Biomedical subjects
Ellen R Wald
Publications and source records attributed to Ellen R Wald.
Imaging studies after a first febrile urinary tract infection in young children.
BACKGROUND: Guidelines from the American Academy of Pediatrics recommend obtaining a voiding cystourethrogram and a renal ultrasonogram for young children after a first urinary tract infection; renal scanning with technetium-99m-labeled dimercaptosuccinic acid has also been endorsed by other authorities. We investigated whether imaging studies altered management or improved outcomes in young children with a first febrile urinary tract infection. METHODS: In a prospective trial involving 309 children (1 to 24 months old), an ultrasonogram and an initial renal scan were obtained within 72 hours after diagnosis, contrast voiding cystourethrography was performed one month later, and renal scanning was repeated six months later. RESULTS: The ultrasonographic results were normal in 88 percent of the children (272 of 309); the identified abnormalities did not modify management. Acute pyelonephritis was diagnosed in 61 percent of the children (190 of 309). Thirty-nine percent of the children who underwent cystourethrography (117 of 302) had vesicoureteral reflux; 96 percent of these children (112 of 117) had grade I, II, or III vesicoureteral reflux. Repeated scans were obtained for 89 percent of the children (275 of 309); renal scarring was noted in 9.5 percent of these children (26 of 275). CONCLUSIONS: An ultrasonogram performed at the time of acute illness is of limited value. A voiding cystourethrogram for the identification of reflux is useful only if antimicrobial prophylaxis is effective in reducing reinfections and renal scarring. Renal scans obtained at presentation identify children with acute pyelonephritis, and scans obtained six months later identify those with renal scarring. The routine performance of urinalysis, urine culture, or both during subsequent febrile illnesses in all children with a previous febrile urinary tract infection will probably obviate the need to obtain either early or late scans.
Management of nontuberculous mycobacterial cervical lymphadenitis.
OBJECTIVE: To review the treatment and outcome of patients with nontuberculous mycobacterial (NTM) cervical lymphadenitis. DESIGN: Retrospective chart review. SETTING: Tertiary care children's hospital. PATIENTS: Thirty consecutive immunocompetent patients (median age, 32 months; age range, 11-147 months) diagnosed as having NTM cervical lymphadenitis over a 77-month period. INTERVENTIONS: Primary therapy for 34 foci of NTM cervical lymphadenitis in 30 children consisted of excisional biopsy (n = 8), incision and drainage procedures (n = 14), fine-needle aspiration biopsy (n = 7), observation only (n = 4), and antimycobacterial chemotherapy only (n = 1). MAIN OUTCOME MEASURES: (1) Time to cure, (2) recurrent adenitis, and (3) complications associated with therapy were determined for each therapeutic option. The average duration of follow-up was 32 months (range, 6-78 months). RESULTS: Nearly all patients (97%) were cured of their disease regardless of which therapeutic option was used. Excisional biopsy, while associated with transient marginal mandibular nerve injury in 1 patient, typically resulted in the most rapid resolution of disease. Observation alone did result in eventual cure, although the disease course was protracted. Simple incision and drainage without curettage was associated with prolonged postoperative wound discharge and hypertrophic scarring. CONCLUSIONS: A variety of therapeutic options were used in children with NTM cervical lymphadenitis. Resolution of infection was an eventual outcome regardless of treatment option, although duration of disease, potential for facial nerve injury, and incidence of hypertrophic scarring varied among the different treatments. An individualized management approach is recommended, with excisional biopsy as the preferred option when feasible.
Acute otitis media: more trouble with the evidence.
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Treatment of children with congenital cytomegalovirus infection with ganciclovir.
BACKGROUND: Congenital cytomegalovirus (CMV) infection affects approximately 1% of live births in the US. Ten percent of these infants have symptoms at birth and another 10 to 15% acquire hearing loss or developmental problems. Congenital CMV is the most common cause of nonhereditary sensorineural hearing loss in children, and progressive hearing loss is common. To arrest the natural progression of congenital CMV, children referred to our center were treated with a prolonged course of ganciclovir. METHODS: Medical records of children with congenital CMV who were treated with ganciclovir were reviewed to tabulate their presenting symptoms, duration of treatment, audiologic and developmental assessments and complications. RESULTS: We treated nine children with symptomatic CMV with iv ganciclovir at a median age of 10 days (range, 3 days to 11 months). Findings at diagnosis included microcephaly (five of nine); petechiae (five of nine); thrombocytopenia (seven of nine); and intracranial calcifications (six of eight). Hearing loss was noted before therapy in five of nine. The median duration of iv and subsequent oral ganciclovir was 1 year and 0.83 year, respectively. Median follow-up was 2 years (range, 1 to 7 years). No child had progression of hearing loss; improvement occurred in two. Seven children had at least one complication of ganciclovir therapy: central venous catheter/site infection (six); catheter malfunction (three); and neutropenia (one). CONCLUSION: Of nine children none treated with ganciclovir for congenital CMV had detectable progressive hearing loss. Complications associated with iv therapy occurred frequently. Currently available oral analogues of ganciclovir may facilitate earlier and more prolonged therapy for children with symptomatic congenital CMV and should be subjected to randomized controlled trials.
