In vivo sensitivity test in otitis media: efficacy of antibiotics.

During a 10-year period, antibiotics were assigned in random, double-blind fashion in six combinations to treat 948 episodes of otitis media in children. Exudate from the middle ear of all patients was cultured before treatment. Three follow-up visits were conducted; the first follow-up visit was three to five days after the start of therapy, and the second and third visits were 14 and 31 days after onset of treatment. Exudates were recultured for 75% of the patients on the first follow-up visit. Comparison of treatment results showed that triple sulfonamide combined with either phenoxymethyl penicillin, or benzathine and procaine penicillin G given intramuscularly (IM) was as effective as was ampicillin or amoxicillin. Phenoxymethyl penicillin and cyclacillin alone were usually effective against pneumococci but relatively ineffective against Haemophilus influenzae. Cefaclor and trimethoprim-sulfamethoxazole produced unsatisfactory results in about half the cases caused by pneumococci or H influenzae. Although production of beta-lactamase by some otitis-causing Haemophilus and Staphylococcus species may explain the ineffectiveness of some treatments, the percentage of organisms positive for beta-lactamase was too small to be responsible for the poor results with certain drugs.

Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media.

During a 28-month period, 84 children with acute otitis media were studied by viral and bacterial cultures of middle ear fluid and viral cultures of nasal lavage fluid. Viruses were isolated from the middle ear fluid of 17 (20%) patients. Evidence of viral infection was demonstrated by positive viral cultures of middle ear fluid and/or nasal lavage fluid in 33 (39%) patients. Rhinovirus in one patient and influenza b virus in another were the only pathogens isolated. Influenza virus, enterovirus, and rhinovirus were the most common viruses found in middle ear fluids. Parainfluenza virus, adenovirus, and respiratory syncytial virus were found less often. In 82% of cases, the virus isolated from middle ear fluid was also isolated from nasal lavage fluid, but only 44% of viruses found in nasal lavage fluid were also found in middle ear fluid. Mixed bacterial and combined viral-bacterial infections were common. Only 15% of patients had no pathogen isolated from middle ear fluids. Using tissue culture techniques, we demonstrated that enterovirus and rhinovirus are also common middle ear pathogens. Our data reemphasize the significance of viruses as etiologic agents of acute otitis media and propose several questions regarding the viral-bacterial interactions and the types of viruses involved in the pathogenesis of the disease.

Use of pneumococcal polysaccharide vaccine in preventing otitis media in infants: different results between racial groups.

A total of 133 children between 6 and 11 months of age with at least one episode of otitis media were given one of two pneumococcal vaccines. One vaccine contained 25 microns of types 1, 3, 6, 7, 14, 18, 19, and 23 and the other vaccine (control) contained 25 microns of types 2, 4, 5, 8, 9, 12, and 25. Follow-up care of the 65 black infants revealed significantly more otitis media visits in those infants receiving the control vaccine. Among the 68 white infants there was no difference between control and vaccine groups after vaccination.

Use of C-reactive protein in differentiation between acute bacterial and viral otitis media.

OBJECTIVES: The objectives of this investigation were: (1) to determine degree of elevation of serum C-reactive protein (CRP) in uncomplicated acute otitis media (AOM); (2) to compare serum CRP levels in bacterial and viral otitis media; and (3) to determine whether a single serum CRP level, obtained early in the course of AOM, could be used to differentiate between viral and bacterial otitis media. DESIGN AND METHODS: Sera were obtained from otherwise healthy infants and children with AOM who were 3 months to 7 years of age between 1989 and 1991. Tympanocentesis, bacterial and viral studies of the middle ear fluids, virologic studies of nasal wash specimens, measurements of serum antibody titers to respiratory viruses, blood counts, and quantitation of serum CRP concentrations were performed. After the initial tympanocentesis, an oral antibiotic was given for the next 10 days. The patients were clinically reevaluated over next 4 weeks. OUTCOME MEASURES: Serum CRP concentrations were compared among subjects with AOM who were divided into four groups based on the results of bacteriologic and virologic studies: group I, Bacterial infection (n = 82); group II, bacterial and viral infections (n = 69); group III, viral infection (n = 12); and group IV, no identifiable pathogen (n = 22). RESULTS: There was no statistical difference in serum CRP values among the four groups. The ranges of CRP were less than 0.6 to 22.8, less than 0.6 to 17.8, less than 0.6 to 2.0, and less than 0.6 to 6.8 mg/dL in groups I through IV, respectively. However, when CRP values in bacteria-positive cases were compared with CRP concentrations in bacteria-negative cases (1.58 +/- 3.16 vs 0.64 +/- 1.24 mg/dL), the difference was statistically significant. Furthermore, a significantly higher proportion of bacteria-positive cases had serum CRP concentrations greater than 2 mg/dL, compared with those in bacteria-negative cases. There was no correlation between initial CRP values and clinical findings and/or the clearance of bacteria from the middle ear. After 10 days of antibiotic treatment, CRP values returned to normal (< 0.6 mg/dL) in all cases. CONCLUSION: In AOM, the range of serum CRP varied from less than 0.6 to 22.8 mg/dL. High CRP values (> 2.0 mg/dL) were associated with 22% of cases of bacterial AOM but only with 6% of nonbacterial AOM. High levels of serum CRP were found to be very specific in detecting bacterial AOM, and no cases of viral AOM without a concurrent bacterial infection were found to exhibit high serum levels of CRP.

