Diana H. Kearney

Oral Versus Initial Intravenous Therapy for Urinary Tract Infections in Young Febrile Children

Background. The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy. Methods. In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days. Results. Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was ∼8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously (

Treatment of Acute Otitis Media in Children under 2 Years of Age

3577 vs

Factors That Influence Parental Decisions to Participate in Clinical Research: Consenters vs Nonconsenters

1473) compared with those treated orally. Conclusions. Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.

Risk Factors for Recurrent Urinary Tract Infection and Renal Scarring

BACKGROUND Recommendations vary regarding immediate antimicrobial treatment versus watchful waiting for children younger than 2 years of age with acute otitis media. METHODS We randomly assigned 291 children 6 to 23 months of age, with acute otitis media diagnosed with the use of stringent criteria, to receive amoxicillin-clavulanate or placebo for 10 days. We measured symptomatic response and rates of clinical failure. RESULTS Among the children who received amoxicillin-clavulanate, 35% had initial resolution of symptoms by day 2, 61% by day 4, and 80% by day 7; among children who received placebo, 28% had initial resolution of symptoms by day 2, 54% by day 4, and 74% by day 7 (P=0.14 for the overall comparison). For sustained resolution of symptoms, the corresponding values were 20%, 41%, and 67% with amoxicillin-clavulanate, as compared with 14%, 36%, and 53% with placebo (P=0.04 for the overall comparison). Mean symptom scores over the first 7 days were lower for the children treated with amoxicillin-clavulanate than for those who received placebo (P=0.02). The rate of clinical failure--defined as the persistence of signs of acute infection on otoscopic examination--was also lower among the children treated with amoxicillin-clavulanate than among those who received placebo: 4% versus 23% at or before the visit on day 4 or 5 (P<0.001) and 16% versus 51% at or before the visit on day 10 to 12 (P<0.001). Mastoiditis developed in one child who received placebo. Diarrhea and diaper-area dermatitis were more common among children who received amoxicillin-clavulanate. There were no significant changes in either group in the rates of nasopharyngeal colonization with nonsusceptible Streptococcus pneumoniae. CONCLUSIONS Among children 6 to 23 months of age with acute otitis media, treatment with amoxicillin-clavulanate for 10 days tended to reduce the time to resolution of symptoms and reduced the overall symptom burden and the rate of persistent signs of acute infection on otoscopic examination. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00377260.).

Validation of a decision rule identifying febrile young girls at high risk for urinary tract infection.

IMPORTANCE A childs health, positive perceptions of the research team and consent process, and altruistic motives play significant roles in the decision-making process for parents who consent for their child to enroll in clinical research. This study identified that nonconsenting parents were better educated, had private insurance, showed lower levels of altruism, and less understanding of study design. OBJECTIVE To determine the factors associated with parental consent for their childs participation in a randomized, placebo-controlled trial. DESIGN Cross-sectional survey conducted from July 2008 to May 2011. The survey was an ancillary study to the Randomized Intervention for Children with VesicoUreteral Reflux Study. SETTING Seven childrens hospitals participating in a randomized trial evaluating management of children with vesicoureteral reflux. PARTICIPANTS Parents asked to provide consent for their childs participation in the randomized trial were invited to complete an anonymous online survey about factors influencing their decision. A total of 120 of the 271 (44%) invited completed the survey; 58 of 125 (46%) who had provided consent and 62 of 144 (43%) who had declined consent completed the survey. MAIN OUTCOMES AND MEASURES A 60-question survey examining child, parent, and study characteristics; parental perception of the study; understanding of the design; external influences; and decision-making process. RESULTS Having graduated from college and private health insurance were associated with a lower likelihood of providing consent. Parents who perceived the trial as having a low degree of risk, resulting in greater benefit to their child and other children, causing little interference with standard care, or exhibiting potential for enhanced care, or who perceived the researcher as professional were significantly more likely to consent to participate. Higher levels of understanding of the randomization process, blinding, and right to withdraw were significantly positively associated with consent to participate. CONCLUSIONS AND RELEVANCE Parents who declined consent had a relatively higher socioeconomic status, had more anxiety about their decision, and found it harder to make their decision compared with consenting parents, who had higher levels of trust and altruism, perceived the potential for enhanced care, reflected better understanding of randomization, and exhibited low decisional uncertainty. Consideration of the factors included in the conceptual model should enhance the quality of the informed consent process and improve participation in pediatric clinical trials.

Development and preliminary evaluation of a parent-reported outcome instrument for clinical trials in acute otitis media.

OBJECTIVES: To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis. METHODS: This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring. RESULTS: Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09–3.93]) and presence of renal scarring on the baseline 99mTc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22–6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86–4.87]). CONCLUSIONS: VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.

Responsiveness and construct validity of a symptom scale for acute otitis media.

