Management of febrile children in the age of the conjugate pneumococcal vaccine: a cost-effectiveness analysis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: "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.

Lack of reduction in hospitalizations and emergency department visits for varicella in the first 2 years post-vaccine licensure.

OBJECTIVES: To describe and compare the incidence and spectrum of complications of varicella pre-vaccine and post-vaccine licensure. METHODS: We performed a retrospective chart review of children under age 21 years either treated in the emergency department (ED) or admitted to the hospital with varicella at Children's Hospital, Boston, from January to December 1994 (pre-licensure) and from January 1996 to December 1997 (post-licensure). RESULTS: We identified 937 children who made a visit to the ED for varicella and 270 children hospitalized for varicella during the 3-year study period. The ratio of varicella-related visits to the ED to total visits (0.67%) did not vary significantly from the post-vaccine ratio (0.60%). The most common reasons for a visit were cellulitis in immunocompetent patients and treatment with varicella zoster immune globulin (VZIG) in children with immunosuppression. Similarly, the ratio of varicella-related hospitalizations to total hospitalizations did not vary in the pre-vaccine (0.53%) and post-vaccine (0.47%) eras. The most common complications in hospitalized patients were cellulitis in previously healthy children (37%) and uncomplicated varicella in immunocompromised patients (36%). The distribution of diagnoses in the ED and complications among hospitalized children did not differ significantly in the pre-vaccine and post-vaccine eras. CONCLUSIONS: Despite licensure of the varicella vaccine, varicella-related hospitalizations and ED visits have not changed significantly. Further efforts are needed to increase utilization of the varicella vaccine.

Accuracy of a noninvasive temporal artery thermometer for use in infants.

OBJECTIVES: To assess the accuracy of a new noninvasive temporal artery (TA) thermometer in infants; to compare the accuracy of the TA thermometer with that of a tympanic thermometer, using rectal thermometry as the criterion standard; and to compare the tolerability of the TA thermometer with that of the tympanic and rectal thermometers. DESIGN: Prospective evaluation of the accuracy of TA and tympanic thermometry, using rectal thermometry as the criterion standard. SETTING: Emergency department of an urban pediatric hospital. SUBJECTS: Convenience sample of 304 infants younger than 1 year presenting for care. MAIN OUTCOME MEASURES: Temperatures were measured using TA, tympanic, and rectal thermometers for all infants. Agreement between TA or tympanic and rectal temperatures was assessed. The sensitivity and specificity of TA or tympanic thermometers for detecting rectal fever were determined. Discomfort scores, using a standardized scale, were assessed by trained observers after each temperature measurement was made. RESULTS: Linear regression analysis of the relation between TA and rectal temperatures yielded a model with a slope of 0.79 (vs a slope of 0.68 for tympanic vs rectal temperature; P =.02) and an r of 0.83 (vs r = 0.75 for tympanic vs rectal temperature; P<.001). Among 109 patients with a rectal temperature of 38 degrees C or higher, the TA thermometer had a sensitivity of 0.66 compared with the tympanic thermometer's sensitivity of 0.49 (P<.001). Discomfort scores with TA thermometry were significantly lower than with rectal thermometry (P =.007). CONCLUSIONS: The TA thermometer has limited sensitivity for detecting cases of rectal fever in infants. However, the TA thermometer is more accurate than the tympanic thermometer in infants, and it is better tolerated by infants than rectal thermometry.

Meningococcal disease among children who live in a large metropolitan area, 1981-1996.

Neisseria meningitidis is an important cause of serious bacterial infections in children. We undertook a study to identify meningococcal infections of the blood, cerebrospinal fluid, or both of children in a defined geographic area to describe the burden of disease and the spectrum of illness. We reviewed the medical records of all children aged <18 years who had meningococcal infections at the 4 pediatric referral hospitals in Boston, Massachusetts, from 1981 through 1996. We identified 231 patients with meningococcal disease; of these 231 patients, 194 (84%) had overt disease and 37 (16%) had unsuspected disease. Clinical manifestations included meningitis in 150 patients, hypotension in 26, and purpura in 17. Sixteen patients (7%) died. Although meningococcal disease is devastating to a small number of children, we found that the burden of pediatric disease that it caused at the 4 pediatric referral centers in this geographic region was limited; that patients with overt meningococcal disease are most likely to have meningitis; and that individual practitioners are unlikely to encounter a patient with unsuspected meningococcal disease.

