Lifetime use of alternative therapy: a study of Florida residents

OBJECTIVE: To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children. METHODS: In a prospective study 92 patients ages 3 to 36 months (median, 11 months) with culture-proved nonresponsive acute otitis media were studied from January, 1995, through August, 1997. The patients were treated with intramuscular ceftriaxone (50 mg/kg/l/day) for 3 days. Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment (Day 1); a second tap was performed on Days 4 to 10. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive culture on Days 4 to 10. Patients were followed until Day 17+/-2. Susceptibility was measured by E test. RESULTS: The main drugs administered before enrollment were amoxicillin (38%), amoxicillinclavulanate (25%) and cefaclor (20%). Organisms recovered (n=105) were: Haemophilus influenzae, 54; Streptococcus pneumoniae, 47; Moraxella catarrhalis, 2; and Streptococcus pyogenes, 2. Thirty-four (72%) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin (MIC 0.1 to 1.0 microg/ml), but all were susceptible to ceftriaxone (MIC < 0.5 microg/ml). Bacteriologic eradication was achieved in 100 of 105 (95%) cases: 54 of 54 (10O%) H. influenzae, 43 of 47 (92%) S. pneumoniae, 1 of 2 (50%) M. catarrhalis and 2 of 2 (100%) S. pyogenes. Bacteriologic success (with no relapse) occurred in 13 of 13 (100%) penicillin-susceptible S. pneumoniae vs. 28 of 34 (82%) S. pneumoniae intermediately resistant to penicillin (4 cases of bacteriologic failure and 2 cases of relapse). CONCLUSION: A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media. The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined.     

Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics

Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the predominant bacteria associated with otitis media. A cohort of 306 infants was followed from birth through 12 months to determine frequency and duration of colonization and risk of acute otitis media (AOM) and otitis media with effusion (OME). M. catarrhalis was the most common bacterium isolated. Infants colonized at < or = 3 months of age were at increased risk of AOM and OME. Early colonization with M. catarrhalis revealed the greatest risk (relative risk [RR] = 1.24), especially for OME (RR = 1.57). There was a strong relationship between the frequency of colonization and OM (r = .37, P < .001,) for each pathogen. Although S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis are part of the normal nasopharyngeal flora during infancy, an increased rate of colonization may identify a subpopulation of children that is at increased risk of OM.     

Pharmacokinetics and pharmacodynamics of new and old antimicrobial agents for acute otitis media

Selection of appropriate antibiotic treatment for children with acute otitis media (AOM) is challenging. Although the diagnosis is relatively easy for experienced clinicians, the distinction between AOM and otitis media with effusion is often more subtle. In general therapy is empiric and the pathogen causing disease in a given patient remains unknown. However, this situation is made even more difficult by the dynamic nature of the pathogenesis of AOM. Both the proportion of patients infected with one of the three primary pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and the antimicrobial susceptibility patterns of these pathogens are changing. Currently there are 16 antibiotics labeled for use in AOM. Only 2 are reliably effective against penicillin-resistant pneumococcus: high dose amoxicillin (80 to 100 mg/kg/day) and im ceftriaxone. Among the others all are beta-lactamase-stable and have proven clinical effectiveness in AOM patients infected with H. influenzae or M. catarrhalis. Even with the high spontaneous resolution rate reported for AOM, antimicrobial therapy remains the standard of care in the United States. Recognition of the fundamental determinants of effective therapy should permit rational antibiotic selection for each patient.     

Surgical treatment for duodenal involvement in Crohn''s disease: report of a case

BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.     

Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media

The management of acute otitis media is complicated by the emergence of resistance to beta-lactam and other antibiotics among common pathogens. We conducted a large, international study of infants and children with acute otitis media to identify pathogens and susceptibility patterns. During the winter of 1994 to 1995, middle ear fluid samples were collected from 917 patients with acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia, Israel, and the United States. A single reference laboratory performed in vitro susceptibility testing. Pathogens were isolated from 62% of the patients. For Streptococcus pneumoniae (30% of the patients), untypeable Haemophilus influenzae (17%), and Moraxella catarrhalis (4%), there was significant variation among geographic regions (P < 0.001). The composite susceptibilities of these three organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate ranged from 90% in Israel to 95% in Eastern and Central Europe. beta-Lactamase was produced by 31 and 100% of the isolates of H. influenzae and M. catarrhalis, respectively. More isolates of S. pneumoniae were susceptible to amoxicillin (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%; P = 0.002). The prevalence of resistant S. pneumoniae was highest in patients less than 12 months of age. S. pneumoniae, H. influenzae, and M. catarrhalis remain the most important bacterial pathogens in patients with acute otitis media; however, their prevalence is variable and resistance patterns are changing.     

Regulation of tissue plasminogen activator production in cultured human fetal mesangial cells

This study was designed to determine the persistence of culturable bacteria versus DNA in the presence of a middle ear effusion in a chinchilla model of otitis media. Cohorts of animals were either infected with an ampicillin-resistant Haemophilus influenzae strain or injected with a tripartite inoculum consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella catarrhalis; and DNA from H influenzae. The H influenzae-infected animals displayed culture positivity and polymerase chain reaction positivity through day 35. In the chinchillas infected with the low-copy number inocula of S pneumoniae, DNA was not detectable after day 1 from the co-inoculated pasteurized M catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA from the live low-copy number bacteria persisted through day 21 even though they were not culture-positive past day 3. These results demonstrate that DNA, and DNA from intact but nonviable bacteria, does not persist in an amplifiable form for more than a day in the presence of an effusion; however, live bacteria, while not culturable, persist in a viable state for weeks.     

The microbiology of secretory otitis

The AA. realize a comparative study on the differences between the nasopharyngeal microbial flora of 50 children suffering a secretory otitis and other 40 children without middle ear disease. In nasopharyngeal cultures the pathogenic flora (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Streptococcus beta hemoliticus group A, Staphilococcus aureus) amounted for 96 percent in children with secretory otitis, which figure was reduced to 80 percent in healthy infants (p < 0.05). Haemophilus influenzae was the most identified microorganism in a both nasopharyngeal and otic flora. We have found a significative association (p < 0.001) among nasopharyngeal and otic flora of each individual.     

Epidemiology of otitis media with effusion in children

The recently accepted international classification for otitis media was applied to a study population of 898 children less than 12 years of age having otitis media with effusion persisting at least three months. Mucoid effusion was aspirated from 48% of ears, was found more often in younger than older patients, was more often bilateral, and was a more stable state during longitudinal observation than was serous otitis media or purulent otitis media (POM). Serous otitis media occurred in only 10% of ears, but was found more often than in younger patients; POM was found in only 7% of ears. Otoscopy did not distinguish among the three effusion types. Known middle-ear pathogens were cultured more often behind red and bulging tympanic membranes from these cases of chronic effusion than behind membranes lacking these characteristics. These observations provide an epidemiologic and clinical base for further investigations of these otitis media types.     

Evaluation of cefaclor in acute otitis media caused by ampicillin-resistant H. influenzae

Cefaclor was used to treat 13 children with acute otitis media caused by ampicillin-resistant strains of Hemophilus influenzae. The children were re-examined on days 4, 10, and 28. Pharmacologic compliance was assessed by means of a bioinhibition assay on a urine specimen obtained on days 4, 7, and 10. Nine of the 13 children had evidence by tympanogram of residual otitis media with effusion (secretory otitis media). Of these, three were noted to have a bulging, yellow or grey eardrum, which suggested an ongoing acute process. A second middle ear culture was obtained from two of the 3 children, but no pathogens were recovered. Two others had recurrence of otitis shortly after cessation of therapy. Cefaclor is an acceptable antibiotic for the treatment of ampicillin-resistant acute otitis media; but, after cefaclor therapy, some children continued to have a bulging eardrum and sterile pus in the middle ear or had recurrences of otitis soon after cessation of therapy.     