Objective: To validate a previously published clinical decision rule to predict risk of urinary tract infection in febrile young girls. Methods: We performed a retrospective case‐control study at a childrens hospital emergency department in a different city than that in which the original derivation study took place. Girls younger than 2 years in whom urinalysis and urine culture were performed for evaluation of fever were eligible. Cases consisted of all patients with a positive urine culture result, defined as 50,000 or more colony‐forming units per milliliter of a urinary tract pathogen (n = 98). A random sample of patients with a negative urine culture result (n = 114) was also selected as controls. The clinical prediction rule included five risk factors: age younger than 12 months, white race, temperature of 39.0°C or higher, absence of any other potential source of fever, and fever for 2 days or more. The sensitivity and false‐positive rate of this rule were calculated at different cutoff values. Results: The overall discriminative ability of the rule, as indicated by the area under the receiver‐operator characteristic curve (AUC), was similar in this validation sample (AUC = 0.72) to that in the original study (AUC = 0.76). However, in the validation sample, the presence of three or more risk factors (rather than two or more as in the original study) appeared to be the optimum cutoff to define a positive rule, which results in an indication for obtaining further diagnostic testing (sensitivity, 88% [95% CI, 79–94%]; false‐positive rate, 70% [95% CI, 61–79%]). Conclusion: A simple clinical decision rule previously developed to predict urinary tract infection based on five risk factors performs similarly in a different patient population.

Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children

Background: Acute otitis media (AOM) is the most common childhood diagnosis, leading to prescription of an antibiotic in the United States. Although antibiotics are used in children with AOM, in part, to shorten the duration of symptoms, no instruments have been developed to track early changes in symptoms from the parents point of view. The goal of the present study was to develop and evaluate a parent-reported symptom scale for children with AOM (AOM-SOS) for use as an outcome measure in AOM treatment trials. Methods: From a pool of 28 potential symptoms, we selected 7 on the basis of parent questionnaire, expert interviews, and review of the literature for inclusion in the AOM-SOS. We administered the AOM-SOS to a primary-care sample of children aged 6–25 months enrolled in a study of nasopharyngeal bacterial colonization. Children were seen for well visits, illness visits, and AOM follow-up visits. At each visit, parents completed the AOM-SOS and their children were examined by trained otoscopists. As part of the evaluation of the AOM-SOS, we examined the association between each item on the questionnaire and the clinical diagnosis of AOM while adjusting for the presence of upper respiratory tract infection. To assess responsiveness, we examined the change in AOM-SOS scores in patients with AOM who were seen for follow-up within 3 weeks of diagnosis. Results: We evaluated 264 children (mean age, 12.5 months at entry) at a total of 642 visits. We diagnosed AOM at 24% of the visits. Each item on the questionnaire was significantly associated with the clinical diagnosis of AOM (P < 0.001 for each), before and after adjusting for the presence or absence of upper respiratory infection. The mean AOM-SOS score at visits when AOM was diagnosed was 3.71, compared with 0.96 at visits when AOM was not diagnosed (P < 0.001). Internal reliability of the scale as measured by Cronbachs &agr; was 0.84. AOM-SOS scores in children with AOM who were otoscopically improved decreased by an average of 2.81 points (standardized response mean = 0.73). Conclusions: We have developed a short symptom scale for children with AOM. This study provides preliminary data on the performance of the AOM-SOS in a primary care sample of children.

Penicillin susceptibility of pneumococcal isolates causing acute otitis media in children: Seasonal variation

Background: Because resolution of symptoms is a primary goal of antimicrobial therapy in children with acute otitis media (AOM), measurement of symptoms in studies of antimicrobial effectiveness in such children is important. We have developed a scale for measuring symptoms of AOM in young children (AOM-SOS), and we present data on its construct validity and responsiveness. Methods: We followed children 3 months to 3 years of age with AOM, who were receiving antimicrobial treatment, using the AOM-SOS scale. The scale was administered at the enrollment visit, as a twice-a-day diary measure, and at the follow-up visit (days 5–7). To evaluate construct validity, we examined the correlation, at entry, between AOM-SOS scores and scores on other measures of pain and functional status. To evaluate the scales responsiveness, we examined the change in scale scores from entry to follow-up. We also examined the levels of agreement between the scale scores and overall assessments of the children by parents. Results: We enrolled 70 children (mean age 12.5 months) of whom 57 returned for follow-up. The magnitude of the correlations between the AOM-SOS scale scores and other measures of pain and functional status ranged from 0.56 to 0.84. The responsiveness of the AOM-SOS, as measured by the standardized response mean was 1.20. Conclusions: These data support the validity and responsiveness of the AOM-SOS; the scale seems to measure effectively both pain and overall functional status in young children with AOM. Changes in score over the first few days of illness were substantial and generally matched the assessments both of parents and of clinicians. The AOM-SOS promises to be useful as an outcome measure in clinical studies of AOM.

Signs and Symptoms that Differentiate Acute Sinusitis from Viral Upper Respiratory Tract Infection

BACKGROUND Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media. METHODS We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms. RESULTS Children who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001). CONCLUSIONS Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107 .).