Potential impact of a computerized system to report late-arriving laboratory results in the emergency department.

BACKGROUND: Results of some laboratory tests for Emergency Department (ED) patients return hours to days after the patient is discharged. Inadequate follow-up for these late-arriving results poses medical and legal risks. We have developed, but not yet implemented, a computerized system called the Automated Late-Arriving Results Monitoring System (ALARMS). ALARMS scans the hospital's laboratory and ED registration databases to generate an electronic daily log of all late-arriving abnormal laboratory results for ED patients. OBJECTIVE: To determine the potential impact of ALARMS by assessing our ED's current quality of documented follow-up of late-arriving laboratory results. METHODS: We applied ALARMS retrospectively, to find all abnormal late-arriving laboratory results returned between 5/1/96 and 4/30/98 for ED patients for the following three tests: serum lead levels, Chlamydia cultures, or urine pregnancy tests. Medical records were reviewed for documentation of follow-up, which was considered appropriate if a clinician noted the abnormal result and documented a follow-up plan within 1 week after the result became available. Medical records were also reviewed for any evidence of complications attributable to delayed or inadequate follow-up. RESULTS: Over the 2-year study period, no appropriate follow-up was documented in 6/18 (33%) cases of elevated lead levels, 3/4 (75%) cases of late-arriving positive pregnancy tests, and 23/39 (59%) cases of positive Chlamydia cultures. One case of a positive Chlamydia culture, for which there was no documented follow-up, was associated with subsequent development of pelvic inflammatory disease. CONCLUSION: Our current system of documented follow-up for late-arriving laboratory results has deficiencies. ALARMS, a computerized system of alerts for emergency physicians, has the potential to substantially improve documented follow-up of late-arriving laboratory results in the ED.

Antibiotic treatment of children with unsuspected meningococcal disease.

BACKGROUND: Data from an earlier study suggest that patients with unsuspected meningococcal disease (UMD) cannot be differentiated easily from febrile children with viral syndromes on the basis of physical examinations or peripheral blood counts. Some children with meningococcal disease therefore are treated inadvertently as outpatients. OBJECTIVE: To determine whether antibiotic therapy administered at the outpatient visit prevents complications, permanent sequelae, or death in children with UMD. METHODS: We reviewed the medical records of patients younger than 20 years with invasive meningococcal disease at 7 pediatric referral centers from January 1, 1981, through December 31, 1996. Patients were considered to have UMD if they underwent evaluation and discharge as outpatients and if blood and/or cerebrospinal fluid cultures obtained at evaluation yielded Neisseria meningitidis. We compared the frequency of development of complications (meningitis, sepsis, and pericarditis), permanent sequelae (limb amputation, skin grafting, and persistent neurologic disability) or death between patients who did and did not receive antibiotics at the outpatient visits. RESULTS: Of 58 children with UMD, 19 (33%) received antibiotics and 39 (67%) did not. Complications occurred significantly less frequently in the antibiotic-treated group (7/19 [37%] vs 27/39 [69%]; odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.81; P = .03). There was no significant difference in death or permanent sequelae between groups (0/19 vs 3/39 [8%]; OR, 0; 95% CI, 0-2.61; P=.54). There was insufficient power, however, to exclude the possibility of a clinically meaningful difference between the groups with regard to these latter outcomes. CONCLUSIONS: Antibiotic administration to young patients with UMD at the time of the outpatient visit is associated with a reduction in complications from this disease. Although the routine use of antibiotics in febrile outpatients younger than 20 years cannot be advocated, empirical treatment should be considered in the setting of higher probability of meningococcal disease.

Parents as direct contributors to the medical record: validation of their electronic input.

STUDY OBJECTIVES: We assessed the validity and completeness of data in the past medical history (PMH) obtained electronically from parents and examined effects of the human-computer interface and sociodemographic variables on electronic parental report. METHODS: We compared parents' electronic report of PMH data with a criterion standard, structured face-to-face interview by a pediatrician blinded to the electronic data. The electronic medical record interface enabled parents to provide 5 elements of the PMH: birth status, allergies, current medications, immunization status, and previous hospitalizations. The setting was the emergency department waiting room in an academic, urban children's hospital; parents of infants up to 12 months old participated. Outcome measures were validity of the PMH data obtained using the electronic medical record interface and odds of having an invalid or incomplete response using the electronic medical record interface. RESULTS: One hundred parents were enrolled (69.4% of eligible subjects). Study subjects did not differ from nonenrollees on demographic variables and visit characteristics. The validity of the electronic medical record interface data was high across the PMH elements (94% to 99%). Two demographic features predicted invalid response: parental primary language other than English or Spanish (odds ratio [OR] 11.4, 95% confidence interval CI 1.7 to 76.3), and Asian ethnicity (OR 14. 6, 95% CI 1.2 to 182.4). Incomplete responses were predicted by limited previous experience with computers; computer-naive subjects had an eightfold increased odds of skipping a question (OR 7.9, 95% CI 1.8 to 34.6). CONCLUSION: Parents are accurate independent reporters of their infants' general PMH using the electronic medical record interface. Their participation in care may be enhanced by allowing them to contribute medical information directly to the electronic medical record.

