Searching for the Holy Grail of acute otitis media.
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Biomarkers↗
Biomedical subjects
S L Block
Publications and source records attributed to S L Block.
Restricted use of antibiotic prophylaxis for recurrent acute otitis media in the era of penicillin non-susceptible Streptococcus pneumoniae.
OBJECTIVE/INTERVENTION: To compare the annual rates of acute otitis media (AOM) episodes, antibiotic days, and ventilating tube insertion during the first 3 years of life before and after a practice change to restrict use of antibiotic chemoprophylaxis for recurrent AOM. METHODS SETTING: The sole pediatric private practice in a rural Kentucky community. PATIENTS: Population-based sample of all children born consecutively in two different 13 month intervals. Cohort 1 (n=251) was born before and Cohort 2 (n=274) was born after restricted use of chemoprophylaxis and documented emergence of widespread penicillin non-susceptible Streptococcus pneumoniae (PNSP). DESIGN: Retrospective case cohort comparison. MAIN OUTCOME MEASURES: Suppurative AOM diagnosed by validated experienced otoscopists using stringent tympanic membrane criteria. RESULTS: Children were mostly white with the majority (50-65%) enrolled in daycare during each year. The first episode of AOM was experienced by 6 and 12 months of age in 64 and 86%, respectively. Rates of children with recurrent AOM in Cohorts 1 and 2 were 28 and 31% in Year 1, 17 and 23% in Year 2, and 7 and 10% in Year 3, respectively. Rates of new onset AOM and persistent AOM episodes were similar between cohorts in the first 2 years. Number of days of antibiotic prophylaxis were reduced from 11.2 to 3.4 days in Year 1, from 11.9 to 2.6 days in Year 2, and from 6.9 to 0.7 days in Year 3, respectively (P<0.0001 for each year). Total antibiotic days for Years 1, 2 and 3 were reduced commensurately with prophylactic days from 61.7 to 55.5 days (nonsignificant), from 56.3 to 45.8 days (P=0.047), and from 38.7 to 25.7 days (P<0.0001), respectively. For each year a non-significant trend for increased ventilating tube placement from Cohort 1 to Cohort 2, respectively, was observed, 2 versus 2.2%, 4 versus 5.8%, and 0.8 versus 2.6%. Daycare attendance and white race were consistently significant risk factors for AOM and recurrent AOM. CONCLUSIONS: In the era of PNSP, restricted use of antibiotic chemoprophylaxis for recurrent AOM was not associated with significantly increased rates of new onset AOM episodes or tube placement in the first 24 months of life. Total antibiotic days were also significantly reduced in Cohort 2 during Years 2 and 3.
Acute Disease↗
Microbiology of acute otitis media recently treated with aminopenicillins.
INTRODUCTION: Sparse recent data are available in the United States regarding the pathogens of acute otitis media (AOM) most likely to be recovered from children recently treated with the two most frequently prescribed antibiotics, amoxicillin or amoxicillin/clavulanate (AMC). METHODS: Of the 704 rural Kentucky children with culture-positive AOM who underwent a single tympanocentesis or culture of otorrhea between 1992 and 1998, 96 pathogens were recovered from 90 children during therapy or within 7 days posttherapy with an aminopenicillin. Identification and susceptibility testing of AOM pathogens were performed by routine National Committee for Clinical Laboratory Standards methods. RESULTS: Pathogens recovered from children with AOM recently treated (0 to 7 days) with amoxicillin (n = 38) and AMC (n = 58), respectively, were as follows: Haemophilus influenzae (beta-lactamase-negative), 16 and 29%; H. influenzae (beta-lactamase-positive), 11 and 22%; penicillin-susceptible Streptococcus pneumoniae, 26 and 12%; intermediately penicillin-nonsusceptible S. pneumoniae (PNSP), 20 and 10%; resistant PNSP 13 and 17%; Moraxella catarrhalis (beta-lactamase-positive), 13 and 7%; and Streptococcus pyogenes, 3 and 2%. H. influenzae was also isolated from 8 (75%) of 12 children treated with high dose AMC ( approximately 80 mg/kg/day amoxicillin component). Significantly fewer children recently treated with amoxicillin were otitis-prone than those given AMC (24% vs. 74%, P < 0.0001). CONCLUSIONS: The predominant pathogen recovered from children with AOM recently treated with amoxicillin was S. pneumoniae (59%) rather than beta-lactamase-producing organisms (24%). H. influenzae was the predominant (51%) pathogen, rather than PNSP (27%), recovered from children recently treated with AMC.
Acute Disease↗
Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.
OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.
Administration, Intranasal↗
Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.
The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.
Administration, Intranasal↗
Five-day cefdinir course vs. ten-day cefprozil course for treatment of acute otitis media.
