In fact, bacteremia (due to H. influenzae and S. pneumoniae) still occurs at lower temperatures, with up to 13% of bacteremic children afebrile on presentation to an ED.16 On the other hand, the persistence of a fever after 48 hours of antibiotic therapy is associated with an increased risk of bacteremia and infectious complications.12
The Child’s Age. Prior studies of OB have found that most children who are bacteremic are between the ages of 6 and 18 months.9 (See Figure 2.) Those who are younger than 6 months old retain protective maternal antibodies against common organisms, whereas those older than 18-24 months are more immunocompetent and at lower risk for developing bacteremia. However, the drop-off in the incidence of bacteremia noted by several authors may be misleading since clinicians may not look for bacteremia in children older than 24 months or younger than 3-6 months.
The White Blood Cell Count. The white blood cell (WBC) count has been promoted as a useful tool for evaluation of well-appearing children suspected of having OB. Published guidelines recommend a WBC cut-off of 15,000 cells/mm3 or greater as a trigger for obtaining a blood culture and consideration of empiric antibiotic therapy.7 However, using this cut-off as a trigger for culture and treatment misses up to 35% of bacteremic children.13 Furthermore, the positive predictive value of this cut-off is less than 10% (i.e., < 1 in 10 children with a WBC count of ³ 15,000 cells/mm3 will be bacteremic). While a lower WBC cut-off of 10,000 cells/mm3 would detect 92% of bacteremia cases, the positive predictive value falls to less than 3% (i.e., < 3 in 100 children with a WBC count ³ 10,000 cells/mm3 will be bacteremic).7,13 (See Figure 3.) Finally, the addition of a WBC count to the work-up of every febrile child with a temperature of 39°C (102.2°F) or greater may cause delays in treatment and added expense while contributing little useful information to the evaluation of the well-appearing child.
Other Laboratory Tests. The C-reactive protein and erythrocyte sedimentation rate have been evaluated for detecting OB. A sedimentation rate of greater than 30 mm/h or an elevated C-reactive protein denotes a 10-15% incidence of bacteremia in a febrile child.17,18 Unfortunately, the high rate of false positives and false negatives limits the use of these tests for detecting OB.
Blood CulturesAn Unreliable Gold Standard. Blood cultures are considered the gold standard for identifying children with bacteremia. Unfortunately, several problems exist with this test that diminish its clinical usefulness. The average time for cultures to return as positive varies from 24 to 48 hourstoo late to make initial treatment decisions. Furthermore, more than two-thirds of positive cultures are actually false positives.19,20 One recent study found that 58% of all children with true positive blood cultures were either lost to follow-up, returned to a physician prior to the culture turning positive, or followed up due to a scheduled appointment prior to the culture returning positive.21 In the remainder, the blood cultures prompted an unscheduled return visit.
Recent evidence suggests that increasing volume to 3 mL may increase the sensitivity for cultures detecting bacteremia and shorten the time that it takes for a culture to turn positive.22
The culture technique used is also important. Three common systems include the BACTEC NR660, the BACTEC 9240 (Becton Dickinson Diagnostic Instrument Systems, Sparks, MD) and the BacT/Alert (Organon Teknika Corporation, Durham NC). With these three techniques, culture bottles are monitored for positivity by instruments that detect the CO2 released from the culture broth during organism growth and metabolism using infrared spectroscopy (BACTEC NR 660), fluorescent CO2 sensors (BACTEC 9240), or a colorimetric method (BacT/Alert).23,24 The BACTEC NR 660 permits reading for positive cultures one or two times per day, while the alternate methods allow continuous monitoring of culture bottles.23,24 Thus, laboratories using the BACTEC NR 660 method are significantly slower in reporting positive cultures compared to other methods. A newer blood culture technique (DIFCO ESP) monitors each culture for any increase or decrease in internal atmospheric pressure due to gas production or use.24 This technique has a higher total aerobic culture rate, and a significantly decreased mean turnaround time for positive cultures compared to BacT/Alert.24 Clinicians should be aware of the specific culture technique used in their laboratory and, if necessary, consider advocating an upgrade to one of the newer techniques.
