Spontaneous otorrhea is an uncommon complication of acute otitis media (AOM). The main advantage for the clinician in patients with spontaneous otorrhea resides in the opportunity to obtain cultures of the draining middle ear fluid (MEF) to provide guidelines for therapies directed at specific AOM pathogens.
Brook and Gober1cultured (after cleaning of the external ear canal) otorrhea aspirates in 50 consecutive children with AOM with a new perforation and found bacteria in 51 aspirates obtained from 46 (92%) patients. The authors reported that in otorrhea (compared with nonperforated acutely inflamed ears) the relative importance of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus was higher than that of Haemophilus influenzae and Moraxella catarrhalis. There was no correlation between the organisms isolated and patient age and sex, duration of otorrhea, time of the year, and administration of previous antibiotic therapy.
It is not clear whether the epidemiologic and microbiologic characteristic of AOM presenting as spontaneous otorrhea are similar to those of AOM with intact tympanic membrane who underwent tympanocentesis. Since data on spontaneous otorrhea are limited, we considered that a large-scale study, enrolling hundreds of patients <3 years of age with AOM presenting as spontaneous otorrhea and comparing their epidemiologic and microbiologic characteristics with children with AOM with intact tympanic membrane who underwent tympanocentesis, would be of interest.
The purpose of the present study was to compare the epidemiologic and microbiologic characteristics of AOM presenting as spontaneous otorrhea with AOM with intact tympanic membrane in children who underwent tympanocentesis.
PATIENTS AND METHODS
This study is a retrospective analysis of previous studies conducted during the years 1999 to 2006 and included infants and young children aged 3 to 36 months of age diagnosed with AOM in community clinics or at the Pediatric Emergency Room and from whom a middle ear fluid (MEF) specimen was obtained at diagnosis and cultured at the Microbiology Laboratories of the Soroka University Medical Center, Beer-Sheva. Only patients with clinical signs of AOM of ≤7 days duration were included in the study. Data were not available on patients with culture-negative AOM.
For the patients with positive MEF cultures, the epidemiologic and microbiologic data were further entered in a questionnaire completed at the Pediatric Infectious Diseases Unit and stored into a computerized data base system available at the unit. For each AOM episode, information was collected on patient’s age, gender, ethnicity, laterality of disease, presence of spontaneous otorrhea or AOM with intact tympanic membrane that required tympanocentesis, previous patient history of AOM (number of episodes), number of previous tympanocentesis procedures, and administration of previous antibiotic therapy [recent (last 48 hours) and during 1 and 3 months preceding enrollment].
In patients with spontaneous otorrhea, MEF was collected by direct swab sampling and sent for culture at the Clinical Microbiology Laboratories. In patients who underwent tympanocentesis, prior antisepsis of the ear canal was done with 70% alcohol instilled for 1 minute before the procedure. After the removal of the alcohol by suction, the antero-inferior portion of the tympanic membrane was punctured with a 20-gauge spinal needle. The MEF (0.1–0.2 mL) sample obtained by tympanocentesis was immediately aspirated into a 1.0-mL sterile tuberculin syringe; the fluid was applied onto a sterile swab and sent for culture in transport medium (MW173 Amies medium; Transwab; Medical Wire and Equipment, Potley, UK) for processing within 16 hours at the Clinical Microbiology Laboratories. The swabs with the MEF aspirate were plated on trypticase agar medium containing 5% sheep blood and 5 μg/mL gentamicin and chocolate agar. The plates were incubated aerobically at 35°C for 48 hours. The isolation procedures performed on blood and chocolate agar plates were as previously described.2
S. pneumoniae, nontypable H. influenzae, M. catarrhalis, and S. pyogenes were considered true pathogens causing AOM.
Univariate analysis—differences in various factors analyzed such as age, gender, ethnicity, seasonality, laterality, previous AOM history, previous antibiotic therapy (during the 48 hours preceding enrollment and also during 1 month preceding enrollment), and previous tympanocentesis procedures and distribution of pathogens between the 2 main groups of patients (those with spontaneous otorrhea and those with AOM and tympanocentesis) were tested by Student t test, ANOVA, and χ2 test, as appropriate.