OBJECTIVE: To compare the clinical efficacy of a 5-day cefdinir course with a 10-day cefprozil course in the treatment of pediatric acute otitis media (AOM). DESIGN: Comparative, investigator-blinded multicenter trial. SETTING: Primary care, ambulatory. PATIENTS: Children ages 6 months through 12 years with clinical symptoms and tympanic membrane signs of AOM, plus tympanometric-confirmed middle ear effusion in at least 1 ear. Of the 435 patients enrolled in the study, 373 were evaluable. INTERVENTION: Patients received cefdinir 14 mg/ kg/day divided twice a day for 5 days or cefprozil 30 mg/kg/day divided twice a day for 10 days. MAIN OUTCOME MEASURES: Clinical resolution of tympanic membrane signs and symptoms of AOM determined at end of therapy on Study Days 9 to 11. RESULTS: The clinical cure rate at end of therapy was 80% (152 of 190) for cefdinir-treated patients and 82.5% (151 of 183) for cefprozil-treated patients (95% confidence interval, 10.43% to 5.4%). Diarrhea and overall adverse reactions, respectively, occurred in 7.8 and 13% of cefdinir-treated patients and in 4.2 and 12% of cefprozil-treated patients. CONCLUSIONS: A short course 5-day regimen of cefdinir was as clinically effective and well-tolerated as a 10-day regimen of cefprozil in the treatment of nonrefractory AOM.
Acute Disease↗
Five-day twice daily cefdinir therapy for acute otitis media: microbiologic and clinical efficacy.
OBJECTIVE: To examine the microbiologic and clinical efficacy of a 5-day course of cefdinir in the treatment of tympanocentesis-documented acute otitis media (AOM). DESIGN: Open label noncomparative trial. SETTING: Primary care, ambulatory. PATIENTS: Children ages 6 months through 12 years with signs of AOM and middle ear effusion confirmed by tympanometry in at least one ear. INTERVENTION: Patients underwent tympanocentesis at baseline and received cefdinir 7 mg/kg twice a day for 5 days. MAIN OUTCOME MEASURES: Presumptive eradication of middle ear pathogens determined by clinical cure of signs and symptoms of AOM at end of therapy (Study Days 7 to 9) and Visit 3 (Study Days 16 to 21). RESULTS: A total of 125 of 177 enrolled children had 134 pathogens isolated by tympanocentesis: Streptococcus pneumoniae, 69 (51.5%); Haemophilus influenzae 44 (32.8%; beta-lactamase-positive in 18 of 44 strains); beta-lactamase-positive Moraxella catarrhalis, 15 (11.2%); and Streptococcus pyogenes, 6 (4.5%). The clinical cure rates by patient in the microbiologically and overall clinically evaluable groups, respectively, were 73% (84 of 115) and 77.4% (130 of 168) at the end of therapy visit and 57.4% (66 of 115) and 61.9% (104 of 168) at Visit 3. Presumptive eradication rates at end of therapy were 8 of 11 (72.7%) and 4 of 8 (50%) for patients with penicillin-intermediate and -resistant S. pneumoniae isolates, respectively. Adverse reactions occurred in 16% of patients, with diarrhea (11%) occurring most frequently. CONCLUSIONS: A 5-day regimen of cefdinir was effective in the eradication of the common causative pathogens of nonrefractory AOM, including intermediate penicillin-resistant S. pneumoniae and beta-lactamase-producing organisms. Cefdinir should be considered a suitable second line antibiotic for AOM.
Acoustic Impedance Tests↗
Comparative safety and efficacy of cefdinir vs amoxicillin/clavulanate for treatment of suppurative acute otitis media in children.
