Jonathan E. Bennett

Effect of Antibiotic Pretreatment on Cerebrospinal Fluid Profiles of Children With Bacterial Meningitis

OBJECTIVE. The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis. METHODS. We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture. RESULTS. We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with ≥12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for <12 hours, had significantly higher median cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median cerebrospinal fluid protein levels (121 vs 178 mg/dL). CONCLUSIONS. In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.

Febrile Infants With Urinary Tract Infections at Very Low Risk for Adverse Events and Bacteremia

BACKGROUND: There is limited evidence from which to derive guidelines for the management of febrile infants aged 29 to 60 days with urinary tract infections (UTIs). Most such infants are hospitalized for ≥48 hours. Our objective was to derive clinical prediction models to identify febrile infants with UTIs at very low risk of adverse events and bacteremia in a large sample of patients. METHODS: This study was a 20-center retrospective review of infants aged 29 to 60 days with temperatures of ≥38°C and culture-proven UTIs. We defined UTI by growth of ≥50 000 colony-forming units (CFU)/mL of a single pathogen or ≥10 000 CFU/mL in association with positive urinalyses. We defined adverse events as death, shock, bacterial meningitis, ICU admission need for ventilator support, or other substantial complications. We performed binary recursive partitioning analyses to derive prediction models. RESULTS: We analyzed 1895 patients. Adverse events occurred in 51 of 1842 (2.8% [95% confidence interval (CI): 2.1%–3.6%)] and bacteremia in 123 of 1877 (6.5% [95% CI: 5.5%–7.7%]). Patients were at very low risk for adverse events if not clinically ill on emergency department (ED) examination and did not have a high-risk past medical history (prediction model sensitivity: 98.0% [95% CI: 88.2%–99.9%]). Patients were at lower risk for bacteremia if they were not clinically ill on ED examination, did not have a high-risk past medical history, had a peripheral band count of <1250 cells per μL, and had a peripheral absolute neutrophil count of ≥1500 cells per μL (sensitivity 77.2% [95% CI: 68.6%–84.1%]). CONCLUSION: Brief hospitalization or outpatient management with close follow-up may be considered for infants with UTIs at very low risk of adverse events.

Performance of Ultrasound in the Diagnosis of Appendicitis in Children in a Multicenter Cohort

OBJECTIVES The objectives were to assess the test characteristics of ultrasound (US) in diagnosing appendicitis in children and to evaluate site-related variations based on the frequency of its use. Additionally, the authors assessed the test characteristics of US when the appendix was clearly visualized. METHODS This was a secondary analysis of a prospective, 10-center observational study. Children aged 3 to 18 years with acute abdominal pain concerning for appendicitis were enrolled. US was performed at the discretion of the treating physician. RESULTS Of 2,625 patients enrolled, 965 (36.8%) underwent abdominal US. US had an overall sensitivity of 72.5% (95% confidence interval [CI] = 58.8% to 86.3%) and specificity 97.0% (95% CI = 96.2% to 97.9%) in diagnosing appendicitis. US sensitivity was 77.7% at the three sites (combined) that used it in 90% of cases, 51.6% at a site that used it in 50% of cases, and 35% at the four remaining sites (combined) that used it in 9% of cases. US retained a high specificity of 96% to 99% at all sites. Of the 469 (48.6%) cases across sites where the appendix was clearly visualized on US, its sensitivity was 97.9% (95% CI = 95.2% to 99.9%), with a specificity of 91.7% (95% CI = 86.7% to 96.7%). CONCLUSIONS Ultrasound sensitivity and the rate of visualization of the appendix on US varied across sites and appeared to improve with more frequent use. US had universally high sensitivity and specificity when the appendix was clearly identified. Other diagnostic modalities should be considered when the appendix is not definitively visualized by US.

The effect of abdominal pain duration on the accuracy of diagnostic imaging for pediatric appendicitis.

