Perspectives on occult bacteremia in children

Bacteremia in young children seen in the outpatient clinic is a reasonably frequent occurrence with occasionally serious sequelae; most patients, however, do quite well. The problem is more perplexing in infants and young children with high fever and no apparent focus of infection. Laboratory tests and clinical observations help to determine which children are at low risk of occult bacteremia and need not have blood cultured; testing and assessment are much less predictive of the child who does have occult bacteremia. Currently, it is unclear whether treating all patients at risk is warranted. In any case, very close follow-up of the patient who is sent home from the outpatient department with high fever is desirable. The prevalence of serious infections caused by pneumococcus, Hib, and meningococcus warrants continued research on the development of vaccines that effectively prevent these infections.     

儿童隐性菌血症研究现状及进展

儿童隐匿性菌血症（occult bacteremia,OB）是指临床仅表现为发热（通常≥39℃）,没有中毒症状及局部感染的临床或实验室证据,而血培养阳性[1]。这些OB患儿大都可以自愈,且由于外观良好常被临床忽视,如果不及时诊断和治疗,有10%-25%会发生严重细菌感染[2, 3],其中3%-6%发展为脑膜炎[4],还会出现肺炎、化脓性关节炎、骨髓炎、败血症甚至死亡。我国仅有几篇关于OB的病例报道[5],缺乏关于OB流行病学研究及相关资料。本文就儿童隐性菌血症的研究现状和进展进行综     

Factors predicting occult bacteremia in young children

A febrile child without a definite localizing sign of infection may be in initial phase of bacteremia which unless treated would result in systemic complication. These instances are referred to as “Occult bacteremia”. The common pathogens isolated in these children areStreptococcus pneumoniae, Hemophilus influenzae andNeisseria meningitidis. A hundred consecutive children in the age group of 3–36 months attending pediatric outpatient department and casualty were clinically evaluated using AIOS (acute illness observation scale) score and were subjected to complete blood counts, smear for malarial parasites, ESR and blood culture. In the 19-month study period, 4 instances of occult bacteremia were identified.Streptococcus pneumoniae was cultured in 3 cases andH. influenzae in one. A febrile and toxic child in the age group of 3–36 months has a high risk of occult bacteremia. High fever of temperature ≥ 102°F, ESR ≥ 15 mm/hour, and total leukocyte count ≥ 15,000 / mm³, in a child with AIOS score of ≥ 10 may be considered for more detailed investigations and early intervention with antimicrobial therapy.     

Parents' utilities for outcomes of occult bacteremia

OBJECTIVE: To describe parents' values for outcomes of occult bacteremia using utility assessment, a quantitative method that incorporates risk preference. DESIGN: Computer-based utility assessment interview. SETTING: Urban children's hospital pediatric emergency department with 50 000 visits annually. PARTICIPANTS: Convenience sample of parents presenting with a child between 3 and 36 months. MAIN OUTCOME MEASURE: Parents' utility values for 8 outcomes from treatment of occult bacteremia: blood drawing, localized infection, hospitalization for antibiotics, meningitis with recovery, meningitis resulting in deafness, minor brain damage, severe brain damage, and death. RESULTS: Ninety-four subjects successfully completed the interview. Mean utilities were 0.9974 for blood drawing, 0.9941 for local infection, 0.9921 for hospitalization, 0.9768 for meningitis with recovery, 0.8611 for deafness, 0.7393 for minor brain damage, 0.3903 for severe brain damage, and 0.0177 for death. All values were significantly different from those that immediately preceded and succeeded (P<.0001), except for local infection vs hospitalization (P = .14). Median utilities for blood drawn, local infection, and hospitalization were 1. There were no significant differences among utilities of parents who presented with a febrile child (temperature > or =39 degrees C), or an afebrile child (temperature <39 degrees C). There were also no significant differences among utilities regardless of whether parents had children with prior experience with the outcomes. CONCLUSIONS: Assessment of utilities for outcomes of occult bacteremia yielded extremely high mean and median values for outcomes without permanent sequelae. This suggests that parents presenting to an emergency department may rationally prefer painful transient experiences, including venipuncture, for their children rather than risk even rare chances of severe outcomes.     

