Occult Pneumococcal Bacteremia Research Articles

Febrile seizures with leukocytosis as a predictor for occult bacteremia.

Febrile children 3-36 months old, who had a body temperature >39°C and white blood cell (WBC) count >15000/mm3 were known to be at risk for occult pneumococcal bacteremia (OPB) in the pre-pneumococcal conjugate vaccine (PCV) era. The positive predictive value of these criteria, however, decreased dramatically after the introduction of PCV, indicating a need for alternative criteria. A high rate of febrile seizures has been noted in children with OPB, suggesting that screening may still be practical in this population. We performed a retrospective analysis to evaluate factors that predict OPB in patients visiting the emergency department (ED) with febrile seizures. Children 3-36 months old who visited the ED for febrile seizures and had blood cultures taken were included. Patients with underlying diseases were excluded from analysis. We performed statistical analyses comparing patient demographics according to the presence or absence of OPB. One thousand and eighty-two patients visited the ED with febrile seizure, and blood cultures were taken in 397, of whom 87% had received more than three doses of PCV. Of the nine patients with OPB, eight (89%) met the risk criteria. In contrast, only 12% (48/388) of those without OPB met the criteria. In this population, those who fulfilled the risk criteria were more likely to have OPB than those who did not (14.3% vs 0.3%; likelihood ratio, 7.17). High WBC count and fever may effectively predict OPB in pediatric patients with febrile seizure in the post-PCV era.

Occult Pneumococcal Bacteremia

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.

Recurrence of occult pneumococcal bacteremia by an identical strain in an apparently healthy child

This is the first report to describe an apparently healthy girl, who developed recurrent occult bacteremia by the same Streptococcus pneumoniae strain, at 11 and 15 months of age. The two separately isolated organisms were demonstrated to have the identical serotype (type 6B), antibiotic susceptibility (intermediately penicillin-resistant), genotypes of penicillin-binding proteins, and patterns of pulse-field gel electrophoresis. The serum levels of anti-type 6B antibodies showed poor responses after both bacteremic episodes, but other immunological workups did not demonstrate any abnormalities. This case indicates that occult bacteremia may recur due to an identical pneumococcal strain in an immunocompetent infant, and that early introduction of pneumococcal conjugate vaccine is necessary in Japan.

Management of Febrile Children in the Age of the Conjugate Pneumococcal Vaccine: A Cost-Effectiveness Analysis

The optimal practice management of highly febrile 3- to 36-month-old children without a focal source has been controversial. The recent release of a conjugate pneumococcal vaccine may reduce the rate of occult bacteremia and alter the utility of empiric testing and treatment. The objective of this study was to determine the cost-effectiveness of 6 different management strategies of febrile 3- to 36-month-old children at current and declining rates of occult pneumococcal bacteremia. A cost-effectiveness (CE) analysis was performed to compare the strategies of "no work-up," "clinical judgment," "blood culture," "blood culture + treatment," "complete blood count (CBC) + selective blood culture and treatment," and "CBC and blood culture + selective treatment." A hypothetical cohort of 100 000 children who were 3 to 36 months of age and had a fever of >/=39 degrees C and no source of infection was modeled for each strategy. Our main outcome measures were cases of meningitis prevented, life-years saved compared with "no work-up," total cost (1999 dollars), and incremental CE ratios. When compared with "no work-up," the strategy of "CBC + selective blood culture and treatment" using a white blood cell (WBC) cutoff of 15 x 10(9)/L prevents 48 cases of meningitis, saves 86 life-years per 100 000 patients, and is less costly at the current rate of bacteremia (1.5%). Using the strategy of "CBC + selective blood culture and treatment" with a lower WBC cutoff of 10 x 10(9)/L costs an additional $72 300 per life-year saved. If the rate of bacteremia declines to 0.5%, then the incremental CE ratio of "clinical judgment" compared with "no work-up" is $38 000 per life-year saved; however, strategies that include empiric testing or treatment result in CE ratios greater than $300 000 per life-year saved. "CBC + selective blood culture and treatment" using a WBC cutoff of 15 x 10(9)/L is cost-effective at the current rate of pneumococcal bacteremia. If the rate of occult bacteremia falls below 0.5% with widespread use of the conjugate pneumococcal vaccine, then strategies that use empiric testing and treatment should be eliminated.