In vitro activities of cethromycin (ABT-773), a new ketolide, against Streptococcus pneumoniae strains that are not susceptible to penicillin or macrolides.
Pneumococcal resistance to antimicrobials presents problems to physicians for empirical treatment of acute otitis media (AOM). Three hundred thirty-three isolates of Streptococcus pneumoniae selected for nonsusceptibility to penicillin (MIC >0.1 microg/ml) from the middle ear (n = 325) or mastoid (n = 8) of children seen between 1994 and 2000 at four children's hospitals in the United States were tested by broth microdilution for susceptibility to nine antibiotics. Using NCCLS 2002 breakpoints, resistance to the following drugs was as indicated: amoxicillin, 1%; azithromycin, 71%; cefprozil, 71%; ceftriaxone, 2%; cefdinir, 98%; erythromycin, 70%; levofloxacin, 0%; and trimethoprim-sulfamethoxazole, 93%. Of the penicillin- and erythromycin-nonsusceptible isolates, 97% were inhibited by cethromycin (ABT-773) and 83% were inhibited by telithromycin at a concentration of <or=0.125 microg/ml. Macrolide resistance among penicillin-nonsusceptible pneumococci increased from 44 to 80% in the 6 years of the study from which the isolates were selected; however, the proportion of isolates with M or MLS(B) phenotypes remained constant over the time period (53 and 18%, respectively). Prior treatment with a macrolide or clindamycin alone or in combination with a beta-lactam resulted in 94 or 85% of isolates causing infections being macrolide and or clindamycin resistant. No prior individual macrolide (azithromycin, erythromycin, or clarithromycin) resulted in more macrolide resistance or in a more prevalent resistance phenotype. The ketolides appear to be active antimicrobials against penicillin- and macrolide-resistant pneumococci.
Incidence of invasive pneumococcal disease in children 3 to 36 months of age at a tertiary care pediatric center 2 years after licensure of the pneumococcal conjugate vaccine.
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Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh.
BACKGROUND: Resistance to erythromycin has been very uncommon among group A streptococci in the United States. METHODS: As part of a longitudinal study, we obtained surveillance throat cultures twice monthly and with each new respiratory tract illness from children in kindergarten through grade 8 at one school in Pittsburgh. Screening for resistance to erythromycin and clindamycin was initially accomplished with use of the Kirby-Bauer disk-diffusion test. The minimal inhibitory concentration of resistant isolates was determined by the E test. A double disk-diffusion test was used to characterize the resistance phenotype, and the polymerase-chain-reaction assay was used to identify the resistance gene. The molecular relatedness of strains was determined by field-inversion gel electrophoresis. RESULTS: A total of 1794 throat cultures were obtained from 100 children between October 2000 and May 2001, of which 318 cultures (18 percent) from 60 of the children were positive for group A streptococci. Forty-eight percent of these isolates (153 of 318) were resistant to erythromycin. None were resistant to clindamycin. Results of the double disk-diffusion test indicated the presence of the M phenotype of erythromycin resistance. Molecular typing indicated that the outbreak was due to a single strain of group A streptococci. Of 100 randomly selected isolates of group A streptococci obtained from the community between April and June 2001, 38 were resistant to erythromycin. CONCLUSIONS: In January 2001, during a longitudinal study of schoolchildren, we detected the emergence of erythromycin resistance in pharyngeal isolates of group A streptococci. This clonal outbreak also affected the wider community.
Antibiotic prescribing by primary care physicians for children with upper respiratory tract infections.
OBJECTIVES: To determine if the rate of appropriate antibiotic use in the treatment of children with bronchitis, viral upper respiratory tract infections, sinusitis, otitis media, and pharyngitis has changed in recent years and to identify factors that are associated with the use of inappropriate antibiotic therapy. DESIGN: The National Ambulatory Medical Care Survey was used to examine the antimicrobial prescribing habits of physicians who provide primary care for children. Data were analyzed from 1995-1998. SETTING: Office-based physician practices. PARTICIPANTS: Pediatricians, family physicians, and generalists completing survey forms for patients younger than 18 years. MAIN OUTCOME MEASURE: The appropriate use of antibiotics for upper respiratory tract infections. RESULTS: Multivariate analyses were used to examine factors associated with the use of inappropriate antibiotics to treat either upper respiratory tract infections or bronchitis. Patients seen in 1998 and diagnosed as having upper respiratory tract infections were 0.69 (95% confidence interval, 0.59-0.81) times less likely to be treated with antibiotics compared with patients seen in 1995. Multivariate analyses were also used to assess factors associated with the use of antibiotics with a suboptimal therapeutic profile for the treatment of either sinusitis or otitis media. Children diagnosed as having either sinusitis or otitis media were 0.3 (95% confidence interval [CI], 0.16-0.48) times less likely to receive antibiotics with a suboptimal therapeutic effect in 1998 compared with 1995. CONCLUSIONS: Physicians are slowly improving their antibiotic prescribing patterns but the use of inappropriate antibiotics is still common. Almost half of patients with upper respiratory tract infections receive antibiotics.
Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin.
BACKGROUND: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci. PURPOSE AND DESIGN: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy. RESULTS: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents. No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79% vs. 81%); deaths (2% vs. 3%); seizures after enrollment (22% vs. 21%); and severe sequelae (14% vs. 14%). Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen. None of the evaluable patients experienced significant abnormalities of liver function during treatment. One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge. The episode resolved with liver function tests returning to normal within 2 months. CONCLUSIONS: We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis. These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections.
Invasive pneumococcal infections in children with asplenia.
BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. OBJECTIVE: To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. METHODS: Children with S. pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2,581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.
Ecthyma gangrenosum: considerations in a previously healthy child.
Ecthymagangrenosum is a skin lesion that is most commonly caused by. Although ecthyma gangrenosum usually develops in patients with underlying immunodeficiencies or chronic diseases, there have been reports of its appearance in previously healthy children. A review of such patients in the English literature showed that most of them had either previously undetected immunodeficiencies or transient risk factors that predisposed them to the development of ecthyma gangrenosum. We report a patient without apparent antecedent predisposing risk factors for ecthyma gangrenosum who developed chronic neutropenia 1 week after presentation. It is important for the primary care provider to recognize ecthyma gangrenosum, treat it with appropriate antimicrobial agents and investigate the patient for occult immunodeficiencies.
Route of antibiotic administration for conjunctivitis.
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The sinusitis debate.
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Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae.
OBJECTIVE: The frequency of children who are hospitalized with pneumococcal pneumonia complicated by necrosis, empyema/complicated parapneumonic effusion, and lung abscess seems to be increasing. The factors that contribute to this increase are unclear; therefore, the objective of this study was to describe and compare the relative frequency, clinical characteristics, and outcome of hospitalized children with complicated pneumonia with those of children with uncomplicated pneumonia caused by Streptococcus pneumoniae in the era of antibiotic resistance. METHODS: A multicenter, retrospective study of 8 children's hospitals in the United States was undertaken. A total of 368 children who were hospitalized with pneumococcal pneumonia identified from patients enrolled in the US Pediatric Multicenter Pneumococcal Surveillance Study over the period from September 1, 1993, to January 31, 2000 were studied. Demographic and clinical variables, antibiotic susceptibility, pneumococcal serotypes, antimicrobial therapy, and clinical outcome in hospitalized children with complicated versus uncomplicated pneumococcal pneumonia were measured. RESULTS: A total of 368 patients with pneumococcal pneumonia were identified. Of the 368 isolates, 47 (12.8%) were intermediate and 37 (10.1%) were resistant to penicillin; 18 (5%) were intermediate to ceftriaxone, and 9 (2.5%) were resistant to ceftriaxone. A total of 133 patients met the criteria for complicated pneumonia and had a chest tube placed; 56 of these patients subsequently underwent decortication. The proportion of hospitalized patients with complicated pneumococcal pneumonia increased progressively over the study period from 22.6% in 1994 to 53% in 1999. Patients with complicated disease were older (median age: 45 vs 27 months) and significantly more likely to be of white race and have chest pain on presentation compared with patients with uncomplicated disease. Patients who had complicated disease and underwent decortication were more likely to have pleural fluid lactate dehydrogenase levels of >7500 IU/L compared with those patients who had chest tube placement alone. Fifty-three percent of children who were > or =61 months of age and were hospitalized had complicated pneumonia. This group of children accounted overall for 42% of the patients with complicated pneumonia, 48.2% of the patients who subsequently underwent decortication, and 44% of the patients who had received a course of antibiotics before diagnosis. Pneumococcal serotypes 1, 6, 14, and 19 were the most prevalent serotypes causing disease, with serotype 1 causing 24.4% of the complicated cases versus 3.6% of the uncomplicated cases. Ninety-eight percent of the patients in both groups recovered from their pneumonia. Antibiotic resistance was not found to be more prevalent in those patients with complicated disease. CONCLUSIONS: The relative frequency of complicated disease in hospitalized children with pneumococcal pneumonia is increasing. Patients with complicated pneumococcal disease were older and significantly more likely to be of white race compared with those patients with uncomplicated disease. Pneumococcal serotype 1 caused significantly more disease in patients with complicated versus uncomplicated pneumonia. Patients with complicated disease were not more likely to be infected with an antibiotic-resistant isolate.