STUDY OBJECTIVE Advanced imaging with computed tomography (CT) or ultrasonography is frequently used to evaluate for appendicitis. The duration of the abdominal pain may be related to the stage of disease and therefore the interpretability of radiologic studies. Here, we investigate the influence of the duration of pain on the diagnostic accuracy of advanced imaging in children being evaluated for acute appendicitis. METHODS A secondary analysis of a prospective multicenter observational cohort of children aged 3 to 18 years with suspected appendicitis who underwent CT or ultrasonography was studied. Outcome was based on histopathology or telephone follow-up. Treating physicians recorded the duration of pain. Imaging was coded as positive, negative, or equivocal according to an attending radiologists interpretation. RESULTS A total of 1,810 children were analyzed (49% boys, mean age 10.9 years [SD 3.8 years]); 1,216 (68%) were assessed by CT and 832 (46%) by ultrasonography (238 [13%] had both). The sensitivity of ultrasonography increased linearly with increasing pain duration (test for trend: odds ratio=1.39; 95% confidence interval 1.14 to 1.71). There was no association between the sensitivity of CT or specificity of either modality with pain duration. The proportion of equivocal CT readings significantly decreased with increasing pain duration (test for trend: odds ratio=0.76; 95% confidence interval 0.65 to 0.90). CONCLUSION The sensitivity of ultrasonography for appendicitis improves with a longer duration of abdominal pain, whereas CT demonstrated high sensitivity regardless of pain duration. Additionally, CT results (but not ultrasonographic results) were less likely to be equivocal with longer duration of abdominal pain.

Interrater Reliability of Clinical Findings in Children With Possible Appendicitis

OBJECTIVE: Our objective was to determine the interrater reliability of clinical history and physical examination findings in children undergoing evaluation for possible appendicitis in a large, multicenter cohort. METHODS: We conducted a prospective, multicenter, cross-sectional study of children aged 3–18 years with possible appendicitis. Two clinicians independently evaluated patients and completed structured case report forms within 60 minutes of each other and without knowing the results of diagnostic imaging. We calculated raw agreement and assessed reliability by using the unweighted Cohen κ statistic with 2-sided 95% confidence intervals. RESULTS: A total of 811 patients had 2 assessments completed, and 599 (74%) had 2 assessments completed within 60 minutes. Seventy-five percent of paired assessments were completed by pediatric emergency physicians. Raw agreement ranged from 64.9% to 92.3% for history variables and 4 of 6 variables had moderate interrater reliability (κ > .4). The highest κ values were noted for duration of pain (κ = .56 [95% confidence intervals .51–.61]) and history of emesis (.84 [.80–.89]). For physical examination variables, raw agreement ranged from 60.9% to 98.7%, with 4 of 8 variables exhibiting moderate reliability. Among physical examination variables, the highest κ values were noted for abdominal pain with walking, jumping, or coughing (.54 [.45–.63]) and presence of any abdominal tenderness on examination (.49 [.19–.80]). CONCLUSIONS: Interrater reliability of patient history and physical examination variables was generally fair to moderate. Those variables with higher interrater reliability are more appropriate for inclusion in clinical prediction rules in children with possible appendicitis.

Predicting pertussis in infants.