Serotype Prevalence of Occult Pneumococcal Bacteremia

The licensure and use of a pneumococcal conjugate vaccine that is immunogenic in children who are younger than 2 years may affect the epidemiology of occult bacteremia. This study was conducted to determine the serotype prevalence of Streptococcus pneumoniae isolates from children with occult bacteremia and to document the proportion that would be covered by the recently licensed heptavalent pneumococcal conjugate vaccine. A cohort of 5901 children who were 2 to 24 months of age and had a temperature of >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department was studied to determine the prevalence of S pneumoniae serotypes. Patients were excluded if their immune system was suppressed, they had a diagnosis of a focal infection, they were evaluated by lumbar puncture, they were admitted to the hospital, or they died during initial evaluation. Blood cultures were inoculated into pediatric blood culture bottles and processed using an automated carbon dioxide monitoring system. All pneumococcal isolates were serotyped on the basis of capsular swelling with type-specific antisera (Quellung reaction). The study population consisted of 5901 patients. The overall rate of occult bacteremia was 1.9% (95% confidence interval [CI]: 1.5-2.3). S pneumoniae accounted for 92 of 111 isolates (82.9%; 95% CI: 74.6-89.4) in children with occult bacteremia. Eight pneumococcal serotypes were represented: 6A (2%), 9V (6%), 19F (6%), 18C (8%), 4 (9%), 6B (13%), 23F (15%), and 14 (42%). Serotypes 14, 6B, and 23F accounted for 69.3% (95% CI: 58.6-78.7) of typed isolates. In the cohort, 97.7% (95% CI: 92-99.7) of isolated serotypes are represented in the newly licensed heptavalent pneumococcal conjugate vaccine. The single isolated serotype that would not have been covered by the currently licensed heptavalent pneumococcal conjugate vaccine was 6A. S pneumoniae accounts for the vast majority of bacterial pathogens in children with occult bacteremia. As indicated by the results of this study, the heptavalent pneumococcal conjugate vaccine may prevent the majority of occult pneumococcal bacteremia episodes. The 2 cases of bacteremia with a serotype that would not have been included in the vaccine both were due to serotype 6A. It has been noted that there is potential nonvaccine serotype and subgroup cross-protection (6A from 6B) afforded to children who are immunized with the heptavalent vaccine. The high potential efficacy of the heptavalent pneumococcal conjugate vaccine for strains that cause occult bacteremia in our population may have a profound effect on the treatment of children with fever without a source. There has been an alarming and rapid emergence of antibiotic-resistant pneumococcal strains. Less pressure to use broad-spectrum antibiotics, which in turn causes further antibiotic resistance, should result. Laboratory testing and hospitalization also should be reduced. The prevalence rates determined by this study may be used as baseline data for comparison of serotype rates of occult pneumococcal bacteremia after widespread use of the heptavalent vaccine.

Management of fever without source in infants and children

Twenty percent of febrile children have fever without an apparent source of infection after history and physical examination. Of these, a small proportion may have an occult bacterial infection, including bacteremia, urinary tract infection (UTI), occult pneumonia, or, rarely, early bacterial meningitis. Febrile infants and young children have, by tradition, been arbitrarily assigned to different management strategies by age group: neonates (birth to 28 days), young infants (29 to 90 days), and older infants and young children (3 to 36 months). Infants younger than 3 months are often managed by using low-risk criteria, such as the Rochester Criteria or Philadelphia Criteria. The purpose of these criteria is to reduce the number of infants hospitalized unnecessarily and to identify infants who may be managed as outpatients by using clinical and laboratory criteria. In children with fever without source (FWS), occult UTIs occur in 3% to 4% of boys younger than 1 year and 8% to 9% of girls younger than 2 years of age. Most UTIs in boys occur in those who are uncircumcised. Occult pneumococcal bacteremia occurs in approximately 3% of children younger than 3 years with FWS with a temperature of 39.0°C (102.2°F) or greater and in approximately 10% of children with FWS with a temperature of 39.5°C (103.1°F) or greater and a WBC count of 15,000/mm3 or greater. The risk of a child with occult pneumococcal bacteremia later having meningitis is approximately 3%. The new conjugate pneumococcal vaccine (7 serogroups) has an efficacy of 90% for reducing invasive infections of Streptococcus pneumoniae. The widespread use of this vaccine will make the use of WBC counts and blood cultures and empiric antibiotic treatment of children with FWS who have received this vaccine obsolete. [Baraff LJ. Management of fever without source in infants and children. Ann Emerg Med. December 2000;36:602-614.]

Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome.

To evaluate selected characteristics of occult bacteremia in the post-Haemophilus influenzae type b (HIB) vaccine era. A retrospective cohort study was performed involving 5901 children 2 to 24 months old with fever >/=39.0 degrees C evaluated with a blood culture at an urban tertiary care children's hospital emergency department (ED) between February 1993 and June 1996. Patients were excluded if immune-suppressed, diagnosed with a focal infection, evaluated by lumbar puncture, or admitted to the hospital during initial evaluation. Prevalence of occult bacteremia, distribution of current pathogenic organisms, and time to positive culture in a continuously monitored system were determined. All patients with cultures positive for pathogenic bacteria were reevaluated and serious adverse outcomes were documented. The prevalence of occult bacteremia was 1.9% (95% confidence interval: 1.5%-2.3%). Streptococcus pneumoniae accounted for 82.9% of all pathogens and H influenzae was not a causative organism in this cohort. The mean time to positive culture was significantly shorter for pathogens compared with contaminants (14.9 hours vs 31.1 hours). A culture that was positive in </=18 hours was 13.0 (6.3-26. 6) times more likely to contain a pathogen than a contaminant. The average time from positive culture notification to reevaluation in the ED was 10.6 hours and over half of the patients recalled to the ED for positive cultures were admitted to the hospital. Of patients with occult pneumococcal bacteremia, 95.7% had resolution of their bacteremia without the use of parenteral antibiotics. Two patients had serious adverse outcomes. The rate of meningitis or death was. 03% (.004%-.12%). The contamination rate of blood cultures was 2.1% (1.7%-2.5%). Most (85%) of these patients were reevaluated in the ED and more than one third were admitted to the hospital before full identification of the organism. Prevalence of occult bacteremia in the post-HIB vaccine era is lower than previously reported. S pneumoniae is the most common causative organism and resolves without parenteral antibiotics in the vast majority of cases. Continuously monitoring blood culture systems allow for early identification and can aid in differentiating contaminated from true pathogenic cultures by time to positive culture. Serious adverse outcome is an uncommon result of occult bacteremia. Updated epidemiology and microbiologic technology may impact the evaluation and treatment of children at risk for occult bacteremia.

OCCULT BACTEREMIA IN YOUNG FEBRILE CHILDREN

The evaluation of nontoxic-appearing, young, febrile children has been a subject of considerable debate. Of young, nontoxic-appearing children aged 3 to 36 months with temperatures of 39 degrees C or more and no clear source, approximately 2% to 3% have occult bacteremia. Of these bacteremias, approximately 90% are caused by S. pneumoniae, 5% by nontyphoidal Salmonella sp., and 1% by N. meningitidis. Most children with occult pneumococcal bacteremia improve spontaneously, but approximately 25% of untreated patients have persistent bacteremia or develop new focal infections, including 3% to 6% who develop meningitis. Occult meningococcal bacteremia, although rare, has frequent complications, including meningitis in approximately 40% and death in approximately 4%. Less is known about the natural history of untreated occult nontyphoidal Salmonella bacteremia. Empiric antibiotic treatment of children with occult bacteremia decreases the rate of complications, including meningitis. Few disagree that febrile, young children at risk for occult bacteremia require a careful clinical evaluation and close follow-up. The benefits of laboratory screening and selective empiric antibiotic treatment of febrile children at risk for occult bacteremia have to be weighed against the costs of screening tests and blood cultures, inconvenience, temporary discomfort to patients, risk for side effects of antibiotics, and the role of antibiotics in the development of bacterial resistance. Although great debate exists concerning the role of empiric antibiotics, a strategy for obtaining blood cultures and empirically administering antibiotics on the basis of an increased ANC, in addition to close clinical follow-up, may be effective in reducing the frequency and severity of uncommon but adverse sequelae. A highly effective S. pneumoniae bacterial conjugate vaccine will soon be available, which will benefit all children, and will alter the ways that clinicians evaluate fully immunized young, febrile children.

Predicting Pneumococcal Bacteremia in Febrile Children

Occult pneumococcal bacteremia (OPB) occurs in up to 3% of children under 3 years old with temperatures above 39°C; if untreated, 10% to 25% of these

Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era.