Pneumococcal polysaccharide immunization in infants and children.

By using indirect hemagglutination, the antibody responses of normal infants and children to an octavalent pneumococcal vaccine that contained pneumococcal polysaccharide types 1, 3, 6, 7, 14, 18, 19, and 23 were evaluated. By 2 years of age, there was a significant rise in hemagglutination titers to all the polysaccharide types, except type 19. By 6 to 8 months of age, five of the eight types of pneumococcal polysaccharides tested resulted in up to 60% responders and, by 2 years, a significant number responded to all pneumococcal polysaccharide types in the vaccine. Pneumococcal polysaccharide type 3 resulted in a significant antibody response as early as 3 months of age, whereas type 19 never resulted in a significant antibody response. Except for type 3, it seemed that when the other pneumococcal polysaccharides tested produced an antibody response, the degree of resonse did not subsequently change significantly with increasing age. The relationship of antibody response to age for pneumococcal polysaccharides is similar to that found for other polysaccharide vaccines. Based on the results of our study, we would recommend immunization with pneumococcal vaccine at 6 months of age with repeat immunization at 2 years of age, especially in high-risk children.

Bacteriologic and clinical efficacy of cefixime compared with amoxicillin in acute otitis media.

The ability of cefixime or amoxicillin to eradicate causative pathogens was evaluated in 140 infants and children with acute otitis media with effusion. When pretherapy and on-therapy bacteriologic cultures were used, success was defined as elimination of pathogens regardless of clinical improvement. Parent compliance with administration instructions was closely monitored. Cefixime was administered daily or twice daily and because results on the two dosage regimens did not differ, data were combined for analysis. Results suggested that cefixime was somewhat more effective than amoxicillin for acute otitis media with effusion caused by Haemophilus influenzae but less effective for infections caused by Streptococcus pneumoniae. The study agents were equally effective against Branhamella catarrhalis.

Immunology and microbiology in acute otitis media.

Various immunological parameters were measured in serum, middle ear fluid (MEF), and lymphocytes from peripheral blood and MEF of infants with acute otitis media due to S. pneumoniae or H. influenzae. Approximately half of 131 patients had IgE specific antibody to the infecting bacterium as determined by the indirect fluorescent antibody (IFA) technique. Seventy-one percent of these IgE positive patients had IgE specific antibody in the MEF. Total IgE concentration was found to be from an average of 1.5 to 3.0 times higher in the MEF when compared to the simultaneously drawn serum. In addition, antibody to pneumococcal capsular polysaccharides and to pneumococcal C-carbohydrate was demonstrated in the MEF by radioimmunoassay. When MEF specific antibody was compared to serum antibody it appeared that antibody to C-carbohydrate was more concentrated in the MEF. That this antibody was of the IgE class was suggested by IFA but not conclusively proven. Evidence exists that conditions for enhanced IgE synthesis is concomitantly associated with a decrease in T-cell activity. T-cell function in MEF derived lymphocytes as determined by rosette formation and by phytohemagglutinin (PHA) stimulation was approximately one-tenth that of the peripheral blood lymphocytes. However, that T-cells may participate in the immune response to polysaccharides was suggested by the observation that polysaccharide stimulated peripheral blood lymphocytes from infants immunized with octavalent pneumococcal capsular vaccine underwent protein synthesis two to three times that of the PHA stimulated cells. The clinical significance of this finding as well as the nature of the cell responsible for the increased protein synthesis remains to be established. It is hypothesized that acute otitis media results from local synthesis of bacteria specific IgE antibody which is enhanced by a paucity of local T-cell activity.

Role of leukotriene B4 and interleukin-8 in acute bacterial and viral otitis media.

In order to evaluate the role of polymorphonuclear leukocytes (PMNs) in acute otitis media (AOM), levels of leukotriene B4 (LTB4), a potent inflammatory product of PMNs, and interleukin-8 (IL-8), a PMN chemotactic cytokine, were measured in 271 middle ear fluid (MEF) samples from 106 children with AOM. Forty-two percent of the patients had evidence of respiratory viral infection. At the time of diagnosis, levels of both LTB4 and IL-8 were higher in the MEFs from patients with AOM associated with bacterial or bacterial and viral infection than those MEFs containing no pathogen (p < .05). Antibiotic treatment was not associated with a significant change in levels of LTB4 or IL-8 in the MEFs obtained 2 to 5 days into treatment, compared to those obtained at diagnosis. Bacteriologic failure after 2 to 5 days of treatment was associated with high LTB4 levels in the initial MEFs (p = .05). Recurrence of AOM within 1 month was associated with high IL-8 levels in the initial MEF (p = .04). Our findings suggest that LTB4 and IL-8 are produced during acute infection of the middle ear, and these PMN-related inflammatory substances may play an important role in delaying recovery or in recurrence of AOM. Effective treatment of AOM may require eradication of bacteria by antibiotics, as well as pharmacologic agents that modulate PMN functions.