Follow-up of patients with occult bacteremia in pediatric emergency departments.

Blood cultures are frequently obtained in pediatric emergency departments (EDs) from febrile young children at risk for bacteremia and subsequent development of serious bacterial infections. This study of 105 children with occult bacteremia treated in two large urban pediatric EDs describes the follow-up of these patients and the impact that positive blood culture results have on the detection of serious illness. Seventy-seven percent of patients had a follow-up visit in the ED, 8% had follow-up by telephone alone, and 15% were not contacted. Of the patients who returned to the ED, 49% did so because they were notified of the positive blood culture result. The mean time interval for these patients from registration at the initial visit to report of positive blood culture result was 30.0 hours and, from registration at the initial visit to follow-up visit, was 42.7 hours. Thirty-seven percent of those who returned did so because a follow-up visit was scheduled at the initial encounter, and 13% returned because of persistent illness. Ten children (9.6%), five of whom had been notified of the positive blood culture, returned with serious illnesses. Patients whose diagnosis of serious illness was facilitated by blood culture results had shorter delay in identifying cultures as positive than did patients notified of positive results who did not develop serious illness (16.2 vs 31.6 hours; P < 0.05). The delay in follow-up of children with occult bacteremia limits the usefulness of blood cultures in the early detection of serious illness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk factors for development of bacterial meningitis among children with occult bacteremia

To identify risk factors for the development of bacterial meningitis, we compared clinical characteristics in children with occult bacteremia who did and those who did not subsequently develop bacterial meningitis. The estimates of risk were adjusted for the possible confounding effects of other characteristics by using logistic regression. Of 310 children (median age 15 months) who had occult bacteremia with Streptococcus pneumoniae, Haemophilus influenzae type b, or Neisseria meningitidis at either Yale-New Haven Hospital or Children's Hospital of Pittsburgh, bacterial meningitis subsequently developed in 22 (7%). Compared with the risk associated with occult bacteremia with S. pneumoniae, the adjusted relative risk for bacterial meningitis was 85.6 (P less than 0.0001) and 12.0 (P = 0.0001) for N. meningitidis and H. influenzae type b, respectively. By contrast, the adjusted relative risk associated with a lumbar puncture at the initial visit was only 1.2 (P = 0.78). The development of bacterial meningitis in children with occult bacteremia is strongly associated with the species of bacteria that causes the infection, but not with a lumbar puncture or with other clinical characteristics identifiable at the initial visit.     

Management of infants at risk for occult bacteremia: a decision analysis

Because febrile infants with no obvious source of bacterial infection may have bacteremia, and because bacteremia is difficult to diagnose on clinical grounds, we used decision analysis to evaluate whether such infants should be treated with antibiotics, tested further, or sent home. Using a simple decision tree, we found that the decision to give empiric antibiotic treatment is the decision of choice. The difference in quality-adjusted life expectancy between the "best" and "worst" decisions was only 11 days. However, this difference translated to prevention of death or permanent disability in 60 cases per 100,000 febrile children. Further, empiric treatment remained the best management alternative unless the probability of bacteremia was less than 1.4% (less than any published prevalence), or the efficacy of treatment was less than 21%. Our analysis demonstrated that a test with far greater sensitivity than leukocyte count or other tests currently in use is needed to justify testing rather than treating empirically. Further, an enormous patient population would be needed to find a difference of both clinical and statistical significance between treated and untreated patients in a controlled trial. In the absence of such trials, we recommend blood culture and empiric antibiotic treatment of all infants at risk for occult bacteremia.     