Other problems exist with reliance on blood cultures to make decisions. Most cases of S. pneumoniae OB will spontaneously clear.4 Moreover, blood cultures may not identify all children who eventually develop serious infections or become ill. Additionally, in one recent series, 24% of those without bacteremia who were treated with oral antibiotics required a second physician visit during their illness. In this same series, about 25% developed diarrhea, vomiting, or a rash, and a significant number required hospitalizations due to antibiotic-related side effects.5
Minor Infections: Implications. Debate exists as to whether children with a fever and otitis media, upper respiratory infection, or diarrhea require evaluation for OB. It should be stressed that bacteremia can occur in a substantial number of children with these minor infectious sources. In the large series of 6700 children with acute fever and no major infectious source, 12.8% of children with otitis media were bacteremic, although only one patient developed a serious bacterial infection.5 Others have reported a bacteremia rate for children with otitis media of 3-6%, which is similar to the child with fever and no source.7,25 However, those with focal minor infection (e.g., otitis media, upper respiratory infections) may have lower serum bacterial concentration (< 100 CFU/mL) and thus may be at lower risk for progression to meningitis and other serious bacterial infection.9,26,27 Thus, the rate of serious bacterial infections developing following bacteremia may be lower in these patients than that of a child with fever and no source.5,15
Missing Major Infection. Prior to considering the diagnosis of OB in febrile children with no obvious infectious source, clinicians must consider whether a major focus of infection is present with only minimal clinical signs. Most importantly, clinicians must consider and exclude the diagnosis of meningitis either by history and physical examination or by performing a lumbar puncture. While most children older than 24 months manifest nuchal rigidity and other meningeal signs when they develop meningitis, those who are under the age of 18-24 months and those who have been pretreated with antibiotics may not uniformly manifest meningeal signs or an altered mental status.28 (See Figure 4.) Furthermore, as many as 30% with meningitis may concurrently display signs and symptoms of upper respiratory infections including, but not limited to, otitis media and pharyngitisthus, potentially leading to diagnostic delays.29
Urinary tract infections (UTIs) are another important class of infections that may present with few or no localizing signs and symptoms. In one series of children under age 3, 80% with UTIs manifested irritability; 65%, poor feeding; 40%, vomiting; 30%, diarrhea; and a smaller percentage had a cough or nasal discharge.30 Each of these symptoms occurred with equal frequency in febrile children with and without UTIs and, thus, were useless diagnostically.30 Moreover, nearly 9% of females with fever 39°C or higher, 7.5% of all children with fever and no source, 3.5% with fever and otitis media, and 1.5% with fever and an unequivocal source (e.g., pneumonia) had a UTI.30 Thus, UTIs must be considered and excluded in most children at risk for OB.
Finally, minimal localizing signs and symptoms may occur in infants and children with osteomyelitis, septic arthritis, bacterial diarrhea, pneumonia, and other serious bacterial infections. To exclude these disorders, a thorough evaluation must be performed before determining that no source for a child’s fever is present.
Clinical Support Tools. When the Yale Observation Scale (YOS) was first described by McCarthy and colleagues in 1982, it was found to be useful, although not 100% accurate, in discriminating ill- from non-ill-appearing children.31 This scale allowed clinicians to apply an objective description to their clinical assessment of febrile children. (See Table 1.) Two separate reports have examined the utility of the YOS in detecting bacteremia. In an earlier study of the fever response to acetaminophen, a YOS score of greater than 10 was found to be 68% sensitive and 77% specific in detecting bacteremia.31 A larger prospective study by Teach and associates found that 71% of febrile children with OB had the lowest possible YOS, 6.32 Importantly, this score was only 17% specific for diagnosing OB.32 As the YOS increased to 8 or greater, specificity for diagnosing OB increased to 83%, while sensitivity dropped to 29%.32 (See Figure 5.) Thus, no YOS cut-off had reliable sensitivity or specificity for detecting bacteremia, limiting the utility of this single feature in accurately diagnosing or excluding OB.