OBJECTIVE: Two dosage regimens of cefdinir were compared with amoxicillin/clavulanate for the treatment of suppurative acute otitis media (AOM) in children. METHODS: This was an investigator-blinded, randomized, comparative, multicenter trial, in which tympanocentesis was performed in 384 patients, ages 6 months to 12 years, who had nonrefractory AOM. Patients were randomized to receive one of three 10-day treatment regimens: cefdinir 14 mg/kg daily (QD; n = 128); cefdinir 7 mg/kg twice a day (BID; n = 128); or amoxicillin/clavulanate 40/10 mg/kg/day divided for use three times a day (TID; n = 128). RESULTS: Of the 384 enrolled patients 303 were evaluable for clinical efficacy. Clinical success rates were statistically equivalent for the 3 treatment groups at the end of therapy: 85 of 102 (83.3%) for cefdinir QD; 81 of 101 (80.2%) for cefdinir BID; 86 of 100 (86%) for amoxicillin/clavulanate. Of the 197 evaluable patients from whom a susceptible pathogen was recovered, presumptive eradication rates at end of therapy were equivalent: 55 of 65 (84.6%), 54 of 66 (81.8%) and 55 of 66 (83.3%) for cefdinir QD-, cefdinir BID- and amoxicillin/clavulanate-treated patients, respectively. However, presumptive eradication rates for Streptococcus pneumoniae were significantly lower for cefdinir BID (55.2%) than for amoxicillin/clavulanate (89.5%; P = 0.0019) and marginally lower than for cefdinir QD (80%; P = 0.054). Diarrhea was the most common treatment-associated adverse reaction in all groups but was significantly more common in amoxicillin/clavulanate-treated patients (35%) than in patients who had been treated with cefdinir QD (10%, P<0.001) or cefdinir BID (13%, P<0.001). CONCLUSIONS: A 10-day regimen of cefdinir 14 mg/kg QD or 7 mg/kg BID was as clinically effective overall as a 10-day regimen of amoxicillin/ clavulanate 40/10 mg/kg/day divided TID in the treatment of tympanocentesis-confirmed, nonrefractory AOM in children. These data suggest that cefdinir QD may be a better alternative than cefdinir BID for refractory AOM. Both dosing regimens of cefdinir were associated with significantly fewer gastrointestinal adverse reactions than was amoxicillin/clavulanate.
Acute Disease↗
Increasing bacterial resistance in pediatric acute conjunctivitis (1997-1998).
We sought to determine the current level of resistance in Haemophilus influenzae and Streptococcus pneumoniae, the primary pathogens of pediatric conjunctivitis. Between January 1997 and March 1998, we prospectively cultured acute conjunctivitis in 250 ambulatory pediatric patients from rural Kentucky whose average age was 24.3 months. In those 250 cases, 106 H. influenzae (42% of the total) and 75 S. pneumoniae (30% of the total) pathogens were isolated, with no growth or no pathogen resulting in 79 cases (32% of the total). Beta-lactamase was detected in 60 (69%) of 87 tested strains of H. influenzae. Among 65 isolates of S. pneumoniae tested for penicillin susceptibility, 44 (68%) were susceptible, 17 (26%) were resistant, and 4 (6%) were intermediate. Conjunctivitis with acute otitis media was observed in 97 patients (39%), and H. influenzae was recovered in 57% of these 97 cases. As for in vitro activity, ciprofloxacin, ofloxacin, and tetracycline were the most active; and gentamicin, tobramycin, polymyxin B-trimethoprim, and polymyxin B-neomycin were intermediately active. Sulfamethoxazole possessed no activity against either pathogen. Beta-lactamase production was detected in 69% of H. influenzae strains, which still remains the primary causative pathogen of both conjunctivitis and conjunctivitis-otitis syndrome. Penicillin-nonsusceptible S. pneumoniae was observed in 32% of 65 patients with S. pneumoniae conjunctivitis, with most strains being penicillin resistant.
Anti-Bacterial Agents↗
In-vitro activity of levofloxacin against Streptococcus pneumoniae with various levels of penicillin resistance.
This in-vitro study was designed to compare the activity of levofloxacin with that of ciprofloxacin, ofloxacin, erythromycin, penicillin, amoxycillin, loracarbef, cefaclor, cefpodoxime, ceftriaxone, trimethoprim-sulphamethoxazole, clindamycin and vancomycin against a collection of 202 Streptococcus pneumoniae isolates (56% susceptible to penicillin, 34% intermediate, 10% resistant). The isolates (60% nasopharyngeal, 40% middle ear) were obtained from otherwise healthy children at child care centres in urban and rural Nebraska, and at a paediatric clinic in rural Kentucky. MICs were determined by NCCLS agar dilution methodology using an inoculum of 10(4) cfu/spot. Using NCCLS breakpoints, the percentage of penicillin-intermediate and -resistant strains susceptible to the evaluable agents were, respectively, as follows: levofloxacin (99%, 100%), ofloxacin (87%, 100%), erythromycin (52%, 65%), ceftriaxone (93%, 25%), trimethoprim-sulphamethoxazole (7%, 0%), clindamycin (93%, 100%) and vancomycin (100%, 100%). Without NCCLS interpretive criteria, no conclusions could be made concerning the susceptibility of penicillin-intermediate and -resistant strains to the other study drugs. All beta-lactam antibiotics, erythromycin and trimethoprim-sulphamethoxazole were less active against penicillin-resistant strains, indicating that these may be suboptimal agents for empirical therapy for suspected S. pneumoniae infections in these patient populations. However, levofloxacin, ofloxacin, clindamycin and vancomycin were equally active against penicillin-susceptible and -resistant strains. These data suggest that the efficacy of levofloxacin should be examined in both adult and paediatric S. pneumoniae infections involving body sites where levofloxacin concentrations > 2 mg/L can be achieved safely.