Pathogens isolated during treatment failures in otitis

OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure. METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid. RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14. CONCLUSIONS: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.     

Experimental assessment of adaptive possibilities after chronic prenatal exposure to gamma irradiation at various absorbed doses

We measured the levels of serum IgG antibodies to CD outer membrane protein of Moraxella catarrhalis, P6 outer membrane protein of non-typeable Haemophilus influenzae and capsular polysaccharides of Streptococcus pneumoniae in 168 children with otitis media with effusion (OME) who were followed prospectively, using ELISA. Serum IgG antibodies to CD, P6 and pneumococcal capsular polysaccharides were detected in all samples. The anti-pneumococcal polysaccharides antibody level was highest, followed by the anti-P6 antibody level and anti-CD antibody was lowest (median:interquartile ranges were 45.9:19.1-100 microg/ml, 15.6:9.70-23.2 microg/ml and 1.06:0.73-1.87 microg/ml, respectively). In children aged 0-6 years, there were positive correlations among the antibody levels (anti-CD vs anti-P6, r=0.325, p <0.001; anti-CD vs anti-polysaccharide, r=0.397, p <0.0001; anti-P6 vs anti-polysaccharide, r=0.175, p=0.057). However, no relationship was seen in children aged 7-15 years. Children were classified according to severity of OME during the 1-year follow-up. In children aged 0-6 years, the severity of OME correlated inversely with the levels of anti-CD antibody (r=-.23, p=0.012), of anti-P6 antibody (r=-0.292, p=0.0015), and of anti-pneumococcal polysaccharides antibody (r=-0.25, p=0.0064). However, no correlation was found between antibody levels and severity of OME in children aged 7-15 years. These data suggest that persistence and/or recurrence of OME may be due to an insufficient serum antibody response to middle ear pathogens in young children.     

The antibiotic treatment of acute otitis media and sinusitis in children

The development of resistance among the bacterial pathogens causing acute otitis media and sinusitis in children is causing considerable concern. Although normally a mild infection, acute otitis media can produce serious complications with sequelae that can have long-lasting effects. High levels of resistance are now being seen in the three principal pathogens. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Most clinical trials comparing the efficacy of different antibiotics have failed to show differences in clinical efficacy. To overcome this problem, alternative methods of assessing antibiotics have been developed including the "in-vivo sensitivity test" proposed by Howie and retrospective analyses of treatment failures. The treatment of sinusitis is complicated by the difficulty in establishing a clear differential diagnosis. To date, no definitive trials of bacteriologic efficacy in children have been published.     

Penicillium marneffei fungemia in an AIDS patient: the first case report in Taiwan

The microbiology of in 55 ear aspirates obtained from 34 children with chronic otorrhea was studied. Aspiration of the middle ear exudate was done immediately following removal of tympanostomy tube (TT). The middle ear aspirates and swab specimens of the external auditory canals were cultured for aerobic and anaerobic bacteria. Sixty-five isolates were recovered only from the middle ears, 73 only from the external ear canals, and 73 were present at both sites. Analysis of the 138 middle ear isolates demonstrated the recovery of aerobic bacteria only in 28 patients (50%), anaerobes only in seven (13%), and both aerobes and anaerobes in 20 (36%). There were 77 aerobic and 61 anaerobic isolates. Commonly recovered aerobes were Pseudomonas aeruginosa (17 isolates), Staphylococcus aureus (11), Proteus sp. (7), Moraxella catarrhalis (6), Klebsiella pneumoniae (5) and non-typable Haemophilus influenzae (5). Commonly isolated anaerobes were Peptostreptococcus sp. (25 isolates), Prevotella sp. (10), Bacteroides sp. (8) and Fusobacterium sp. (6). Pseudomonas aeruginosa and S. aureus were more often isolated in children older then 6 years. These findings demonstrate the polymicrobial bacteriology of TT-related otorrhea in children. Specimens collected from the external auditory canals can be misleading. Reliable information can be obtained from the ear exudes when collected through the TT or through the open perforation after their removal.     

