Alejandro Hoberman

Prevalence of urinary tract infection in febrile infants

Urinary tract infection (UTI), a relatively common cause of fever in infancy, usually consists of pyelonephritis and may cause permanent renal damage. This study assessed (1) the prevalence of UTI in febrile infants (temperature > or = 38.3 degrees C) with differing demographic and clinical characteristics and (2) the usefulness of urinalysis in diagnosing UTI. We diagnosed UTI in 50 (5.3%) of 945 febrile infants if we found > or = 10,000 colony-forming units of a single pathogen per milliliter in a urine specimen obtained by catheterization. Prevalences were similar in (1) infants aged < or = 2 months undergoing examination for sepsis (4.6%), (2) infants aged > 2 months in whom UTI was suspected, usually because no source of fever was apparent (5.9%), and (3) infants with no suspected UTI, most of whom had other illnesses (5.1%). Female and white infants had significantly more UTIs, respectively, than male and black infants. In all, 17% of white female infants with temperature > or = 39 degrees C had UTI, significantly more (p < 0.05) than any other grouping of infants by sex, race, and temperature. Febrile infants with no apparent source of fever were twice as likely to have UTI (7.5%) as those with a possible source of fever such as otitis media (3.5%) (p = 0.02). Only 1 (1.6%) of 62 subjects with an unequivocal source of fever, such as meningitis, had UTI. As indicators of UTI, pyuria and bacteriuria had sensitivities of 54% and 86% and specificities of 96% and 63%, respectively. In infants with fever, clinicians should consider UTI a potential source and consider a urine culture as part of the diagnostic evaluation.

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 (

Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial

3577 vs

Urinary tract infections in young febrile children

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 of Renal Scarring in Children With a First Urinary Tract Infection: A Systematic Review

OBJECTIVES. There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux. METHODS. One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans. RESULTS. The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis. CONCLUSIONS. Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV.

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

UTI is a common and important clinical problem in infants and young children, with a prevalence of 5.3% among febrile infants seen in our Emergency Department. White females with rectal temperature > or = 39 degrees C are at particularly high risk (prevalence, 17%). Several studies have highlighted the limitations of the standard urinalysis for identifying UTI in infants and young children and have recommended performance of both urinalysis and urine culture. Alternative methods such as dipstick urinalysis, although attractive because of ease of performance, are inadequate as a screen for UTI. Hemocytometer WBC counts of an uncentrifuged urine specimen can be performed in an office or hospital-based laboratory with minimal training. Performance of Gram-stained smears, however, is most appropriate for the hospital-based laboratory. In the hospital setting where both tests can readily be performed, the positive predictive value of the combination of pyuria and bacteriuria (85%) allows prompt institution of antimicrobial therapy before culture results are available, whereas the lower positive predictive value of the single finding of either pyuria or bacteriuria (40%) justifies delaying treatment decisions until culture results are available. In the office setting where hemocytometer counts can easily be performed, culturing only specimens with pyuria and those of children presumptively treated with antimicrobials will result in the identification of almost all patients with true UTI, sparing large health care expenditures. Although the urine culture is traditionally regarded as the gold standard of UTI, positive urine cultures may occur secondary to contamination or in cases of ABU, leading to a false diagnosis of UTI. In contrast we found pyuria to be a reliable marker to discriminate infection from colonization of the urinary tract. The sustained absence of an inflammatory response, on repeat UA within 24 h, constitutes strong evidence that infection is absent. Management of ABU is controversial; many experts recommend withholding antibiotics because eradication of low virulence organisms may be followed by colonization with more virulent species that cause pyelonephritis. Preliminary results of our ongoing treatment trial suggest that management of young febrile children with UTI as outpatients receiving oral cefixime is as efficacious as inpatient management with intravenous cefotaxime. Results of renal ultrasound and DMSA scan at the time of infection have not modified management in any patient. Accordingly selective rather than routine performance of ultrasound is recommended. A voiding cystourethrogram at 1 month and a DMSA scan 6 months later have been valuable in identifying patients with vesicoureteral reflux and renal scarring, respectively. Among patients initially identified as having acute pyelonephritis, the incidence of renal scarring at 6 months has been substantially more frequent (approximately 40%) than we had expected. However, the long term implications of small scars identified with renal scintigraphy remain to be determined.