Background: The incidence of reported cases of pertussis is increasing, despite high rates of vaccination among infants and children. The burden of disease, and rates of complication and death are highest among infants. The limited availability of a timely reliable confirmatory test for pertussis hinders early identification of infected infants. Objective: Our objective is to identify clinical and laboratory predictors for pertussis among infants. Methods: Demographic, clinical, and laboratory data were collected from the medical records of all infants aged 12 months or younger who underwent confirmatory testing (culture, direct fluorescent assay, or polymerase chain reaction) for Bordetella pertussis from January 1, 2001, to July 31, 2005. The association of 15 variables with a positive pertussis test was analyzed using univariate and multivariate analysis, and when appropriate, using receiver operating characteristics. Results: We reviewed the medical records of 141 infants who were tested for pertussis. The mean age was 88 days, and the most common chief complaints were cough and breathing difficulty. Eighteen patients (13%) had a positive pertussis test, and 123 (87%) had a negative test. Bronchiolitis and upper respiratory tract infection were the most common discharge diagnoses among infants with a negative test. The 2 groups were similar with respect to sex, history of cough, vomiting, fever, symptoms of apparent life-threatening event, presence of fever, or hypoxia, and heart rate. Infants who were younger (55 days vs 93 days, P = 0.02), evaluated between July and October (23% vs 9%, P = 0.02), less tachypneic (39 breaths/min vs 47 breaths/min, P = 0.02), had higher white blood cell counts (20,000/&mgr;L vs 15000/&mgr;L, P = 0.02), higher percentage of lymphocytes (72 vs 55, P = 0.00), and higher absolute lymphocyte counts ([ALC] 14,536/&mgr;L vs 8357/&mgr;L, P = 0.00) were more likely to have a positive test. Receiver operating characteristics for ALC demonstrated an area under the curve of 0.81, with a 95% confidence interval of 0.72 to 0.90. An ALC cutoff point of 9400 was determined to maximize sensitivity (89%) and specificity (75%). The negative predictive value of this cutoff point was 97%, and the positive likelihood ratio was 3.6, with a 95% confidence interval of 2.3 to 5.4. Conclusions: Among infants who underwent confirmatory testing for pertussis, those who are younger, evaluated between July and October, less tachypneic, have higher white blood cell counts, higher percentage of lymphocytes, and higher ALCs are more likely to have a positive test. The ALC was the best predictor of pertussis, and an ALC of less than 9400/&mgr;L excluded almost all infants without pertussis.

Sterile cerebrospinal fluid pleocytosis in young febrile infants with urinary tract infections.

OBJECTIVES To determine the prevalence of and to identify risk factors for sterile cerebrospinal fluid (CSF) pleocytosis in a large sample of febrile young infants with urinary tract infections (UTIs) and to describe the clinical courses of those patients. DESIGN Secondary analysis of a multicenter retrospective review. SETTING Emergency departments of 20 North American hospitals. Patients Infants aged 29 to 60 days with temperatures of 38.0°C or higher and culture-proven UTIs who underwent a nontraumatic lumbar puncture from January 1, 1995, through May 31, 2006. MAIN EXPOSURE Febrile UTI. OUTCOME MEASURES Presence of sterile CSF pleocytosis defined as CSF white blood cell count of 10/μL or higher in the absence of bacterial meningitis and clinical course and treatment (ie, presence of adverse events, time to defervescence, duration of parenteral antibiotic treatment, and length of hospitalization). RESULTS A total of 214 of 1190 infants had sterile CSF pleocytosis (18.0%; 95% confidence interval, 15.9%-20.3%). Only the peripheral white blood cell count was independently associated with sterile CSF pleocytosis, and patients with a peripheral white blood cell count of 15/μL or higher had twice the odds of having sterile CSF pleocytosis (odds ratio, 1.97; 95% confidence interval, 1.32-2.94; P = .001). In the subset of patients at very low risk for adverse events (ie, not clinically ill in the emergency department and without a high-risk medical history), patients with and without sterile CSF pleocytosis had similar clinical courses; however, patients with CSF pleocytosis had longer parenteral antibiotics courses (median length, 4 days [interquartile range, 3-6 days] vs 3 days [interquartile range, 3-5 days]) (P = .04). CONCLUSION Sterile CSF pleocytosis occurs in 18% of young infants with UTIs. Patients with CSF pleocytosis at very low risk for adverse events may not require longer treatment with antibiotics.

Interobserver Agreement in the Assessment of Clinical Findings in Children With First Unprovoked Seizures

OBJECTIVES: Variables used in prediction rules and clinical guidelines should show acceptable agreement when assessed by different observers. Our objective was to determine the interobserver agreement of patient history and physical examination variables used to assess children undergoing emergency department (ED) evaluation for a first seizure not provoked by a known precipitant such as fever or trauma (ie, an unprovoked seizure). METHODS: We conducted a prospective cohort study of children aged 28 days to 18 years evaluated for unprovoked seizures at 6 tertiary care EDs. We excluded patients if previously evaluated for a similar event. Two clinicians independently completed a clinical assessment before neuroimaging. We determined agreement for each clinical variable by using the unweighted κ statistic. RESULTS: A total of 217 paired observations were analyzed; median patient age was 53.5 months, and 38% were younger than 2 years. Agreement beyond chance was at least moderate (κ ≥ 0.41) for 21 of 31 (68%) variables for which κ could be calculated. κ was ≥0.41 for 7 of 11 (64%) general history variables, all 8 seizure-specific history variables (including seizure focality), and 6 of 12 (50%) physical examination variables. Agreement beyond chance was substantial or better (κ ≥ 0.61) for 2 of 11 (18%) general history variables, for 5 of 8 (63%) seizure-specific history variables, and for 2 of 12 (17%) physical examination variables. CONCLUSIONS: For children with first unprovoked seizures evaluated in the ED, clinicians frequently assess findings from seizure-specific history with substantial agreement beyond chance. Those clinical variables that have been associated with the presence of intracranial abnormalities and show reliability between assessors, such as seizure focality and the presence of any focal neurological finding, may be more useful in the ED assessment of children with first unprovoked seizures.

