Judith M. Martin

Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America a

Abstract The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Prevalence of Streptococcal Pharyngitis and Streptococcal Carriage in Children: A Meta-analysis

OBJECTIVES: Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing of children who present with symptoms of pharyngitis. We conducted a meta-analysis to determine the (1) prevalence of streptococcal infection among children who presented with sore throat and (2) prevalence of streptococcal carriage among asymptomatic children. METHODS: We searched Medline for articles on pediatric streptococcal pharyngitis. We included articles in our review when they contained data on the prevalence of group A Streptococcus (GAS) from pharyngeal specimens in children who were younger than 18 years. Two evaluators independently reviewed, rated, and abstracted data from each article. Prevalence estimates were pooled in a meta-analysis and stratified according to age group. RESULTS: Of the 266 articles retrieved, 29 met all inclusion criteria. Among children of all ages who present with sore throat, the pooled prevalence of GAS was 37% (95% confidence interval [CI]: 32%–43%). Children who were younger than 5 years had a lower prevalence of GAS (24% [95% CI: 21%–26%]). The prevalence of GAS carriage among well children with no signs or symptoms of pharyngitis was 12% (95% CI: 9%–14%). CONCLUSIONS: Prevalence rates of GAS disease and carriage varied by age; children who were younger than 5 years had lower rates of throat cultures that were positive for GAS.

Executive Summary: Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America

The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

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 ≥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.

Structure and Distribution of an Unusual Chimeric Genetic Element Encoding Macrolide Resistance in Phylogenetically Diverse Clones of Group A Streptococcus

The resistance of group A Streptococcus (GAS) to macrolide antibiotics is now a worldwide problem. Preliminary sequencing of the genome of an erythromycin-resistant serotype M6 clone that was responsible for a pharyngitis outbreak in Pittsburgh, Pennsylvania, was conducted to determine the structure of the genetic element containing the mefA gene, which encodes a macrolide efflux protein. The mefA gene is associated with a 58.8-kb chimeric genetic element composed of a transposon inserted into a prophage. This element also encodes a putative extracellular protein with a cell-wall anchoring motif (LPKTG) located at the carboxyterminus. The mefA element was present in phylogenetically diverse GAS strains isolated throughout the United States. Culture supernatants, prepared after mitomycin C treatment, of a strain representing the outbreak clone contained mefA element DNA in a DNAse-resistant form. Together, these data provide new information about the molecular genetic basis of macrolide resistance and dissemination in GAS strains.

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

ABSTRACT 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 Childrens 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 MLSB 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 (MIC50) for the mef(A) strains was 16 μg/ml, while the MIC50 for erm(A) strains was 8 μg/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.

Food Insecurity: Could School Food Supplementation Help Break Cycles of Intergenerational Transmission of Social Inequalities?

OBJECTIVE: The aim of our study was to investigate the moderating effect of school food programs in schools in disadvantaged neighborhoods on the association between household food insecurity and scholastic difficulties among adolescents. METHODS: We analyzed data from the Social and Health Survey of Children and Adolescents in Quebec, Canada, which was conducted in 1999 and included 2346 adolescent students 13 and 16 years of age (and 1983 of their parents). Sample-weighted regression analyses were performed to determine the association between household food insecurity and school difficulties and to explore the moderating role of food supplementation programs with respect to this association. RESULTS: Household food insecurity, which was linked to the indicators of family socioeconomic status, was strongly associated with the indicators of scholastic difficulties. This association disappeared for adolescents who benefited from food supplementation programs in schools in disadvantaged neighborhoods. The risk of school activity limitation decreased from OR = 2.76 (95% confidence interval [CI]: 1.41–5.41) to OR = 1.57 (95% CI: 1.35–3.40), the risk of below-average grades in the language of instruction decreased from OR = 2.19 (95% CI: 1.28–3.74) to OR = 0.59 (95% CI: 0.21–1.63), the risk of repeating a year decreased from OR = 2.14 (95% CI: 1.35–3.40) to OR = 0.87 (95% CI: 0.42–1.81), and the risk of self-rated poor academic performance decreased from OR = 1.74 (95% CI: 1.08–2.81) to OR = 0.81(95% CI: 0.37–1.78). CONCLUSION: School food supplementation is a moderating factor in the association between household food insecurity and scholastic difficulties for adolescents.

