STREPTOCOCCUS PNEUMONIAE CAUSES OTITIS MEDIA WITH HIGHER FEVER AND MORE REDNESS OF TYMPANIC MEMBRANES THAN HAEMOPHILUS INFLUENZAE OR MORAXELLA CATARRHALIS (1999)

By the time children become 2 years old, approximately two-thirds of them have had one or more attacks of acute otitis media.1, 2 The major bacterial agents associated with this disease include Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. S. pneumoniae is the most common microorganism associated with middle ear infection in children. A significant problem is the increase in antibiotic resistance of this important pathogen to the antibiotics commonly used against it.3 This problem has raised several concerns: (1) when and who should be treated with antibiotics; and (2) when could treatment be safely delayed? Few pediatricians have been trained to perform tympanocentesis. Thus the caregivers are left to statistical probabilities as to which microbe they might be treating. During the past 15 years we have witnessed the rise of M. catarrhalis, a Gram-negative diplococcus, to the third most prevalent cause of acute otitis media, sinusitis and even bronchitis in adults. Almost all strains of M. catarrhalis produce beta-lactamase.4 Its role in respiratory infections is well-supported.5-9 Van Hare et al.10 showed that M. catarrhalis increased from 10% in earlier reported series of otitis media to 17%, either as a single pathogen in 11% of instances or as 6% of copathogens in others. An increased prevalence during the winter season compared with the warmer months of the year was noted. We previously reported recovery of S. pneumoniae from 37% of patients with acute otitis media, H. influenzae from 27% and M. catarrhalis from 25%.3 Realizing that changes in the prevalence of all these strains and their increased resistance to antibiotics, such as penicillin and amoxicillin, presented a major change in the susceptibility of the microbes as well as a practical problem in the therapeutic approach to the condition, we decided to examine, in a comparative fashion, similarities and differences in the subjective and objective findings of patients with acute otitis media caused by S. pneumoniae, M. catarrhalis and H. influenzae. We thought that if we were able to identify clinical differences among the three most important microbial agents associated with acute otitis media with effusion (AOME), we might be able to address the issue of whether there was a possibility through clinical diagnosis of individualizing treatment in otitis media. Methods.Patients. Pediatric patients with acute otitis media, without exposure to antibiotics within the previous week, were enrolled in the trial. These patients were enrolled consecutively by one pediatrician in comparative trials of different antibiotics to treat acute otitis media. The diagnosis of acute otitis media was made on the basis of all three findings: (1) bulging of ear drum(s); (2) decrease/absence of mobility of a tympanic membrane(s); (3) opacification of a tympanic membrane regardless of color. We obtained written informed consent from all participants. Tympanocentesis was performed 20 min after premedication with acetaminophen/codeine syrup. The medication contained 12 mg of codeine, 2.5 mg of valium and 160 mg of acetaminophen per ml. The dosing was calculated on the basis of the codeine component to deliver 1.20 mg of codeine per kg by mouth. A 17-gauge, short-beveled needle connected to a tuberculin syringe was used to obtain middle ear exudate. The temperatures of all patients were recorded by tympanic thermometer before enrollment. The highest recorded temperature in the previous 24 h was used for the calculation purpose of the study. Laboratory methods. Clinical data from each patient were collected in a standard form, which asked for age, sex, symptoms and findings, general data and specific results to the middle ear examination. Culture was done on a chocolate agar plate with an optochin disk and a blood agar plate with a bacitracin disk. H. influenzae isolates were processed by traditional methods in microbiology including Fildes-enriched chocolate agar or Haemophilus test medium. M. catarrhalis was identified by Gram stain and beta-lactamase production, followed by oxidase test (BBL, Cockeysville, MD) and a commercially available M. catarrhalis test (Catarrhalis Test Disc; Remel, Lenexa, KS). S. pneumoniae was identified by checker-appearing or mucoid colonies with alpha-hemolysis on blood agar plate and optochin disk susceptibility. Resistance to penicillin was assessed by an oxacillin (1-mg) disk and by E test strips (AB Biodisk, North America, Piscataway, NJ). Statistical analysis. The groups were compared by entry demographics, middle ear pathogens, subjective findings and physical findings. Differences among groups were examined by chi square analysis or Fisher's exact test. Results. Two hundred twenty-four children participated in the study. Overall we recovered bacterial pathogens from 95% of middle ears. S. pneumoniae was recovered from 85 (38%), H. influenzae from 62 (28%) and M. catarrhalis from 50 (22%). These 3 microbes accounted for the etiology of disease in 88% of patients. In addition Streptococcus pyogenes (4%), Streptococcus aureus (2%) and others including no growth (5%) constituted the remaining 12% (27) of cultures. We were unable to locate those data for (1) 2 patients with S. pneumoniae, (2) 2 patients with H. influenzae and (3) 1 patient with M. catarrhalis. Most patients with the 3 major pathogens were male: S. pneumoniae, 54 of 83 (65%); H. influenzae, 34 of 60 (57%); and M. catarrhalis, 31 of 49 (63%). Their mean (median) ages were 29 months (22), 5 years, 36 months (24) and 30 months (17), respectively. Analysis by age <24 months vs. ≥24 months revealed no differences in age and distribution between those with S. pneumoniae and M. catarrhalis (58% vs. 63%) <24 months of age, whereas for those with H. influenzae only 37% were <24 months of age (Fisher's exact test, P = 0.009). We found no significant differences in the degree of pain, whether mild, moderate or severe, including screaming in pain among those with S. pneumoniae, H. influenzae or