Immune Status and Other Risk Factors. Children who are immunocompromised, including those with leukemia or HIV, are more likely to harbor bacteremia than normal children when they develop a fever. A recent study found a 9% prevalence of bacteremia in HIV-positive children who presented to one pediatric ED.33 Organisms responsible for bacteremia were frequently atypical: for example, Streptococcus faecalis, Escherichia coli, Torulopsis glabrata, and non-aureus Staphylococcus species. Importantly, half of all HIV-positive children with positive blood cultures had temperatures below 38°C, although most had central lines and a history of a fever.33
Immunization status is another important consideration in children at risk for bacteremia. Children not immunized against H. influenzae type b run a higher risk of developing serious bacterial infections from this organism, as it is much more invasive and more likely to progress to meningitis compared to S. pneumoniae.4
Important risk factors for invasive S. pneumoniae disease include institutional day care center attendance (36-fold increased risk), family day care center attendance (4.4-fold increase), and frequent otitis media (8.8-fold increase).34 The presence of any of these risk factors should heighten the suspicion that S. pneumoniae OB is present.
The Role of Parents. An important factor that often is not considered in evaluating and managing children with febrile illness is the preference of the parents. In general, parents prefer to forego the short-term definite risk of a painful blood draw, urine catheterization, or antibiotic injection while accepting the long-term possible risk of a serious infection developing.35,36 An informed explanation of the risks and benefits with careful follow-up may be appropriate for parents who wish to avoid a blood culture and empiric antibiotic therapy for OB.
A final factor to be considered is the reliability of parents. Children have the poorest compliance with mandatory follow-up (only 16% in one series) of all types of patients who present to EDs.37 Furthermore, caretakers who are younger than 21 years old, without a car, and who feel that their child is not ill are significantly less likely to comply with mandatory follow-up from the ED.38 One method to ensure follow-up is employment of a visiting nurse. This approach virtually guarantees follow-up and allows for a health care professional to visit the home and evaluate the infant for improvement or progression of their disease at a specified time while also saving money.39
Guidelines for Managing Occult Bacteremia
Two sets of guidelines for managing febrile children with possible OB have recently been published. In 1993, the American College of Emergency Physicians published a Clinical Policy for the Initial Approach to Children Under the Age of 2 Years Presenting with Fever.40 This publication details Rules (actions reflecting principles of good practice in most cases that should be performed on all children with specific complaints) and Guidelines (lists of recommendations that should be considered, but may or may not be performed, depending on the patient, the circumstances, or other factors.) This clinical policy details recommendations for the care of children with abnormalities of major organ systems, specific infections, and specific complaints (e.g., children of different ages who have fever without a source). Deviations from rules are acceptable if a detailed explanation or reason is documented in writing.
For children 1-24 months of age and a fever without a source (with a temperature > 40°C [104°F]), ACEP recommends a thorough head-to-toe examination as a rule.40 Guidelines to consider depending upon the clinical examination include the following: glucose, CBC, urinalysis, urine culture, blood culture, chest radiography, lumbar puncture, external cooling if the temperature is greater than 40.6°C (105°F), antipyretics, antibiotics, and referral for follow-up within 24 hours if not admitted.40 No specific recommendations were made regarding management of children with suspected OB. Importantly, a temperature cut-off for considering blood cultures was listed as 104°F. Moreover, the route and choice of antibiotic was left to the discretion of the treating clinician in children with fever and no source. While ACEP recommendations were published to set a standard of care, they are broad, attempt to cover a wide variety of pediatric infectious disease, and leave considerable leeway for interpretation and implementation. In fact, a computer science method known as decision table analysis used to verify ACEP’s practice guidelines found more than 23,000 possible options available for managing febrile children.41 Furthermore, according to the authors of this abstract, the guidelines were found to be "inconsistent," with too many "contradictions and undecidable points."41
A second expert panel comprised of pediatric emergency physicians, infectious disease specialists, and pediatricians published recommendations primarily for children 0-3 years old.7 The expert panel’s recommendation for children 3-36 months old with a fever without a source are more specific than those devised by ACEP. Non-toxic children (males < 6 months and females < 2 years) with a temperature of 39°C (102.2°F) or higher all should receive a urine culture.7 Blood cultures and empiric antibiotic therapy (parenteral ceftriaxone 50 mg/kg IM or oral amoxicillin 60 mg/kg/d for 3 days) are recommended for all children or only those with WBC counts of 15,000 cells/mm3 or higher.7 While these guidelines are much more specific and useful from the standpoint of giving a standard or a reference of how to evaluate these children, several problems exist. Importantly, WBC cutoffs are either insensitive or nonspecific for detecting bacteremia. Furthermore, these guidelines were written and published based on studies that found a high incidence of H. influenzae bacteremia. H. influenzae is much more invasive than S. pneumoniae, and its dramatic decline in incidence means that most future cases of bacteremia will clear spontaneously.