Diagnostic value of immature neutrophils (bands) in the cerebrospinal fluid of children with cerebrospinal fluid pleocytosis

OBJECTIVE. We evaluated the diagnostic utility of the presence and number of cerebrospinal fluid (CSF) bands in distinguishing bacterial from aseptic meningitis among children with CSF pleocytosis. METHODS. We identified retrospectively a cohort of children 29 days to 19 years of age with CSF pleocytosis (≥10 × 106 leukocytes per L) who were treated in the emergency departments of 8 pediatric centers between January 2001 and June 2004 and whose CSF was evaluated for the presence of bands. We performed bivariate and multivariate analyses to determine the ability of CSF bands to distinguish bacterial from aseptic meningitis. RESULTS. Among 1116 children whose CSF was evaluated for the presence of bands, 48 children (4% of study patients) had bacterial meningitis. Bacterial meningitis, compared with aseptic meningitis, was associated with a greater CSF band proportion (0.03 vs 0.01; difference: 0.02; 95% confidence interval: 0.00–0.04) and CSF absolute band count (392 × 106 cells per L vs 3 × 106 cells per L; difference: 389 × 106 cells per L; 95% confidence interval: −77 × 106 cells per L to 855 × 106 cells per L). In addition, 29% of patients with bacterial meningitis, compared with 18% of patients with aseptic meningitis, had any bands detected in the CSF. After adjustment for other factors associated with bacterial meningitis, however, CSF band presence, CSF absolute band count, and CSF band proportion were not independently associated with bacterial meningitis. CONCLUSION. In this multicenter study, neither the presence nor quantity of CSF bands independently predicted bacterial meningitis among children with CSF pleocytosis.

Accuracy of plain radiographs to exclude the diagnosis of intussusception.

Objectives To prospectively determine the test characteristics of the 3-view abdominal radiograph to decrease the likelihood of ileocolic intussusception. Methods We conducted a prospective cross-sectional study of children aged 3 months to 3 years suspected of having intussusception at a children’s hospital emergency department. Clinicians obtained supine, prone, and left lateral decubitus radiographs. We determined the presence or absence of intussusception by air enema, ultrasound, operative report, or clinical follow-up. A masked pediatric radiologist reviewed all radiographs. The criteria evaluated were whether air was visualized in the ascending colon on each view and in the transverse colon on the supine view. Results Nineteen (14.8%) of 128 patients had intussusception. Using air in the ascending colon on all 3 views as the diagnostic criteria, the test characteristics of the 3-view radiograph were sensitivity, 100% (95% confidence interval [CI], 79.1–100); specificity, 17.4% (95% CI, 11.1–26.1); negative predictive value, 100% (95% CI, 79.1–100); and likelihood ratio of a negative test, 0. When 2 or more of 3 views had air in the ascending colon, sensitivity decreased to 89.5% (95% CI, 75.7–100) and specificity improved to 45.0% (95% CI, 35.6–54.3). Air in the transverse colon had moderate sensitivity, 84.2% (95% CI, 67.8–100), but further improved specificity, 63.3% (95% CI, 54.2–72.4). Conclusions The presence of air in the ascending colon on the 3-view abdominal radiograph can decrease the likelihood of or exclude intussusception. When clinical suspicion is low, the presence of specific criterion on a 3-view abdominal radiograph series may obviate the need for further studies.