To determine the risk for bacteremia, in the post-Haemophilus influenzae type b era, in a prospective cohort of well-appearing febrile children 3 to 36 months of age with no obvious source of infection; and to compare the predictive abilities of objective criteria in identification of children with occult pneumococcal bacteremia from those at risk. All children seen from 1993 through 1996, 3 to 36 months of age with a temperature of 39.0 degrees C or higher, no identified source of infection (except otitis media), and discharged to home were considered to be at risk for occult bacteremia and included in the study. Urban pediatric emergency department. Of 199868 patient visits to the emergency department, 1911 children were considered to be at risk for occult bacteremia. Blood cultures were obtained from 9465 (79%). A total of 149 blood cultures contained pathogenic organisms, indicating a rate of occult bacteremia of 1.57% (95% confidence intervals: 1.32%-1.83%). White blood cell count and absolute neutrophil count were the best predictors for occult pneumococcal bacteremia. Using a white blood cell count cutoff value of 15 cells x 10(9)/L (sensitivity, 86%; specificity, 77%; and positive predictive value, 5.1%) would result in the treatment of approximately 19 nonbacteremic children for each bacteremic child treated. The prevalence of occult bacteremia in children 3 to 36 months old with temperatures of 39.0 degrees C or higher and no obvious source of infection is 1.6%. The white blood cell and absolute neutrophil counts are the most accurate predictors of occult pneumococcal bacteremia and when available should be used if presumptive antibiotic therapy is being considered.

Predictors of Occult Pneumococcal Bacteremia in Young Febrile Children

Study objective: Occult pneumococcal bacteremia (OPB) occurs in 2.5% to 3% of highly febrile children 3 to 36 months of age, and 10% to 25% of untreated patients with OPB experience complications, including 3% to 6% in whom meningitis develops. The purpose of this study was to identify predictors of OPB among a large cohort of young, febrile children treated as outpatients using multivariable statistical methods. Methods: We derived and validated a logistic regression model for the prediction of OPB. We evaluated 6,579 outpatients 3 to 36 months of age with temperatures of 39° C or higher who previously had been enrolled in a study of young febrile patients at risk of OPB in the emergency departments of 10 hospitals in the United States between 1987 and 1991; 164 patients (2.5%) had OPB. We randomly selected two thirds of this population for the derivation of the model and one third for validation. In the derivation set, we analyzed the univariate relationships of six variables with OPB: age, temperature, clinical score, WBC count, absolute neutrophil count (ANC), and absolute band count (ABC). All six variables were then entered into a logistic regression equation and those retaining statistical significance were considered to have an independent association with OPB. Results: Patients with OPB were younger, more frequently ill-appearing, and had higher temperatures, WBC, ANC, and ABC than patients without bacteremia. Only three variables, however, retained statistically significant associations with OPB in the multivariate analysis: ANC (adjusted odds ratio [OR] 1.15 for each 1,000 cells/mm 3 increase, 95% confidence interval [CI] 1.06, 1.25), temperature (adjusted OR 1.77 for each 1° C increase, 95% CI 1.21, 2.58), and age younger than 2 years (adjusted OR 2.43 versus patients 2 to 3 years old, 95% CI interval 1.11, 5.34). In the derivation set, 8.1% of patients with ANCs greater than or equal to 10,000 cells/mm 3 had OPB (95% CI 6.3, 10.1%) versus .8% of patients with ANCs less than 10,000 cells/mm 3 (95% CI .5, 1.2%). When tested on the validation set, the model performed similarly. Conclusion: Independent predictors of OPB in children 3 to 36 months of age with temperatures of 39° C or higher treated as outpatients include ANC, temperature, and age younger than 2 years. These predictors may be used to develop clinical strategies to limit laboratory testing and antibiotic administration to those children at greatest risk of OPB. [Kuppermann N, Fleisher GR, Jaffe DM: Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med June 1998;31:679-687.]