Moreover, a recent meta-analysis published as an abstract found that the incidence of meningitis following S. pneumoniae bacteremia may be much lower than previously reported (< 3% instead of 5.8%).8 Furthermore, oral antibiotics were not found to be effective in preventing pneumococcal meningitis.8 The widespread use of antibiotics for the prevention of bacteremia complications in all children with temperatures of 39°C or higher may have some negative effects, including: 1) development of partially treated meningitis, making diagnosis more difficult; 2) increased drug resistance; 3) increased delays and costs of ED visits; and 4) side effects requiring a second physician visit in up to 20% (with potential hospital admission)5 in those receiving antibiotics.
Finally, obtaining blood cultures and treating all children with temperatures of 39°C or higher will not ensure that all cases of bacteremia will be detected and treated. Obtaining only one blood culture does not provide the sensitivity or reliability to detect bacteremia consistently. In addition, arbitrary use of 39°C as a temperature cut-off for empiric antibiotic treatment is based on an erroneous assumption that bacteremia does not exist when the temperature is less than 39°C.
Several treatment options for managing children with possible OB exist. The first option is adherence to the expert panel guidelines of obtaining a blood culture and treating all children with a temperature of 39°C or higher and fever without a source. Clinicians should realize that this approach will detect most cases of bacteremia while needlessly treating a large number of children without bacteremia.
A second option for emergency physicians who are extremely comfortable with their ability to assess and manage febrile children is to selectively culture and treat those who are at the highest risk for OB using the following factors: patient age, the height of the temperature, the child’s immune status, the presence or absence of a minor source of infection, parental preference and reliability, and the child’s clinical examination (observation). Blood culture and treatment should be considered in children with temperatures of 40°C or higher or temperatures of 39°C or higher with: 1) YOS score > 6; 2) less than full H. influenzae type b immunization; 3) no minor source for infection; 4) age of 6-24 months; 5) unreliable parents; or 6) parents who desire treatmentif they understand an explanation of the potential risks and benefits of treatment vs. non-treatment. This approach will potentially miss more cases of bacteremia, while only children at highest risk are cultured and treated and fewer non-bacteremic children will be subjected to needless evaluation and antibiotic side effects. Most importantly, all patients should receive a mandatory re-evaluation within 24 hours regardless of which approach is taken.
Evaluation of infants and children who have fever without a source requires understanding the subtle nature and presentations of UTIs and meningitis at this age as well as the multiple factors that place children within this age range at risk for OB. No single approach will identify and treat all children with bacteremia. Use of the expert panel guidelines will detect the most cases of bacteremia while overtreating a large number of children without bacteremia. Adherence to this approach should be considered by all clinicians who do not treat and evaluate febrile children on a routine basis. For those clinicians who are experienced and feel comfortable with their ability to assess febrile children and with their knowledge of risk factors for OB, a more selective approach of careful follow-up and selective culturing and treatment of only those at highest risk for OB is acceptable. This approach will detect fewer cases of OB while curtailing the over-treatment of non-bacteremic children. Regardless of which approach is taken, 24-hour follow-up of at-risk children, as well as an explanation to the parents or caretaker of the risks of a febrile illness potentially progressing to more serious illness, are mandatory. Re-evaluation by a physician may be the best way to ensure that no serious bacterial infection has developed in those at risk for OB.
References
1. Adams WG, Deaver KA, Cochi SL, et al. Decline of childhood Haemophilus influenzae type b (HIB) disease in the HIB vaccine era. JAMA 1993;269:221-226.
2. Broadhurst LE, Erickson RL, Kelley PW. Decreases in invasive Haemophilus influenzae diseases in U.S. Army children, 1984 through 1991. JAMA 1993;269:227-231.
3. Vadheim CM, Greenberg DP, Eriksen E, et al. Eradication of Haemophilus influenzae type b disease in Southern California. Arch Pediatr Adolesc Med 1994;148:51-56.
4. Baraff LJ, Oslund S, Prather M. Effect of antibiotic therapy and etiologic microorganisms on the risk of bacterial menin -gitis in children with occult bacteremia. Pediatrics 1993;92:140143.