Methodical aspects of pneumatic segment plethysmography. III. Measuring tourniquet problems

A retrospective study was made of 200 chronic otitis media patients. Simple chronic otitis media was observed in 76 per cent of cases; the rest were associated with cholesteatoma. In about one third of the patients, the contralateral ear showed some inflammatory middle ear disease as well. The average time lapse between initial symptoms and hospitalization was about 10 years. The events leading to the tympanic perforation were difficult to ascertain, but included probably acute otitis media, possibly external otitis, trauma, and a rather large group (35-40 per cent) of insidious 'essential perforations'. The aetiology of the 'essential perforations' is so far not known, but might be non-inflammatory in nature but related to insufficient middle ear aeration and hypo-pneumatization as well as to what is termed atelectatic ears. The bacteria isolated from chronic otitis media ears (usually gram negative bacteria and staphylococcus aureus) are usually not the types of micro-organisms found in association with any primary or acute otitis media. It is proposed that the bacterial infection encountered in what is termed 'chronic otitis media' is often a secondary infection of a primary perforated tympanic membrane, the perforation originating or persisting in underventilated ears, and having arisen from various causes--some of them as yet unknown.     

Gammadelta T cell receptor repertoire in middle ear effusions in children

In order to elucidate the immune response in otitis media with effusion, polymerase chain reaction was employed to examine gammadelta T cell receptor repertoire in the middle ear effusions of patients with otitis media with effusion. RNAs were extracted from 13 middle ear effusions of 10 children with otitis media with effusion. Vgamma2 was the most frequently used Vgamma gene. As for Vdelta gene usage, Vdelta2 amplification gave the strongest signal in 10 out of 13 samples. The results suggest that gammadelta T cells bearing Vgamma2/Vdelta2 T cell receptors accumulate in the middle ear effusions in children, and that these T cells may respond to certain bacteria or bacterial products in the middle ear.     

Nasopharyngeal colonization in Costa Rican children during the first year of life

BACKGROUND: The establishment of the nasopharyngeal flora was followed in Costa Rican children from birth to 1 year of age. METHODS: Nasopharyngeal cultures were obtained at 1 (n = 413), 3 (n = 393), 6 (n = 376) and 12 months (n = 356) of age from children representative of the population in the Puriscal district. Weekly cultures were obtained from a subcohort of these children (n = 101). Mother-infant diads (n = 95) and preschool children (n = 208) attending day-care centers were also studied. RESULTS: The estimated proportion of colonized children in the population differed markedly depending on the frequency of culture. Quarterly cultures showed a slow increase in carrier rates from 3.9% for Haemophilus influenzae, 3.1% for Streptococcus pneumoniae and 6.5% for Moraxella catarrhalis at 1 month of age to 10.1% carrying H. influenzae and 19.4% carrying S. pneumoniae by the end of the first year. By quarterly culture the proportion of children colonized at least once was 36% for S. pneumoniae, 26% for H. influenzae and 28% for M. catarrhalis. In contrast weekly sampling showed that 95 to 100% of the children were colonized at least once during the first year of life with H. influenzae, S. pneumoniae or M. catarrhalis. Nasopharyngeal carriage of H. influenzae, S. pneumoniae and M. catarrhalis was low in the mothers, and very few mother-infant pairs carried identical bacteria at the same time. In contrast carrier rates were high in the siblings attending day care (H. influenzae 27.9%, S. pneumoniae 39.4%, both organisms 26.6%). Infants with siblings had significantly higher bacterial carriage at all ages than infants without siblings. CONCLUSIONS: Quarterly nasopharyngeal cultures showed that Costa Rican infants acquire their nasopharyngeal flora at a rate comparable with that for infants in developed countries and that siblings are an important source of the bacteria. Weekly samplings showed that virtually all children were colonized at least once during the first year of life.     

