Treatment of acute otitis media in children under 2 years of age.

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.).

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.

Emergence of Streptococcus pneumoniae serogroups 15 and 35 in nasopharyngeal cultures from young children with acute otitis media.

BACKGROUND: Surveillance of children with acute otitis media (AOM) for nasopharyngeal colonization with Streptococcus pneumoniae before, during and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) indicated the near-complete elimination of PCV7 strains and the emergence of pneumococcal serotype 19A. METHODS: To determine effects of the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal nasopharyngeal colonization, we obtained nasopharyngeal cultures from 228 children 6 through 23 of age months presenting with a new episode of AOM during 2012 and 2013 and enrolled in an ongoing clinical trial of antimicrobial efficacy. All children had received at least 2 doses of PCV13. The S. pneumoniae isolates were subjected to serotyping and testing for antimicrobial susceptibility. We compared the findings with results obtained in 3 earlier studies. RESULTS: We found nasopharyngeal colonization with S. pneumoniae in 113 (50%) of the children with AOM. PCV7 and PCV13 serotypes accounted for 2% and 12%, respectively, of the pneumococcal isolates. Of the 14 PCV13 isolates, 8 were serotype 19A. Nonvaccine serotypes accounted for 69% of the isolates. Most frequently occurring were subtypes of serotype 15 (23%) and serotype 35B (9%). Overall, 33% of the isolates were penicillin nonsusceptible, a proportion not significantly different from proportions found in our 3 earlier studies (26%, 36% and 37%, respectively). Serotypes 15 and 35B accounted for 51% of penicillin-nonsusceptible isolates. CONCLUSIONS: Expansion of contents of pneumococcal vaccine administered to children is followed by not-fully-predictable changes in nasopharyngeal pneumococcal colonization. Continued surveillance is required to help inform future vaccine development.

Are nasopharyngeal cultures useful in diagnosis of acute bacterial sinusitis in children?

The diagnosis of acute bacterial sinusitis can be challenging because symptoms of acute sinusitis and an upper respiratory tract infection (URI) overlap. A rapid test, if accurate in differentiating sinusitis from URI, could be helpful in the diagnostic process. We examined the utility of nasopharyngeal cultures in identifying the subgroup of children with a clinical diagnosis of acute sinusitis who are least likely to benefit from antimicrobial therapy (those with completely normal sinus radiographs). Nasopharyngeal swabs were collected from 204 children meeting a priori clinical criteria for acute sinusitis. All children had sinus X-rays at the time of diagnosis. To determine if negative nasopharyngeal culture results could reliably identify the subgroup of children with normal radiographs, we calculated negative predictive values and negative likelihood ratios. Absence of pathogens in the nasopharynx was not helpful in identifying this low-risk subgroup.

Pneumococcal resistance and serotype 19A in Pittsburgh-area children with acute otitis media before and after introduction of 7-valent pneumococcal polysaccharide vaccine.

METHODS: Before and after introduction of pneumococcal conjugate vaccine (PCV7), the authors obtained nasopharyngeal (NP) specimens from 3 groups of children aged 6 to 23 months with acute otitis media (AOM): group 1 (pre-PCV7), group 2 (early post-PCV7), and group 3 (late post-PCV7). RESULTS: Of the Streptococcus pneumoniae isolates, the proportion that were vaccine serotypes (VTs) declined progressively (60.4% vs 48.6% vs 5.2% in groups 1, 2, and 3, respectively; P < .001). Concurrently, increases occurred in the proportion of penicillin-nonsusceptible isolates (minimum inhibitory concentration >0.1 µg/mL; 26.7% vs 37.8% vs. 38.5%; P = .12); the proportion of isolates that were serotype 19A (4.0% vs 0% vs 25.9%; P < .001); and the proportion of 19A isolates that were penicillin-nonsusceptible (0% in group 1, 68.6% in group 3; P = .004). CONCLUSION: Shifts in pneumococcal serotype distribution and increases in penicillin nonsusceptibility among pneumococcal isolates from children with AOM underscore the need for continuing bacteriological surveillance for future vaccine development.

Continued high caseload of rheumatic fever in western Pennsylvania: Possible rheumatogenic emm types of streptococcus pyogenes.