Occult pneumococcal bacteremia

There is little information on the outcome of occult pneumococcal bacteremia in children who appear well at the time of first reevaluation. To determine the outcome of such children we reviewed the medical records of 364 children with blood cultures positive for Streptococcus pneumoniae managed at 2 hospitals in New Haven from 1973 to 1987. One hundred eighty of the 364 children were initially managed as outpatients; 111 of the 180 (62%) were afebrile and appeared well at the first reevaluation. Twenty-two of these 111 children (20%) were hospitalized and treated with intravenously administered antimicrobials at the first reevaluation visit; 2 of these 22 were still bacteremic, although no focal infection was found. Seventy-eight children (70%) were sent home after the first reevaluation visit with orally administered antimicrobials; 1 of these 78 children was still bacteremic and another subsequently was found to have meningitis that had been present at the first visit (culture of the cerebrospinal fluid obtained at the first visit subsequently grew S. pneumoniae). Eleven children (10%) were sent home from the reevaluation visit without antimicrobial treatment and none had persistent or recurrent pneumococcal infection. We conclude that the child who is afebrile and appears well at reevaluation for a blood culture positive for S. pneumoniae is unlikely to develop serious sequelae. Outpatient management with careful follow-up is essential for such children.

潜在性肺炎双球菌菌血症の3例

潜在性肺炎双球菌菌血症の3例

Occult Bacteremia in Children With Simple Febrile Seizures

Sir.—The association of bacteremia and febrile seizures described by Chamberlain and Gorman1in a recentAJDCarticle has been recognized at least since 1967, when two of three patients with pneumococcal bacteremia described by Belsey2presented with seizures. Five of 11 children with occult pneumococcal bacteremia described in 19703presented with seizures, and all had sterile cerebrospinal fluid. As Chamberlain and Gorman point out, obtaining blood cultures should always be considered for children with febrile seizures. We should recall that children with pneumococcal bacteremia, with or without seizures, who have sterile cerebrospinal fluid initially may go on to develop meningitis, while receiving oral or even parenteral antibiotics.2

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.

Simultaneous occult pneumococcal bacteremia in identical twins

Simultaneous occult pneumococcal bacteremia in identical twins

Blood Cultures in Pediatric Practice

Occult pneumococcal bacteremia in infants was recognized as an entity a decade ago, 1.2 but the frequency of its occurrence was not appreciated until Klein and his associates at the Boston City Hospital (BCH) studied 600 consecutive febrile outpatients younger than 2 years of age. 3 They documented bacteremia in 3.2% of them, with Streptococcus pneumoniae the pathogen in nearly 80%. Subsequently, they documented the development of meningitis in 4% of the infants with unsuspected pneumococcemia. 4 Two risk factors, a rectal temperature ≥ 38.9 °C and a WBC count > 15,000/cu mm, present together in only 28% of the patients, were recognized to identify 79% of those with positive blood cultures. The following display presents rates from the BCH data: Of 1,000 febrile infants younger than 2 years of age, 769 have rectal temperature ≥ 38.9 °C. Of these 769 infants, 287 have WBC counts > 15,000/cu

Elevated parathyroid hormone levels in association with rhabdomyosarcoma

in one of our patients) may not be detected by any blood culture system i f a small volume of blood is sampled. It is likely that the four cases of pneumococcemia were detected only by routine cultures because the routine culture bottles received a larger inoculum of blood than did the quantitative plates. In our small series, colony counts were not helpful in predicting which children with occult pneumococcal bacteremia would develop sustained bacteremia or focal complications. Of the five patients with occult bacteremia, the two with 0.5 and 200 cfu/ml, respectively, subsequently developed bilateral otitis, the patient with 8 cfu/ml developed otitis and sustained bacteremia, the patient with 10 cfu /ml developed otitis and pneumonia , and the patient with 60 cfu /ml recovered uneventfully without developing focal complications. In summary; quantitative blood cultures are a sensitive technique for the early detection of childhood bacteremia. The low number of pneumococci found in the blood of some children suggests that pneumococcemia may be missed if small volumes of blood are cultured.

Complications of occult pneumococcal bacteremia in children

Children with occult pneumococcal bacteremia have not been considered to be at significant risk of developing complications. However, three of seven children, without an apparent source of pneumococcal bactermia, developed meningitis after a period of well-being, and two others developed an identifiable respiratory focus of infection. Meningitis occurred in spite of oral or low-dose intravenous penicillin therapy. We conclude that the identification of occult pneumococcal bacteremia places the child at significant risk to develop serious sequelae and that initiation of high-dose parenteral penicillin therapy, as in the treatment of pneumococcal meningitis, is indicated.