Insertion of long lines in the pediatric emergency department.

OBJECTIVE: The purpose of this study was: 1) to evaluate the role of the pediatric emergency department (PED) in placing peripherally inserted midline or central catheters (long lines), and 2) to review indications and complications to use this technology to reduce the number and duration of admissions and provide an alternative method for administering intravenous therapy. METHODS: Retrospective chart review of all patients taken from a procedure log who had long lines placed in the emergency department of a children's hospital. RESULTS: Twenty-eight patients had 30 long line insertions over a 36-month period. Fourteen were female; age ranged from 1 to 36 years with a median of 9 and a mean of 11.1 +/- 8.4. The indication for insertion was for parenteral antibiotics in 27 of 28 (96%) patients and for parenteral nutrition in 1 (4%) patient. The catheters varied in length from 8 to 60 cm. Twelve of 30 (40%) catheters terminated centrally in the subclavian or superior vena cava, while 18 (60%) were in the peripheral cephalic, basilic, or axillary veins. Chest radiography confirmed positioning in 12 of 12 inserted centrally and in 15 of 18 (83%) in the peripheral circulation. Half of the patients received no premedication for the procedure; 10 (33%) received topical anesthetic cream; 2 (7%) local infiltration of anesthetic, and 2 (7%) parenteral sedation. Twenty-one of 30 (70%) patients were discharged directly from the emergency department; 3 (10%) were discharged after admission to the hospital to complete treatment at home with their long lines, and 6 (20%) used their long lines for in-hospital therapy only. Eight of 30 (27%) placements were for patients specifically referred to the PED for placement or replacement of a long line. Twelve of 30 (40%) lines were placed in children presenting for intravenous therapy for cellulitis. These patients received a long line with home i.v. therapy instead of the traditional admission. The duration of intravenous treatment documented for all patients ranged from 1 to 62 days with a median of 10.5, and a mean of 16.2 +/- 17.8, compared with the duration of the line ranging from 1 to 28 days with a median of 4, and a mean of 7.3 +/- 8.0. Ten of 30 (33%) had their line for 3 days or less. The short duration was due to problems with line function in 5 of 10, and intentional removal secondary to improved cellulitis in 5. There were no significant complications with the lines reported during placement or while in use; however, 8 of 30 (27%) of the lines placed developed problems with function, requiring repair or replacement. CONCLUSIONS: 1) Long lines can be inserted in the pediatric emergency department by physicians with different levels of training with minor complications and no adverse clinical effects; 2) the placement of long lines can eliminate the need for hospitalization in some cases, reduce the duration of hospitalization in others, and lessen the need for repeated venipunctures for routine peripheral catheter replacement in patients requiring i.v. therapy; 3) the planned duration of therapy as well as other factors not analyzed in this study should be considered when selecting patients for long line placement in the emergency department.

The spontaneous passage of esophageal coins in children.