Intrinsic Reduced Susceptibility of Serotype 6 Streptococcus pyogenes to Fluoroquinolone Antibiotics

BACKGROUND Fluoroquinolone resistance is common in Staphylococcus aureus, is increasing in Streptococcus pneumoniae, and is reported in Streptococcus pyogenes. METHODS We surveyed 384 clinical isolates of S. pyogenes, isolated during 2002-2003, for susceptibility to ciprofloxacin. We performed nucleotide sequencing of the parC and gyrA genes and determined the M/emm type for selected isolates. Additionally, we analyzed M/emm type 6 S. pyogenes isolated during 1918-2003 from diverse locations. RESULTS Of the survey isolates, 10.9% had reduced zones of inhibition to ciprofloxacin in the disk-diffusion test and had elevated minimum inhibitory concentrations to other fluoroquinolones, compared with those of fully susceptible isolates. Of the resistant isolates, 90.5% were M/emm type 6, and all sequenced M/emm type 6 isolates contained a serine-to-alanine substitution at position 79 in parC. Strikingly, the same findings were also present in macrolide-resistant isolates from a recent outbreak of S. pyogenes infection in Pittsburgh and in the Lancefield reference strain of M type 6, which was isolated in 1918, decades before the development of fluoroquinolone antibiotics. CONCLUSION M/emm type 6 S. pyogenes has intrinsic reduced susceptibility to fluoroquinolones, as a result of a polymorphism in parC. This finding was also demonstrated in erythromycin-resistant M/emm type 6 S. pyogenes, which raises concern for the emergence of multidrug-resistant S. pyogenes.

Treatment of shigellosis with cefixime: two days vs. five days.

Background. Although the recommended standard course of therapy for shigellosis is 5 days of oral ampicillin or trimethoprim‐sulfamethoxazole therapy, successful outcome has been reported in adults treated with abbreviated courses of antibiotics. The purpose of this study was to compare short course (2‐day) vs. 5‐day therapy with cefixime for treatment of diarrheal disease caused by Shigella sonnei in children. Methods. This was a prospective, randomized, double blind, placebo‐controlled study. Patients were eligible if they were at least 6 months of age and presented to the Childrens Hospital of Pittsburgh during an outbreak of diarrhea caused by S. sonnei, with (1) a history of fever and diarrhea (at least three loose or watery stools per day), (2) bloody diarrhea or (3) diarrhea and known exposure to an individual with documented shigellosis. Patients were randomized to receive either 2 days of cefixime (8 mg/kg/day) given once daily followed by 3 days of placebo or 5 days of cefixime. Telephone follow‐up was performed on Days 3, 7 and 14 after enrollment. Follow‐up stool cultures were obtained on Day 7 to assess bacteriologic cure. There were standardized definitions for cure, improvement, failure and relapse. Results. Forty‐seven patients were enrolled. Eleven were eliminated from analysis because their stool cultures were not positive for S. sonnei. There were 36 evaluable patients, 21 in the 2‐day group and 15 in the 5‐day group. Patients ranged in age from 6 months to 17 years. Forty‐four percent of the subjects were male. Symptoms were improved or had resolved by Day 3 of therapy in all patients. There were 8 patients who experienced a clinical relapse: 5 of 21 (24%) patients in the 2‐day treatment group and 3 of 15 (20%) in the 5‐day group. There were 13 patients who experienced a bacteriologic failure (defined as the occurrence of a positive culture at the Day 7 follow‐up visit), 11 of 20 (55%) in the 2‐day group and 2 of 14 (14%) in the 5‐day group (P < 0.02). Conclusion. Two‐ and 5‐day treatment courses with cefixime for treatment of diarrheal disease caused by S. sonnei result in similar rates of clinical cure and clinical relapses; however, there was a higher rate of bacteriologic failure with shorter course therapy.

Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children

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 .).