Brainstem auditory evoked potentials in young children before and after tympanostomy tube placement.

To evaluate the effect of tympanostomy tube placement upon the hearing function of infants and young children, brainstem auditory evoked potentials (BAEP) were recorded in a group of young children (mean age 22 mos) receiving this treatment for otitis media with effusion (OME). For comparison, a group of healthy infants with normal behavioral audiometry were also tested with BAEP. Hearing loss was estimated for each ear using peak V latency-intensity curves. To evaluate the immediate effect of tube placement, 98 ears in 52 children were tested immediately before and after tube insertion. The 63 ears with effusion had prolonged peak latencies that decreased significantly (P < 0.001) immediately after tube placement and a mean hearing loss estimate of 22 dB that improved significantly (P < 0.0001) to 11 dB immediately after tube insertion. The 35 ears without effusion at myringotomy had a mean hearing loss estimate of 8 dB that did not change significantly after tube insertion. To evaluate the short-term effect of tube presence, 39 ears in 25 children were tested 3 weeks to 18 months after tube insertion. The 28 ears with dry tubes had a mean hearing loss estimate of 3 dB, and the 11 ears with otorrhea had a mean hearing loss estimate of 31 dB. The magnitude of mean hearing loss estimates in these young children with OME and the improvement in hearing function with tube placement is similar to that reported in older children studied with BAEP and audiometry. The study groups with a history of otitis media that had resolved by the time of testing had isolated prolongation of mean III-V interpeak latencies compared to normals (P < 0.01). These studies show that BAEP techniques are useful in estimating hearing loss in children with OME who are difficult to test by behavioral audiometry and show changes in rostral brainstem transmission in very young children with a history of OME.

The effect of early onset of otitis media on educational achievement.

One hundred and forty-four patients from three different pediatric practices were compared using the Science Research Associates (SRA) tests for academic achievement. First, the patients were divided into those who had had three or more attacks of otitis media and those who had had no attacks of otitis media during the first 18 months of life as recorded by their pediatricians. Matched pairs by sex, birth date, occupation of father, school attended and year of testing were made for comparison purposes. Using the one-tailed t-test, a significant difference in the composite score was found favoring the group with no recorded otitis media in the first 18 months of life. All patients were treated with antibiotics.

Does HOME add to the prediction of child intelligence over and above SES?

The most frequently used measure of the educational stimulation provided by the child's home environment is socioeconomic status (SES). Because SES is a global measure, researchers have developed measures that provide more detailed information. One of these is the Home Observation for Measurement of the Environment (HOME), (Caldwell & Bradley, 1984). Our research examined whether HOME adds to the predictability of child intelligence beyond that provided by SES. Subjects were 121 3-year-olds, Black and White, who were administered the fourth edition of the Stanford-Binet and the Peabody Picture Vocabulary Test-Revised. HOME and Hollingshead SES scores were obtained at age 2. HOME added to the predictability of intelligence over and above that provided by SES for the total group of children and for White children but not for Black children. The predictive utility of HOME also depended on the type of intelligence test being used.

Breast feeding and children's intelligence.

Breast feeding was reported in 1992 by Lucas, et al. to provide advantages for the development of intelligence in children of low birth weight, possibly through nutrients or other biological factors found in human breast milk but not cow's milk. Research on breast feeding and intelligence in children of normal birth weight has yielded mixed results, probably because measurement of environmental influences has not been thorough and the range of intelligence components measured has been limited. Our research with 204 3-year-old children of normal birth weight included control measures for the environment and maternal intelligence (Hollings-head socioeconomic status, Home Observation for the Measured Environment, Shipley) and two measures of childhood intelligence (Stanford-Binet Fourth Edition and Peabody Picture Vocabulary Test-Revised). Controlling for environmental variables and maternal intelligence, initiation of breast feeding predicted scores on intelligence tests at age three. Breast feeding was associated with 4.6-point higher mean in children's intelligence.

Assessment of three-year-olds with the Stanford-Binet Fourth Edition.

The Stanford-Binet, Fourth Edition was normed for children 30 months of age and older, but its usefulness with young children (e.g., 36 months) has received little attention. This study of 121 three-year-old children examined possible administration problems, provided correlations with three environmental measures, and compared scores with those of the Peabody Picture Vocabulary Test--Revised. Problems of administration did arise on some subtests, correlations with environmental measures were moderate, and scores on the Stanford-Binet IV and PPVT-R were moderately correlated. The Stanford-Binet IV is a useful test in assessment of a broad range of intellectual abilities.