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Ellen R Wald

Publications and source records attributed to Ellen R Wald.

At least 37 records · Page 2Linked to original sources

Reemergence of macrolide resistance in pharyngeal isolates of group a streptococci in southwestern Pennsylvania.

We previously reported on the emergence of macrolide-resistant pharyngeal isolates of group A streptococci (GAS) in our community. The purpose of the present study was to track longitudinal trends in macrolide resistance in these isolates in southwestern Pennsylvania. Testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered at the Children's Hospital of Pittsburgh and a local pediatric practice between September 2001 and May 2002. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion and PCR, respectively. Strain relatedness was determined by field inversion gel electrophoresis and emm gene sequence typing. A total of 708 isolates of GAS were recovered during the study period; 68 (9.6%) were macrolide resistant, while all isolates were sensitive to clindamycin. The monthly prevalence of macrolide resistance ranged from 0 to 41%. Only 21 of 573 (3.7%) strains recovered from September 2001 through March 2002 were macrolide resistant. A sudden increase in the rate of macrolide resistance (47 of 135 isolates [35%]) was seen in April and May 2002. Sixty-two isolates demonstrated the M phenotype (resistance to macrolide antibiotics), and six isolates demonstrated the MLS(B) phenotype (resistance to most macrolide, lincosamide, and streptogramin B antibiotics); these isolates were confirmed to be mef(A) and erm(A), respectively. Three unique mef(A) clones and four unique erm(A) clones were identified among the resistant isolates. The MIC at which 50% of isolates are inhibited (MIC(50)) for the mef(A) strains was 16 micro g/ml, while the MIC(50) for erm(A) strains was 8 micro g/ml. The finding of high levels of macrolide resistance among pharyngeal isolates of GAS for a second successive year in our community raises the concern that this problem may be more common in the United States than was previously appreciated. Longitudinal surveillance of isolates from multiple centers is needed to define the prevalence of antimicrobial agent-resistant GAS in the United States.

Anti-Bacterial Agents↗

Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine.

OBJECTIVE: To monitor clinical and microbiologic features including antimicrobial susceptibility and serogroup distribution of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of routine administration of the 7-valent pneumococcal conjugate vaccine (PCV7). DESIGN: A 9-year (January 1, 1994 through December 31, 2002) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at 8 children's hospitals in the United States with culture-proven invasive infections caused by S pneumoniae. RESULTS: When compared with the mean of the years 1994 to 2000, the annual number of invasive pneumococcal infections for children < or =24 months of age declined 58% in 2001 and 66% in 2002. If only the serogroups in the PCV7 are considered, the number of cases in children < or =24 months old declined 63% and 77% in 2001 and 2002, respectively. The greatest decrease was observed for serogroup-14 isolates. The number of isolates in nonvaccine serogroups increased 28% in 2001 and 66% in 2002 for children < or =24 months old. Nonvaccine serogroup-15 and -33 isolates had the greatest increase in number. The proportion of all isolates nonsusceptible to penicillin increased yearly from 1994 to 2000, reached a plateau in 2001 at 45%, and declined to 33% in 2002. Decrease in nonsusceptibility to penicillin occurred entirely in the isolates with penicillin minimum inhibitory concentration > or =2 microg/mL. Nonsusceptibility to penicillin increased slightly among nonvaccine-serotype isolates. Most infections after at least 2 doses of PCV7 were caused by nonvaccine-serotype isolates. CONCLUSIONS: Since the introduction of the PCV7, the number of invasive pneumococcal infections caused by vaccine-serogroup isolates among 8 US children's hospitals has decreased >75% among children < or =24 months old. In addition, penicillin resistance decreased in 2002 for the first time since our surveillance began in 1993-1994. However, we have noted that replacement may be developing with serogroups 15 and 33. Furthermore, penicillin resistance seems to be increasing among nonvaccine serogroups. Surveillance must be continued to detect the emergence of changes in the distribution of serotypes as well as antibiotic susceptibility.

Child↗

Group A streptococci among school-aged children: clinical characteristics and the carrier state.

OBJECTIVE: A 4-year longitudinal study of school-aged children was conducted to describe the clinical characteristics and epidemiologic features of infections with group A streptococci (GAS). METHODS: Between 1998 and 2002, surveillance throat cultures were performed twice per month (October to May) for a cohort of elementary school children in Pittsburgh, Pennsylvania. In addition, throat cultures were obtained during any respiratory illness. Erythromycin and clindamycin susceptibility testing was performed for all isolates. Molecular typing was performed with field-inversion gel electrophoresis. Representative isolates from each field-inversion gel electrophoresis group were emm typed. Strict definitions were used to characterize each GAS infection. Children were classified into 4 categories each year, ie, single episode, recurrent episodes, carriers of GAS, and no infections. RESULTS: A total of 48 to 100 children per year were studied for 4 years; 61 (49%) were male. The mean age was 9.6 years (range: 5-15 years). A total of 5658 throat cultures were performed; 878 (15.5%) were positive for GAS. Antimicrobial agents were used to treat 209 episodes of infection. Thirteen emm types were observed during the 4-year period. GAS were isolated most often from children who were carriers; isolates from single episodes were next most common. Children carried a single emm type for a mean of 10.8 weeks (range: 3-34 weeks). Carriers were likely to be classified again as carriers in subsequent years and frequently switched emm types. Sixty-two percent of the children had > or =1 year with no infections. CONCLUSIONS: GAS infections are common among school-aged children. The majority of positive throat cultures observed in this longitudinal study were obtained from children who were carriers of GAS. Carriers switched emm types but tended to become carriers repeatedly during the study. Practitioners should consider treating children known to be GAS carriers when they develop a new illness that is consistent with streptococcal pharyngitis, because they may acquire new emm types and be at risk for rheumatic heart disease.