OBJECTIVES: To determine the likelihood of spontaneous passage of esophageal coins to the stomach in children and to determine the effect of initial coin location on spontaneous passage. DESIGN: Retrospective review of medical records and radiographs. SUBJECTS: Consecutive patients 18 years or younger presenting during a 24-month period (October 1995 to September 1997) whose evaluation revealed an esophageal coin. SETTING: The emergency department of a large, urban academic children's hospital. MAIN OUTCOME MEASURES: Independent measures were time between ingestion and radiographs, initial location of the coin, and categorization of case as "simple" (patients without a history of esophageal disease or surgery, with a single esophageal coin lodged less than 24 hours, and with no respiratory compromise on presentation) or "complex." Dependent measures were spontaneous passage of the coin to the stomach and the time to passage. RESULTS: A total of 116 cases were included in the analysis, of which 84 were simple and 32 complex. Among the 84 simple cases, the coin was initially located in the proximal third of the esophagus in 54 (64%), the middle third in 7 (8%), and the distal third in 22 (26%). For the 32 complex cases, the initial location of the coin was the proximal third of the esophagus in 27 (84%) and the middle third in 5 (16%). Subsequent radiographs were obtained in the emergency department in 58 (69%) of the simple cases. Among these cases, spontaneous passage of the coin to the stomach occurred in 16 (28% [95% confidence interval, 21%-41%]). By initial coin location, spontaneous passage in this group occurred in 22% (7/32) of proximal, 33% (2/6) of middle, and 37% (7/19) of distal esophageal coins (P >.05). Subsequent radiographs were obtained in 14 (44%) of the complex cases; no coin had passed spontaneously to the stomach in these patients (0% [95% confidence interval, 0%-20%]). CONCLUSIONS: Children with a single esophageal coin seen within 24 hours of ingestion, who have no history of esophageal disease and no respiratory compromise on presentation, have a 28% chance of spontaneous passage of the coin to the stomach. Coins in the upper as well as the lower esophagus pass spontaneously. Observing these children for 12 to 24 hours prior to invasive procedures will reduce complications and costs.

Ultrasonography and limited computed tomography in the diagnosis and management of appendicitis in children.

CONTEXT: Limited computed tomography with rectal contrast (CTRC) has been shown to be 98% accurate in the diagnosis of appendicitis in the adult population, but data are lacking regarding the accuracy and effectiveness of this technique in diagnosing pediatric appendicitis. OBJECTIVE: To determine the diagnostic value of a protocol involving ultrasonography and CTRC in the diagnosis and management of appendicitis in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 139 children and adolescents aged 3 to 21 years (2 patients were older than 18 years) who had equivocal clinical findings for acute appendicitis and who presented to the emergency department of a large, urban, pediatric teaching hospital between July and December 1998. Interventions Children were first evaluated with pelvic ultrasonography. If the result was definitive for appendicitis, laparotomy was performed; if ultrasonography was negative or inconclusive, CTRC was obtained. Patients who did not undergo laparotomy had telephone follow-up at 2 weeks and medical records of all patients were reviewed 4 to 6 months after study completion. MAIN OUTCOME MEASURES: Specificity, sensitivity, positive predictive value, negative predictive value, and accuracy of tests based on final diagnoses; surgeons' estimated likelihood of appendicitis on a scale of 1 to 10 for each case and their case management plans before imaging, after ultrasonography, and after CTRC. RESULTS: A total of 108 patients underwent both ultrasonography and CTRC examinations. The protocol had a sensitivity of 94%, specificity of 94%, positive predictive value of 90%, negative predictive value of 97%, and accuracy of 94%. A normal appendix was identified by ultrasonography in 2 (2.4%) of 83 patients without appendicitis and by CTRC in 62 (84%) of 74 patients. A negative ultrasonography result did not change the surgeons' clinical confidence level in excluding appendicitis (P= .06), while a negative CTRC result did have a significant effect (P<.001). Positive results obtained for either ultrasonography or CTRC significantly affected surgeons' estimated likelihood of appendicitis (P=.001 and P<.001, respectively). Ultrasonography resulted in a beneficial change in patient management in 26 (18.7%) of 139 children while CTRC correctly changed management in 79 (73.1%) of 108. CONCLUSIONS: These data show that CTRC following a negative or indeterminate ultrasonography result is highly accurate in the diagnosis of appendicitis in children.

Clinical and hematologic features do not reliably identify children with unsuspected meningococcal disease.