M. catarrhalis(Table 1). Significantly, more patients had temperatures ≥37.8°C among those with S. pneumoniae in their middle ear exudates. Fifty percent of patients with S. pneumoniae had temperatures that fit that category. There were no significant differences between H. influenzae and M. catarrhalis in the number of those with temperatures ≥37.8°C, i.e. 27% in the M. catarrhalis vs. 20% of those with H. influenzae. The chi square calculation for those with temperatures >37.8°C was significantly different for those with S. pneumoniae than for the other two pathogens (14.95, P = 5.6 × 10−4). There were significantly more patients with temperatures ≥38.3°C and S. pneumoniae in their middle ears than those with other otitis media pathogens (chi square, 18.9; P = 7.9 × 10−4). We also examined the appearance of the tympanic membrane. Very red bulging tympanic membranes were noted in 47 or 57% of patients with S. pneumoniae, 19 or 31% in those with H. influenzae and 8 or 16% with M. catarrhalis. This difference was statistically significant (chi square, 17.5; P = 1.5 × 10−4).TABLE 1: Subjective findings and corresponding middle ear pathogens To evaluate whether we could utilize physical findings to guide selection of patients with a specific pathogen, we examined those with tympanic membrane findings traditionally considered abnormal (i.e. yellow or red bulging eardrums) and temperatures of ≥38.3°C. Although 33 (41%) of S. pneumoniae patients had yellow or red bulging eardrums with temperatures ≥38.3°C, only 1 patient in each group of those with H. influenzae (1 of 60 or 1.6%) or M. catarrhalis (1 of 49 or 2%) met this criterion. This approach resulted in a sensitivity of 41%, a specificity of 98%, a positive predictive value of 94% and a negative predictive value of 69% for detecting patients with S. pneumoniae acute otitis media. Our analysis did not include those patients with Staphylococcus aureus (who had an indolent presentation), those with no pathogens or patients with group A streptococci. However, if one were to recalculate the analysis on the basis of all 224 tympanocentesis and assume that all patients with group A streptococci were indistinguishable from those with S. pneumoniae in their middle ears, the sensitivity and specificity would still be at 40% and 92%, respectively, but the positive predictive value would drop to 57% and the negative predictive value would be 72%. We subsequently analyzed those with yellow or red bulging eardrum and temperature ≥38.3°C in terms of age group, such as <24 months and ≥24 months and S. pneumoniae. Two (4%) of the 51 patients with H. influenzae or M. catarrhalis who were younger than 24 months of age had these findings vs. 24 of 47 (51%) of those with S. pneumoniae. Such findings for those <24 months of age had a sensitivity of 58%, a specificity of 96%, a positive predictive value of 98% and a negative predictive value of 61% for those with S. pneumoniae. For those ≥24 months of age, respectively, none of the 56 patients with H. influenzae or M. catarrhalis had these findings vs. 9 of 34 (26%) with S. pneumoniae. Thus the sensitivity was 26% and the specificity was 100%, with a positive predictive value of 100% and a negative predictive value of 69%. Discussion. In a previous communication we reported that patients with acute otitis media caused by H. influenzae and M. catarrhalis were indistinguishable in clinical and physical findings.11 However, our experience considering the three major pathogens reveals that, although on the basis of subjective finding we could not differentiate one from the other, significantly more patients with S. pneumoniae had yellow or very red bulging tympanic membranes and temperatures >38.3°C than those with acute otitis media caused by H. influenzae or M. catarrhalis. These two findings coexisted in 40% of patients with acute otitis media caused by S. pneumoniae. The sensitivity and predictive value for these two findings were reassuring as was the positive predicted value. Hence this group of patients could be considered likely to have a significant treatable middle ear pathogen. This finding may support a therapeutic approach with antimicrobials. Although some have advocated withholding antimicrobial therapy12 for AOME, this is not universally accepted. Furthermore there has been an abiding concern about withholding therapy in all patients, particularly in those <2 years of age and in those infected with S. pneumoniae, an organism more likely to result in serious extraotic disease. Therapy of AOME has become a particularly pressing problem because S. pneumoniae has become less sensitive (regardless of dose) to amoxicillin, previously considered the antibiotic of first choice, and to other orally administered antimicrobials. The use of antibiotics that possess better coverage against H. influenzae and M. catarrhalis may be more appropriate for those patients with H. influenzae or M. catarrhalis whose clinical findings are not as suggestive of S. pneumoniae. Patients in our study who had the more classical middle ear presentation that one would expect with a more virulent organism like S. pneumoniae were not limited to any particular age group and, in fact, were equally distributed in the study group with age ranges arranged symmetrically from 6 to 36 months (data not shown). For those ≥24 months of age none had fever ≥38.3°C and a bulging of red/yellow drum (specificity of 100% and a positive predictive value of 100%). The sensitivity of these findings for patients <24 months of age with S. pneumoniae-associated AOME as observed as well as the positive and negative predictive values are also reassuring when considering treatment options. The patients in this study represent ∼10% of the patients diagnosed with otitis media in this practice. (Essentially all of these study patients were diagnosed by one of the authors and represented 90% of those diagnosed by him with AOME in his practice.) William J. Rodriguez, M.D., Ph.D. Richard H. Schwartz, M.D. Department of Pediatric Infectious Diseases and Pediatrics; Children's National Medical Center; Washington, DC (WJR) Inova Hospital for Children; Falls Church, VA (RHS)