Repeatability of treadmill exercise ejection fraction and wall motion using technetium 99m-labeled sestamibi first-pass radionuclide ventriculography

Bacterial antibodies were studied in acute, intermediate and convalescent phase sera (mean duration from first to last sample 36 days) of 121 children hospitalized for acute lower respiratory tract infection. Antibody responses were observed in 45% of all cases and in 29% of the 21 children < 1 year old. A total of 15 responses to Streptococcus pneumoniae (pneumolysin), 20 to Haemophilus influenzae, 9 to Moraxella catarrhalis, 3 to chlamydiae and 8 to Mycoplasma pneumoniae were found. In 79 patients with 4 consecutive samples available, 52% of the 31 responses were measurable within 5 days from admission. Overall the responses were not associated with upper respiratory tract bacterial findings or acute otitis media. Significantly more responses were found in the 121 children with acute lower respiratory tract infection than in healthy controls (P < 0.007). We conclude that bacterial antibody assays provide a useful tool in the study of the etiology of acute lower respiratory tract infection in young children, even if the interval between paired serum samples is short.     

Local impairment of immunoreactivity in HIV-infected women with HPV-related squamous intraepithelial lesions of the cervix

The effect on the nasopharyngeal bacterial flora of therapy for 10 days with co-amoxiclav or cefprozil was studied in 50 children with acute otitis media. Before therapy, potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) were isolated in 14 (56%) of those treated with co-amoxiclav and 15 (60%) of those treated with cefprozil. Following therapy, the reduction in the number of these pathogens was the same in the two groups. However, differences between the groups were noted in the recovery of organisms with interfering capability, namely alpha-haemolytic streptococci, Peptostreptococcus anaerobius and Prevotella melaninogenica. Fifty interfering organisms were recovered from each group before therapy. After therapy with co-amoxiclav or cefprozil their number declined to 11 and 42, respectively (P< 0.001).     

Clocks regulating developmental processes

The goal of this study was to investigate the role of chronic otitis media with effusion as a cause of childhood imbalance. Nineteen 4- to 6-year-old children with chronic otitis media with effusion and 14 matched control children underwent a series of laboratory tests, including two standardized tests of balance and locomotion: the Peabody Developmental Motor Scales (PDMS) and the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). The children in the chronic otitis media with effusion group underwent tympanostomy tube insertion. Both groups underwent the same battery of tests within 6 to 8 weeks of initial testing. Analysis of variance for the PDMS and BOTMP demonstrated significantly lower performance in the balance subscales for the otitis group before (P < .01). Both otitis and control groups improved when retested. The improvement was greater and approaching significance in the otitis group on the PDMS and BOTMP (P = .056 and .097, respectively). It is concluded that chronic otitis media with effusion significantly affects balance and coordination skills in 4- to 6-year-old children. These skills improve after tympanostomy tube insertion at a rate greater than that of the control group.     

Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson''s disease

Middle ear effusion has been considered the most common cause of vestibular disturbance in children. However, there have been only a few studies on vestibular disturbance in children with otitis media with effusion. We studied the vestibular systems of 30 children with otitis media with effusion aged 8 to 13 years and compared the results with 15 age- and sex-matched controls. A questionnaire relating to vestibular disturbance was given to patients and their parents. Spontaneous nystagmus and positional nystagmus were recorded by electronystagmography as diagnostic tests of the vestibular system. Romberg's and past-pointing tests were performed on children with otitis media with effusion and controls. After vestibular tests were completed, myringotomy was performed, and a ventilation tube was inserted. The questionnaire and the vestibular tests were repeated after the operation and during the first month after surgery. Our study showed that there was a history of vestibular disturbance in 33% of children with otitis media with effusion. Electronystagmography and Romberg's test findings demonstrated that 33% of the children had vestibular dysfunction (p < 0.05). After myringotomy with ventilation tube insertion, vestibular test results returned to normal, and symptoms related to vestibular disturbance improved. These findings confirm the assumption that middle ear effusion may affect the vestibular system, which can be resolved after myringotomy with ventilation tube insertion.