5. Fleisher GR, Rosenberg N, Vinci R, et al. Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia. J Pediatr 1994;124:504-512.
6. Harper MB, Fleisher GR. Occult bacteremia in the 3-month-old to 3-year-old age group. Pediatr Ann 1993;22:484-493.
7. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guidelines for management of infants and children 0-36 months of age with fever without source. Pediatrics 1993;92:1-12.
8. Rothrock SG, Green SM, Clark M. Do oral antibiotics prevent meningitis in children with occult pneumococcal bacteremia? A meta-analysis. Acad Emerg Med 1995;2:A.
9. Sinkinson CA, Pichichero ME. Occult bacteremia in children: What are the odds? Emerg Med Rep 1991;12:1-10.
10. Teele DW, Pelton SI, Grant MJA, et al. bacteremia in febrile children under 2 years of age: Results of cultures of 600 consecutive febrile children seen in a walk-in clinic. J Pediatr 1975;87:227-230.
11. Schwartz, RH, Wientzen RL. Occult bacteremia in toxic appearing febrile infants. a prospective clinical study in an office setting. Clin Pediatr 1982;21:1175-1180.
12. Jaffe DM, Tanz RR, Todd-Davis A, et al. Antibiotic administration to treat possible occult bacteremia in febrile children. N Engl J Med 1987;317:1175-1180.
13. Jaffe DM, Fleisher GR. Temperature and total white blood cell count as indicators of bacteremia. Pediatrics 1991;87:670-674.
14. Cox RD, Wagner M, Woolard DJ. Infants and children with fever without source. Ann Emerg Med 1994;23:598-600.
15. Long SS. Antibiotic therapy in febrile children: "Best-laid schemes . . . " J Pediatr 1994;124:585-588.
16. Kline M, Lorin M. Bacteremia in children afebrile at presentation to an emergency department. Pediatr Infect Dis J 1987;6:197-201.
17. Bennish M, Beem MO, Orniste V. C reactive protein and zeta sedimentation ratio as indicators of bacteremia in pediatric patients. J Pediatr 1984;104:729-732.
18. McCarthy PL, Jekel JF, Dolan TF. Comparison of acute-phase reactants in pediatric patients with fever. Pediatrics 1978;62: 716.
19. Lyman JL. Use of blood cultures in the emergency department. Ann Emerg Med 1986;15:308-331.
20. Stair TO, Linheart M. Outpatient blood cultures: Retrospective and prospective audits in one ED. Ann Emerg Med 1984;13:986-987.
21. Joffe M, Avner JR. Follow-up of patients with occult bacteremia in pediatric emergency departments. Pediatr Emerg Care 1992;8:258-261.
22. Karasic RB, Isaacman DJ, Reynolds EA, et al. Effect of number of blood cultures and volume of blood on detection of bacteremia in children. J Pediatr 1996;128:190-195.
23. Morello JA, Leitch C, Nitz, et al. Detection of bacteremia by Difco ESP blood culture system. J Clin Microbiol 1994;32:811-818.
24. Zwadyk P, Pierson CL, Young C. Comparison of Difco ESP and Organon Teknika BacT/Alert continuous monitoring blood culture systems. J Clin Microbiol 1994;32:1273-1279.
25. Schutzman SA, Petrycki S, Fleisher G. Bacteremia with otitis media. Pediatrics 1991;87:48-53.
26. Bell LM, Alpert G, Campos JM, et al. Routine quantitative blood cultures in children with Haemophilus influenzae or Streptococcus pneumoniae bacteremia. Pediatrics 1985;76:901-904.
27. Sullivan TD, LaScolea LJ, Neter E. Relationship between the magnitude of bacteremia in children and the clinical disease. Pediatrics 1982;69:699-702.
28. Kelly-Walsh C. Nelson DB, Smith DS, et al. Clinical predictors of bacterial versus aseptic meningitis in childhood. Ann Emerg Med 1992;21:910-914.
29. Rothrock SG, Green SM. Pediatric bacterial meningitis: Is preliminary antibiotic therapy associated with an altered clinical presentation? Ann Emerg Med 1992;21:146-154.
30. Hoberman A, Chao HP, Keller DM, et al. Prevalence of urinary tract infection in febrile infants. J Pediatr 1993;123:17-23.