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

BACKGROUND: To our knowledge, the risk of renal scarring in children with a urinary tract infection (UTI) has not been systematically studied. OBJECTIVE: To review the prevalence of acute and chronic renal imaging abnormalities in children after an initial UTI. METHODS: We searched Medline and Embase for English-, French-, and Spanish-language articles using the following terms: “Technetium 99mTc dimercaptosuccinic acid (DMSA),” “DMSA,” “dimercaptosuccinic,” “scintigra*,” “pyelonephritis,” and “urinary tract infection.” We included articles if they reported data on the prevalence of abnormalities on acute-phase (≤15 days) or follow-up (>5 months) DMSA renal scans in children aged 0 to 18 years after an initial UTI. Two evaluators independently reviewed data from each article. RESULTS: Of 1533 articles found by the search strategy, 325 full-text articles were reviewed; 33 studies met all inclusion criteria. Among children with an initial episode of UTI, 57% (95% confidence interval [CI]: 50–64) had changes consistent with acute pyelonephritis on the acute-phase DMSA renal scan and 15% (95% CI: 11–18) had evidence of renal scarring on the follow-up DMSA scan. Children with vesicoureteral reflux (VUR) were significantly more likely to develop pyelonephritis (relative risk [RR]: 1.5 [95% CI: 1.1–1.9]) and renal scarring (RR: 2.6 [95% CI: 1.7–3.9]) compared with children with no VUR. Children with VUR grades III or higher were more likely to develop scarring than children with lower grades of VUR (RR: 2.1 [95% CI: 1.4–3.2]). CONCLUSIONS: The pooled prevalence values provided from this study provide a basis for an evidence-based approach to the management of children with this frequently occurring condition.

IS URINE CULTURE NECESSARY TO RULE OUT URINARY TRACT INFECTION IN YOUNG FEBRILE CHILDREN

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.).

INTRA- AND INTEROBSERVER VARIABILITY IN INTERPRETATION OF DMSA SCANS USING A SET OF STANDARDIZED CRITERIA

Objectives. To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). Methods. In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age <24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. Results. Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 &mgr;g/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. Conclusions. On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children <24 months of age and those with infections caused by PRSP.

Acute Otitis Media in Children With Bronchiolitis

OBJECTIVE To determine whether the absence of pyuria on the enhanced urinalysis can be used to eliminate the diagnosis of urinary tract infection, avoiding the need for urine culture and sparing large health care expenditures. DESIGN Results of an enhanced urinalysis (hemocytometer counts and interpretation of Gram-stained smears) performed on uncentrifuged urine specimens obtained by catheter were correlated with urine cultures in young febrile children at the Childrens Hospital of Pittsburgh Emergency Department. In a group of 4253 children (95% febrile) less than 2 years of age, pyuria was defined as > or = 10 white blood cells/mm3, bacteriuria as any bacteria on any of 10 oil immersion fields in a Gram-stained smear and a positive culture as > or = 50,000 colony-forming units/ml. A subgroup of 153 children with their first diagnosed urinary tract infection were enrolled in a separate treatment trial, acute phase reactants (peripheral white blood cell count, erythrocyte sedimentation rate and C-reactive protein) were obtained and 99Tc-dimercaptosuccinic acid renal scans were performed. RESULTS The presence of either pyuria or bacteriuria and the presence of both pyuria and bacteriuria have the highest sensitivity (95%) and positive predictive value (85%), respectively, for identifying positive urine cultures. Because a white blood cell count in a hemocytometer is the technically simpler component of the enhanced urinalysis, we chose to analyze the false negative results and achievable cost savings of using pyuria alone as the sole criterion for omitting urine cultures. If in this study urine cultures had been performed only on specimens from children who had pyuria or were managed presumptively with antibiotics, cultures of 2600 (61%) specimens would have been avoided. Twenty-two of 212 patients with positive urine cultures would not have been identified initially. However, based on interpretation of acute phase reactants, initial 99Tc-dimercaptosuccinic acid scan results, response to management and incidence of renal scarring 6 months later, 14 of the 22 patients most likely had asymptomatic bacteriuria and fever from another cause. The remaining 8 patients probably had early urinary tract infection. CONCLUSIONS The analysis of urine samples obtained by catheter for the presence of significant pyuria (> or = 10 white blood cells/mm3) can be used to guide decisions regarding the need for urine culture in young febrile children.