Adolescent↗

Spectrum of clinical manifestations of West Nile virus infection in children.

Reports of clinical manifestations of West Nile virus (WNV) infections in children have been relatively rare. Four cases of WNV infection in children are described: the first report of prolonged encephalitis and fulminant hepatitis caused by WNV, and 3 other presentations of WNV, including the first report of ocular involvement in a child.

Adolescent↗

Listeriosis.

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Female↗

Epidemiology of acute otitis media caused by Streptococcus pneumoniae before and after licensure of the 7-valent pneumococcal protein conjugate vaccine.

We studied, by pulsed-field gel electrophoresis, multilocus sequence typing and penicillin-binding protein 2b amplicon-restriction profiles, pneumococcal isolates recovered from children with acute otitis media during 1 January-31 December 1999 and 2001. The proportion of nonvaccine serogroups increased from 14.8% (13/88) to 36.5% (23/63) from 1999 to 2001 (P<.01). Among children who received at least 2 doses of the pneumococcal 7-valent protein conjugate (PNC7) vaccine, 46.7% (7/15) of the isolates had nonvaccine serogroups, compared with 20.8% (26/125) of the isolates from children who did not receive the PNC7 vaccine (P=.05). Overall, the serogroups involved in capsular switching were 6-19-NT, 6-14-35, 15-19, and the 19-Spanish 23F clone. In 1999 and 2001, 30.8% (4/13) and 26.1% (6/23) of the nonvaccine serogroups were implicated in capsular switching, respectively. Continued surveillance will be of great importance as the distribution of the PNC7 vaccine increases.

Acute Disease↗

Otitis media.

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Acute Disease↗

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.

Antibiotic Prophylaxis↗

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.

Anti-Bacterial Agents↗

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.

Antiviral Agents↗

Macrolide resistance among middle ear isolates of Streptococcus pneumoniae observed at eight United States pediatric centers: prevalence of M and MLSB phenotypes.

BACKGROUND: Increasing macrolide resistance among middle ear isolates complicates treatment of otitis media in children. When macrolide resistance is mediated via an efflux pump (M phenotype), the MICs of erythromycin, clarithromycin and azithromycin are usually below 32 microg/ml, and the pneumococcus remains susceptible to clindamycin. The association of prior specific macrolide therapy with the isolation of a macrolide resistant strain has not been reported. OBJECTIVES: To determine the mechanism of macrolide resistance in Streptococcus pneumoniae recovered from the middle ears of children with otitis media and their association, if any, with ethnicity, age, serogroup/serotype and prior antibiotic therapy. METHODS: Middle ear isolates collected by members of the United States Pediatric Multicenter Pneumococcal Surveillance Group during a 6-year period from September 1994 through August 2000 were studied. Antibiotic susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Disc diffusion susceptibility to erythromycin and clindamycin was performed to categorize macrolide resistance mechanisms. The medical record was reviewed to determine demographics and history of previous antibiotic therapy. Isolates were serogrouped or serotyped by the capsular swelling method. RESULTS: Of the 1088 isolates available for testing, 51% were nonsusceptible to penicillin and 37% were nonsusceptible to erythromycin. Erythromycin resistance increased form 15% in 1994 through 1995 to 56% in 1999 through 2000. Seventy-five percent of macrolide-resistant strains were M phenotype. Macrolide resistance was less likely in isolates recovered from African-Americans and more likely in isolates obtained from children <3 years of age and from isolates obtained at time of tympanostomy tube placement. Neither erythromycin, nor clarithromycin nor azithromycin prescribed in the 30 days before infection was more likely than another to be associated with increased macrolide resistance. However, any macrolide alone or in combination with another antimicrobial taken before infection was associated with increased macrolide resistance among the S. pneumoniae organisms isolated from the middle ear. CONCLUSIONS: Macrolide resistance among middle ear isolates of S. pneumoniae increased during the 6-year study. The proportion of M phenotype remained constant at 75%, meaning that these isolates remain susceptible to clindamycin. Continued surveillance to document potential changes is essential.

Anti-Bacterial Agents↗

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.

Anti-Bacterial Agents↗