OBJECTIVE: To determine the frequency of unsuspected meningococcal disease (UMD) in young febrile children with meningococcal infections and evaluate whether clinical and laboratory parameters commonly used in the evaluation of fever can help identify children with UMD. METHODS: We reviewed the records of children with meningococcal disease from 1985 to 1996 at four referral centers. Children who were evaluated as outpatients and then discharged to home, from whom Neisseria meningitidis was isolated from blood or cerebrospinal fluid cultures obtained during these outpatient visits, were considered to have UMD. We compared clinical and laboratory parameters between these children and 6414 febrile outpatients 3 to 36 months old with negative blood cultures enrolled in a separate study of occult bacteremia. RESULTS: We identified 381 children with meningococcal disease, of whom 45 (12%) had UMD. Of the 45 with UMD, 37 (82%) were 3 to 36 months old. Compared with the 6414 culture-negative patients, these 37 patients with UMD were significantly younger (8.9 +/- 5.4 vs 14.2 +/- 8.1 months) and had significantly higher band counts (14.3 +/- 11.1 vs 7.3 +/- 7.5%). There were no significant differences, however, in temperature, white blood cell counts, and absolute neutrophil counts. Multivariate analysis identified young age and the band count as independent predictors of UMD. CONCLUSIONS: Children ultimately diagnosed with meningococcal disease have commonly been evaluated as outpatients and discharged to home before diagnosis. Of the hematologic parameters frequently used in the evaluation of fever, only the band count differs significantly between young febrile children with UMD and those with negative cultures. Because UMD is uncommon in young febrile pediatric outpatients, however, the predictive value of the band count is low. Thus, the complete blood count is not routinely helpful for the diagnosis of UMD.

Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide.

Septic shock induced by lipopolysaccharide (LPS) triggering of cytokine production from monocytes/macrophages is a major cause of morbidity and mortality. The major monocyte/macrophage LPS receptor is the glycosylphosphatidylinositol (GPI)-anchored glycoprotein CD14. Here we demonstrate that CD14 coimmunoprecipitates with Gi/Go heterotrimeric G proteins. Furthermore, we demonstrate that heterotrimeric G proteins specifically regulate CD14-mediated, LPS-induced mitogen-activated protein kinase (MAPK) activation and cytokine production in normal human monocytes and cultured cells. We report here that a G protein binding peptide protects rats from LPS-induced mortality, suggesting a functional linkage between a GPI-anchored receptor and the intracellular signaling molecules with which it is physically associated.

Occult bacteremia with group B streptococci in an outpatient setting.

OBJECTIVES: We undertook this study to determine the relative frequency of occult bacteremia with group B streptococci (GBS) and to define the clinical features of infants with occult bacteremia attributable to GBS at the time of initial clinical contact. DESIGN: The logs of the microbiology laboratory were reviewed for blood and cerebrospinal fluid isolates of GBS from 1982 to 1996. Records of patients identified with GBS were abstracted. Patients were classified as having occult bacteremia if GBS were isolated from their blood and they seemed nontoxic and had no apparent clinical or laboratory evidence of focal infection. All other patients were diagnosed with sepsis, meningitis, or nonmeningeal foci. RESULTS: We reviewed the medical records of 147 children with GBS and identified 108 outpatients, including 47 (44%) with occult bacteremia, 42 (39%) with meningitis, 11 (10%) with nonmeningeal foci, and 8 (7%) with sepsis. Compared with patients with sepsis or focal infections, those with occult bacteremia were older (61.1 vs 39.1 days) and had slightly, although not significantly, higher white blood cell (WBC) counts (13 280 +/- 6854 vs 10 688 +/- 8574), but similar degrees of fever. Among the 47 patients with occult bacteremia, none died, as compared with 2 of 61 with serious infections, and fewer had neurologic sequelae (0/47 vs 11/61). Patients with occult bacteremia >90 days of age generally had temperatures >39 degreesC (9/11, mean 39.3 degreesC) and WBC counts >15 000/mm3 (7/10, mean 19 070/mm3), both of which differed significantly compared with those who were <90 days of age. Thirty of the 47 patients with occult bacteremia received intravenous antibiotics and recovered. One of 8 patients discharged without antibiotics and none of 8 with antibiotics developed a focal complication; 1 discharged patient was lost to follow-up. CONCLUSIONS: Almost one-half of the children with GBS disease beyond the immediate neonatal period had occult bacteremia. Among 8 untreated patients with bacteremia, 1 developed a focal complication. Although the small proportion of children with GBS occult bacteremia who were >90 days of age usually had the risk factors of temperature >39 degrees C and WBC >15 000/mm3, as seen with occult bacteremia attributable to other organisms, the majority of the patients who were younger did not have a characteristic clinical syndrome. Prevention of sequelae in these young infants will require a low threshold for diagnosis and treatment.

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 degrees 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/mm3 increase, 95% confidence interval [CI] 1.06, 1.25), temperature (adjusted OR 1.77 for each 1 degree 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 cell/mm3 had OPB (95% CI 6.3, 10.1%) versus .8% of patients with ANCs less than 10,000 cells/mm3 (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 degrees 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.