Resource utilization and contaminated blood cultures in children at risk for occult bacteremia

OBJECTIVE: To measure the increases in resource utilization and hospital charges associated with the evaluation of contaminated blood cultures obtained from emergency department patients at risk for occult bacteremia. DESIGN: Retrospective medical record review. SETTING: Emergency department of an urban, university-affiliated pediatric referral center. PATIENTS: Children aged 3 to 36 months with blood cultures positive for bacterial growth obtained between January 1994 and October 1996. MAIN OUTCOME MEASURES: Increased resource utilization related to contaminated blood culture follow-up, including telephone contact, return emergency department visits, additional diagnostic tests and therapies performed at reevaluation, and hospital admissions. Hospital charges for these additional services were tabulated. RESULTS: Of 8,306 children who had blood cultures drawn, 491 (5.9%) had positive findings. Four hundred eighty-five (98.8%) of these were available for review. Two hundred seventy-six (57%) of 485 were excluded from final analysis. Of the remaining 209 patients at risk for occult bacteremia, 85 (41%) had cultures that grew contaminants only. Follow-up of these 85 patients generated 106 telephone calls, 49 return visits to the emergency department, 102 additional diagnostic tests, 18 doses of parenteral antibiotics, and 12 hospital admissions with a combined length of stay of 24 days. This resulted in additional charges of $78,904, or an additional $642 per true pathogen recovered. CONCLUSIONS: Contaminated blood cultures obtained from children at risk for occult bacteremia lead to substantial increases in resource utilization and hospital charges. These untoward effects should be accounted for in formal decision analyses regarding the management of occult bacteremia.     

Temperature response to acetaminophen and risk of occult bacteremia: a case-control study

A case-control study of 34 children with occult bacteremia was conducted to test the hypothesis that nonresponse to acetaminophen (decrease less than or equal to 0.8 degrees C) is a risk factor for occult bacteremia. Febrile children visiting the emergency center from May 1986 to October 1987 were monitored for occult bacteremia. Inclusion criteria were age 2 months to 6 years, temperature greater than or equal to 38.9 degrees C, and having a blood culture. Exclusion criteria were serious acute or chronic illness, sponging for fever reduction, current therapy with antibiotics or steroids, and admission to the hospital. Records of 3892 febrile children were reviewed. Of these, 2101 (54%) had a blood culture and 1028 (26%) were eligible. All patients (positive blood culture) were matched with two control subjects (negative blood culture). Patients and control subjects had similar age, gender, ethnicity, height of initial temperature, time to second temperature, and dose of acetaminophen. The estimated risk of occult bacteremia for nonresponders was 9.2 (95% confidence interval 2.7, 32.0). We conclude that children who do not respond to acetaminophen by at least a 0.8 degrees C decrease in temperature have an increased risk of occult bacteremia. However, achieving a response to acetaminophen does not eliminate the possibility that the child has occult bacteremia.     

Outcome of children with occult bacteremia caused by Haemophilus influenzae type b.

For better definition of the clinical course and outcome of children with occult bacteremia caused by Haemophilus influenzae type b (Hib), we reviewed the medical records of children who were initially managed as outpatients and subsequently found to be bacteremic. At Yale-New Haven Hospital (1971 to 1987) and the Children's Hospital of Philadelphia (1982 to 1987), 69 previously healthy children were identified with occult Hib bacteremia. Their median age was 14 months (range, 4 to 89 months). Thirty-six (52%) of the 69 were either febrile and/or had a focus of serious infection at follow-up (meningitis (17), pneumonia (5), epiglottitis (3), cellulitis (5), and septic arthritis (3)). Although the remaining 33 children (48%) were afebrile and appeared well on reevaluation, 3 of these 33 were still bacteremic and another 5 subsequently developed focal Hib infections. These 8 children were significantly younger (median age, 8.5 months) than the 25 children who remained well (median age, 16 months; P = 0.03). Of the 28 children who had initially been treated with antimicrobials to which their organism was known to be susceptible, 12 (43%) were improved at reevaluation and remained well; 7 (23%) of the 31 patients who had not received such antimicrobials improved and remained well (P = 0.17). Children initially managed as outpatients and later found to have had Hib bacteremia are at risk of subsequently developing a serious focal infection.     