31. McCarthy PL, Sharp MR, Spiesel SZ, et al. Observation scales to identify serious illness in febrile children. Pediatrics 1982;70:802-809.
32. Teach SJ, Fleisher GR. Efficacy of an observation scale in detecting bacteremia in febrile children three to thirty-six months of age, treated as outpatients. J Pediatr 1995;126:877-881.
33. Pinkert H, Harper MB, Cooper T, et al. HIV-infected children in the pediatric emergency department. Pediatr Emerg Care 1993;9:265-269.
34. Takala AK, Jero J, Kela E, et al. Risk factors for primary invasive pneumococcal disease among children in Finland. JAMA 1995;273:859-864.
35. Kramer MS, Etezadi-Amoli J, Ciampi A, et al. Parents’ versus physician’s values for clinical outcomes in young febrile children. Pediatrics 1994;93:697-701.
36. Oppenheim PI, Sotiropoulos G, Baraff LJ. Incorporating patient preferences into practice guidelines: management of children with fever without source. Ann Emerg Med 1994;24:836-841.
37. Vukmir RB. Compliance with ED patient referral. Am J Emerg Med 1992;10:413-416.
38. Scarfone RJ, Loiselle JM, Wiley JF. Compliance with scheduled revisits to a pediatric emergency department. Acad Emerg Med 1994;1:A41. Abstract.
39. Hertz AL, Herrod HG, Barrett FF, et al. Outpatient management of selective febrile neonates with ceftriaxone and home nurse visitations. Acad Emerg Med 1994;1:A3.
40. American College of Emergency Physicians. Clinical policy for the initial approach to children under the age of 2 years presenting with fever. Ann Emerg Med 1993;22:628-637.
41. Wears RL, Stenklyft PH, Luten RC. Using decision tables to verify the logical consistency and completeness of clinical practice guidelines: Fever without a source in children under three. Acad Emerg Med 1994;1:A35.
Physician CME Questions
57. Which of the following is true concerning OB?
A. All children with OB have temperatures ³ 38°C.
B. Febrile children with otitis media and upper respiratory infections have the same rate of OB as febrile children with no source for infection.
C. Observation variables (e.g., YOS) are an accurate method for determining a child’s risk for harboring OB.
D. Children who attend day care centers have a decreased risk of developing OB.
58. Which of the following techniques will increase the speed and rate of the detection of positive blood cultures?
A. Using at least 3 mL of blood per bottle.
B. Obtaining two or more different sets of cultures
C. Use of a specialized atmospheric pressure monitors that measure any increase or decrease in internal atmospheric pressure due to gas production or use (e.g., DIFCO ESP technique)
59. All of the following may be used for identifying the presence of OB except:
A. temperature elevation.
B. blood cultures.
C. immune status.
D. use of antipyretics.
60. Untreated OB due to Streptococcus pneumoniae:
A. progresses to a serious bacterial infection in about 25% of cases.
B. progresses to meningitis in about 10% of cases.
C. causes a WBC count ³ 20,000 cells/mm3 in most cases.
D. clears spontaneously in most cases.
61. ACEP’s clinical policy for managing febrile children 1-24 months old with fever and no source includes which of the following?
A. Mandatory blood culture on all children with fever ³ 39°C
B. Urinalysis on all febrile female children with fever ³ 39°C
C. Consideration of a CBC, lumbar puncture, blood culture, and empiric treatment with antibiotics for well-appearing children with fever ³ 40°C
D. Lumbar puncture on all children less than 6 months old with temperatures ³ 40°C
62. Untreated OB due to Haemophilus influenzae:
A. progresses to a serious bacterial infection in about 25% of cases.
B. progresses to meningitis in about 25% of cases.
C. is less likely to lead to a serious bacterial infection compared to untreated S. pneumoniae OB.
D. causes a WBC count ³ 20,000 cells/mm3 in most cases.
63. At what age cut-off can the absence of meningeal signs be relied upon to exclude meningitis in a febrile child who is alert and awake?
A. 6 months
B. 12 months
C. 24 months
64. The most common organism causing OB in children who have been immunized against H. influenzae is:
A. meningococcus.
B. Escherichia coli.
C. Streptococcus pneumoniae.
D. Staphylococcus aureus.
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