Incidence of bacteremia in infants and children with fever and petechiae.

OBJECTIVE: We determined the incidence of serious invasive bacteremia caused by Neisseria meningitidis and other organisms in febrile infants and children with a petechial rash. Further, we studied the diagnostic value of laboratory and clinical finding in these patients. STUDY DESIGN: We conducted this prospective cohort study in the emergency department of an urban pediatric teaching hospital, during an 18-month period, and enrolled consecutive patients with temperature of 38 degrees C or higher and petechiae. Our measures included (1) laboratory tests (leukocyte count, coagulation profile, blood culture, and cerebrospinal fluid bacterial culture); (2) a questionnaire requesting clinical data including general appearance, number and location of petechiae, and presence or absence of purpura; and (3) a follow-up telephone survey documenting health status. RESULTS: A total of 411 patients were enrolled, with 57.7% between 3 and 36 months of age. Eight patients (1.9%) had bacteremia or clinical sepsis. Six had serious invasive bacteremia: N. meningitidis (two patients), group A streptococcus (one), or sepsis with negative culture results (three). Two had occult bacteremia caused by Streptococcus pneumoniae and no evidence of sepsis. No patient had a positive cerebrospinal fluid culture result. None of the 357 well-appearing patients (95% confidence interval: 0.0%, 1.0%) had serious invasive bacteremia. Fifty-three patients appeared ill, including all six with serious invasive bacteremia. Ill appearance of the child had a sensitivity of 1.00 (95% confidence interval: 0.60, 1.00), and a leukocyte count of 15,000 or greater, or of less than 5000, had a sensitivity of 1.0 (95% confidence interval: 0.53, 1.00) for detecting serious invasive bacteremia. All children with meningococcemia had purpura. CONCLUSIONS: Invasive bacteremia occurred less frequently in our study than in previous series and was identified by clinical criteria. Our data support the treatment of selected well-appearing children with fever and petechiae as outpatients.

Development of a model of low-inoculum Streptococcus pneumoniae intrapulmonary infection in infant rats.

We have developed a model of low-inoculum Streptococcus pneumoniae infection in infant rats. We challenged 4-day-old Sprague-Dawley pups via intraperitoneal or intrapulmonary injection of S. pneumoniae serotypes 1, 3, 4, 5, 6b, 7f, 9v, 14, 19f, and 23f. To achieve bacteremia with low inocula, it was necessary to passage the isolates in rats. Inocula of the 10 S. pneumoniae serotypes producing bacteremia in 50% or more animals ranged from 1 to 400 CFU. Virulence was similar by intraperitoneal and intrapulmonary routes. Lung specimens from animals challenged by the intrapulmonary route grew S. pneumoniae and demonstrated histologic evidence of focal infection. Meningitis was detected in 20 to 50% of bacteremic animals, and mortality invariably followed bacteremia within 24 to 48 h. This model of intrapulmonary infection uses low inocula of S. pneumoniae and results in bacteremia, meningitis, and death in infant rats.

Duration of fever and its relationship to bacteremia in febrile outpatients three to 36 months old. The Occult Bacteremia Study Group.

OBJECTIVE: To determine the relationship between the duration of fever as reported by caregivers and the likelihood of occult bacteremia in highly febrile young children. METHODS: This is a prospective cohort study performed as part of a prior, multicenter, randomized, interventional trial of oral versus intramuscular antibiotics in the prevention of complications of occult bacteremia in febrile children presenting to nine urban pediatric emergency departments at eight medical centers. Participants included children three to 36 months of age with a temperature of > or = 39.0 degrees C and a nonfocal illness (or uncomplicated otitis media) managed as outpatients. The outcome measure was the presence of bacteremia. RESULTS: Of the 6680 randomized patients, 6619 (99.1%) had a culture of their blood and a valid reported duration of fever. The median duration of fever in patients with bacteremia (n = 192) and without bacteremia (n = 6427) was the same, one to two days, but the mean rank of patients with bacteremia was significantly lower than that of patients without bacteremia (P + 0.0009). A significantly greater proportion of patients with fever < 1 day had bacteremia than patients with fever > or = 1 day (P = 0.004), and a significantly greater proportion of patients with fever < 2 days had bacteremia than patients with fever > or = 2 days (P = 0.009). The sensitivity, specificity, positive predictive value, and negative predictive value of fever < 1 day in detecting occult bacteremia were 40.1, 69.8, 3.8, and 97.5%, respectively.