OBJECTIVE: To evaluate the occurrence of cases of acute rheumatic fever (ARF) in western Pennsylvania although there has been a marked reduction of cases of ARF in the United States overall. STUDY DESIGN: From 1994 to 2003, the cases of ARF evaluated at Children's Hospital of Pittsburgh were reviewed. In addition, throat cultures were performed on a subset of these children and their family members beginning in 1995. Molecular typing was performed on isolates of the group A streptococcus (GAS) recovered, using field inversion gel electrophoresis (FIGE) and emm typing. RESULTS: There were 121 new cases of ARF from 1994 to 2003. Of these, 57% were male. The median age was 10 years. The majority of children (57%) had carditis with or without another manifestation of ARF. The results of throat cultures were available for 231 persons; 36% (30/84) of the children with ARF and 14% (20/147) of family members were positive for GAS. Eight emm types were observed (emm 1, 2, 6, 12, 18, 28, 75, and 89). Data suggest that emm type 12 may be a rheumatogenic strain. CONCLUSION: ARF remains a problem in western Pennsylvania. Identification of emm types associated with cases should enlighten vaccine development.

Streptococcus pyogenes isolates with high-level macrolide resistance and reduced susceptibility to telithromycin associated with 23S rRNA mutations.

Seven high-level macrolide-resistant Streptococcus pyogenes isolates had reduced activity to telithromycin but were negative for methylation and efflux genes. All were of the constitutive phenotype, were clonally related (emm type 12 and MLST type 36), and had identical dual mutations (A2058G and U2166C) in domain V of 23S rRNA.

Multicentre surveillance of the prevalence and molecular epidemiology of macrolide resistance among pharyngeal isolates of group A streptococci in the USA.

OBJECTIVES: Rates of macrolide resistance in group A streptococci (GAS) were reported to be low in the US in the 1990s. However, we documented an unexpectedly high rate of macrolide resistance among GAS in Pittsburgh, PA, in 2001 and 2002. In an effort to define the current prevalence of macrolide-resistant GAS in the US, a multicentre surveillance project was initiated. METHODS: Between October 2002 and May 2003, 50 pharyngeal GAS isolates per month were requested from each of the nine participating sites representing a wide geographical distribution. Standard susceptibility testing was performed and the macrolide resistance phenotype was assessed using double-disc diffusion testing. Monthly and annual rates of macrolide resistance were calculated for each site. An adjusted overall rate of macrolide resistance was determined to account for differences in the numbers of GAS isolates sent from each centre. RESULTS: Overall, 171 of the 2797 collected isolates of GAS (6.1%) were resistant to erythromycin. The adjusted overall resistance rate was 5.2%. Rates of macrolide resistance varied by site (range 3.0-8.7%) and also by month (<2% to >10%). The M phenotype of macrolide resistance accounted for >60% of all macrolide-resistant isolates recovered in this study. CONCLUSIONS: These data suggest an increasing prevalence and broad geographical distribution of macrolide-resistant GAS in the US, indicating the need for ongoing local and national longitudinal surveillance to define the extent of this problem.

In vitro activity of telithromycin against macrolide-susceptible and macrolide-resistant pharyngeal isolates of group A streptococci in the United States.

In vitro susceptibility testing of 2,797 group A streptococcus (GAS) isolates demonstrated that telithromycin was fully active against all macrolide-susceptible strains and among 80 of 115 macrolide-resistant GAS expressing the M phenotype. Telithromycin resistance was identified in 2 of 45 strains expressing the inducible macrolide-lincosamide-streptogramin B phenotype and four of nine isolates expressing the constitutive macrolide-lincosamide-streptogramin B resistance phenotype.

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.

Classification of M nontypeable group A streptococcus with the use of field inversion gel electrophoresis.

Group A streptococcus (GAS) are traditionally classified based on M and T protein antigens. However, many strains do not react with available M antisera and are classified as M nontypeable (M NT). M and T typing, field inversion gel electrophoresis (FIGE), and 5' emm gene sequencing were performed on 24 M NT GAS isolates. FIGE patterns of the M NT isolates were compared by visual inspection and by computer analysis with the patterns of 139 isolates representing 72 M-types of GAS. Seven different FIGE patterns (I-VII) were seen among the M NT isolates. FIGE patterns I and III were identical or closely related to patterns seen with M12 and M22 isolates. The computer analysis determined the following relationships: pattern IV to M5, pattern VI to M61, and pattern VII to M59. Thus, the emm gene sequence correlated with the computer analysis of the FIGE pattern for each isolate. FIGE can be useful to help distinguish clinical isolates of GAS in an epidemiological study.

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.