Pneumococcal and Haemophilus influenzae type b antigen detection in children at risk for occult bacteremia

We prospectively evaluated pneumococcal and Haemophilus influenzae type b antigen detection in serum and urine of young (3 to 30 months of age) febrile (temperature greater than or equal to 39 degrees C) children at risk for occult bacteremia. Patients with septic shock, meningitis, or epiglottitis were excluded. Of 576 patients, 16 had pneumococcal bacteremia (final diagnoses: primary bacteremia, nine; otitis media, four; pneumonia, two; unknown, one), and five had H influenzae b bacteremia (final diagnoses: primary bacteremia, two; cellulitis, two; arthritis, one). Latex agglutination was positive in all five patients with H influenzae b bacteremia (positive in three of three urine specimens, three of four sera tested) but only one of 16 patients with pneumococcal bacteremia (positive in one of seven urine samples, zero of 13 sera tested). Both assays had specificities of greater than 95%. Nonspecific agglutination occurred in 7% of specimens tested. Enzyme immunoassay for pneumococcal antigen, although more sensitive than latex agglutination, failed to detect antigen in ten sera and three urine specimens from patients with pneumococcal bacteremia. Thus, neither latex agglutination nor enzyme immunoassay was sufficiently sensitive for detection of occult pneumococcal bacteremia. Latex agglutination for H influenzae b holds promise as a sensitive and specific test for rapid diagnosis of occult bacteremia due to H influenzae b.     

Strategies for diagnosis and treatment of children at risk for occult bacteremia: clinical effectiveness and cost-effectiveness

Decision analysis was used to evaluate the probable health benefits, complications, and costs of six management strategies for febrile children at risk for occult bacteremia. The strategy that combined blood culture with empiric oral antibiotic treatment for all patients was predicted to prevent the highest number of major infections and to have the lowest cost per major infection prevented. The strategy that combined a leukocyte count and blood culture for all patients, followed by empiric antibiotic treatment for those with leukocyte count greater than or equal to 10,000/mm3, had almost equal cost and clinical effectiveness and avoided many antibiotic complications. Culture of blood specimens from all patients and no empiric treatment constituted the third most clinically effective intervention but was the least cost-effective in this model. Giving a 2-day oral course of amoxicillin without testing had the lowest average cost per febrile patient but was the least clinically effective intervention. However, the low degree of effectiveness of empiric treatment alone was based on the assumption that oral amoxicillin therapy was only 20% effective in preventing major infections after bacteremia. At higher estimates of effectiveness, treatment alone became a more viable strategy. We conclude that approaches which combine blood culture with empiric antibiotic treatment are the most clinically effective and the most cost-effective strategies for children at risk for occult bacteremia.     

The febrile child-missed meningitis and bacteremia

Children with fever often present to the emergency department (ED) for cart. Most have self-limited viral infections; some have life-threatening bacterial infections. Misdiagnosis of children with sepsis and meningitis are among the most common and most costly course for medical malpractice suits in emergency medicine. Unfortunately, there are no foolproof guidelines to prevent error in diagnosing a febrile child. Physicians are advised to use great caution if a febrile infant remains irritable and has persistent vomiting or lethargy during evaluation in the ED. If a patient does not seem improved after a period of observation and perhaps dehydration, hospital admission and empirical antibiotics arc recommended. Use particular caution when evaluating a child with fever and a petechial rash. Meticulous documentation of care provided to febrile infants and children may prevent a lawsuit in the cent of a poor outcome. In addition, it is imperative to arrange follow-up within 12 to 24 hours when there is concern about a baby's condition or when an infant's illness warranted a sepsis work-up. A follow-up phone call to the child's family may help clarify instructions and identify problems. Febrile patients who return to the ED for additional care should be carefully re-examined.