Anti-Bacterial Agents↗
Spectral gradient acoustic reflectometry: detection of middle ear effusion in suppurative acute otitis media.
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Acoustic Impedance Tests↗
Adhesin expression in matched nasopharyngeal and middle ear isolates of nontypeable Haemophilus influenzae from children with acute otitis media.
The HMW1 and HMW2 proteins, Hia, and hemagglutinating pili are important adherence factors in nontypeable Haemophilus influenzae. To gain insight into the relative importance of these adhesins in nasopharyngeal colonization and localized respiratory tract disease, we assessed their expression in matched nasopharyngeal and middle ear isolates of nontypeable H. influenzae from 17 children with acute otitis media. In all patients, including 11 with bilateral disease, the matched isolates were isogenic based on total protein profiles and genomic fingerprints. Of the nasopharyngeal isolates, 14 expressed only HMW1/HMW2-like proteins, 1 expressed only Hia, 1 expressed only pili, and 1 expressed both Hia and pili. Further analysis revealed concordance between nasopharyngeal isolates and the matched middle ear isolates for expression of the HMW1/HMW2-like proteins and Hia. In contrast, in the two children whose nasopharynges were colonized by piliated organisms, the corresponding middle ear isolates were nonpiliated and could not be enriched for piliation. Nevertheless, Southern analysis revealed that these two middle ear isolates contained all five hif genes required for pilus biogenesis and had no evidence of major genetic rearrangement. In summary, the vast majority of isolates of nontypeable H. influenzae associated with acute otitis media express HMW1/HMW2-like proteins, with expression present in both the nasopharynx and the middle ear. A smaller fraction of nasopharyngeal isolates express pili, while isogenic strains recovered from the middle ear are often refractory to enrichment for piliation. We speculate that the HMW adhesins and Hia are important at multiple steps in the pathogenesis of otitis media while pili contribute to early colonization and then become dispensable.
Acute Disease↗
Primary pneumococcal peritonitis complicated by exudative pleural effusion in an adolescent girl.
A healthy, young adolescent girl developed primary pneumococcal peritonitis, an infection rarely reported in this age group in North America. Her course was further complicated by exudative pleural effusion and pneumonia despite receiving 10 days of clindamycin therapy. Laparascopy proved useful in making the initial diagnosis, but may have contributed to the pathogenesis of the pulmonary process. Case presentation, management, and etiology are discussed.
Adolescent↗
Attention-deficit disorder. A paradigm for psychotropic medication intervention in pediatrics.
Pediatricians frequently encounter patients with behavioral or academic problems in clinical practice. Assessing and managing these patients requires awareness of the numerous physical, emotional, and psychological causes. Because of their limited contact with these patients during a routine visit, pediatricians as a minimum, should rely on careful parental and social history, teachers' evaluations by checklist, achievement test scores and grades, and the clinicians' own gestalt regarding patients' behavior. This article provides a framework that practitioners can incorporate into their routine office practices. Practitioners must also be knowledgeable about different forms of ADD and learning disabilities, differential diagnosis, and frequently encountered comorbidities. A modest armamentarium of psychotropic drugs potentially useful in the treatment of ADD are available; however, they must be aware of indications, subtle differences in pharmacokinetics, rates of efficacy, and adverse effects for these medications. Appropriate behavioral intervention, educational assessment, and placement when necessary are also essential for optimal management. Enabling the child or adolescent to achieve successfully in school, to experience positive social interactions, and to regain self-esteem are the more rewarding facets of pediatric care.
Adolescent↗
Spectral gradient acoustic reflectometry for the detection of middle ear effusion by pediatricians and parents.
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Acoustic Impedance Tests↗
Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media.
Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most frequently isolated pathogens in patients with acute otitis media (AOM). Other potential causative pathogens include Streptococcus pyogenes in older children and Chlamydia pneumoniae in younger children. The recent emergence of penicillin-resistant S. pneumoniae and the increasing frequency of beta-lactamase-producing strains of M. catarrhalis and H. influenzae are creating concerns regarding the use of amoxicillin as traditional first line empiric therapy for AOM in younger children. Both the in vitro antibiotic activity against these more resistant causative pathogens and the antibiotic concentrations achieved in middle ear fluid must be considered when selecting antibiotics for treatment of refractory AOM. The newer macrolides, azithromycin and clarithromycin, provide reasonable in vitro coverage against penicillin-resistant S. pneumoniae and beta-lactamase-producing H. influenzae, although azithromycin is more active against the latter. Both drugs also achieve notably higher, sustained concentrations in middle ear fluid than do beta-lactam antibiotics. Thus the newer macrolides represent important new rational alternatives for the management of AOM.
Anti-Bacterial Agents↗
Future indications for macrolides.
The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.
Acquired Immunodeficiency Syndrome↗