Multivariate regression analysis models adjusting for variables found to be significant for the outcome in the univariate analysis or known to be important (ethnicity) like age, ethnicity, previous antibiotics, AOM history, tympanocentesis history, and pathogens isolated, were used. P < 0.05 was considered significant.
Of 12,617 AOM patients from whom an MEF was obtained, 5247 (42%) were culture-positive patients; spontaneous otorrhea was observed in 822 (15%) patients. There were 55.7% and 57.8% boys among the spontaneous otorrhea and AOM with tympanocentesis patients, respectively; 55.5% and 56%, respectively, were Moslem Bedouins. Mean overall age was 11.27 ± 6.88 months.
Mean age of patients with spontaneous otorrhea was higher than in patients with AOM and intact tympanic membranes who underwent tympanocentesis (15.8 ± 8.2 vs. 9.7 ± 6.7 months, P < 0.01). The percentage of patients with spontaneous otorrhea was lower among children <12 months of age than in patients with AOM and tympanocentesis (304/822, 36.9% vs. 3060/4425, 69.1%, P < 0.001). Among patients aged 12 to 23 months, 44.4% (365/822) and 26.6% (1178/4425) belonged to the spontaneous otorrhea and AOM with tympanocentesis groups, respectively (P < 0.001). Three hundred forty (6.5%) patients were older than 2 years of age: 36% (304/822) and 69.1% (3060/4425) had spontaneous otorrhea and AOM with tympanocentesis, respectively (P < 0.001).
Overall, 25.5% of all patients had received antibiotic therapy during the previous 48 hours, 41.1% presented with their first episode of AOM, and 79.8% underwent tympanocentesis for the first time in life (Table 1). On univariate analysis, more evaluable spontaneous otorrhea patients than evaluable patients with AOM and tympanocentesis had ≥1 previous tympanocentesis procedures (200/792, 25.3% vs. 759/3962, P < 0.001), did not receive antibiotics during the 48 hours preceding the AOM diagnosis (649/786, 82.6% vs. 2951/4043, 73%, P < 0.001), and had ≥1 previous AOM episode (661/808, 81.8% vs. 2216/4079, 54.3%, P < 0.001). No differences were recorded between patients with spontaneous otorrhea and those with AOM and tympanocentesis in terms of gender, ethnicity, seasonal occurrence of AOM, and antibiotic administration during 1 month and 3 months before enrollment.
S. pyogenes was found in higher percentages (47/822, 5.7% vs. 44/4425, 1%, P < 0.001) and H. influenzae (264/822, 32.1% vs. 1805/4425, 40.8%, P < 0.001) and M. catarrhalis (9/822, 1.1% vs. 114/4425, 2.6%, P = 0.01) in lower percentages among spontaneous otorrhea patients than patients with AOM and tympanocentesis. No differences were recorded in the distribution of S. pneumoniae (247/822, 30.1% vs. 1414/4425, 32%, P = 0.3) or mixed infections with S. pneumoniae and H. influenzae (177/822, 21,5% vs. 829/4425, 18.7%, P = 0.07) among the 2 patient groups. Overall, 1107 pathogens were isolated from the MEF of the 822 patients with spontaneous otorrhea and 5551 in the 4425 patients with AOM and tympanocentesis. H. influenzae represented 45% of all pathogens isolated in patients with spontaneous otorrhea and 50% of all pathogens isolated in patients with AOM and tympanocentesis (P < 0.001). S. pyogenes represented 8% of the pathogens isolated in patients with spontaneous otorrhea and only 1% from those with AOM and tympanocentesis (P < 0.001).
In the multivariate model, Bedouin ethnicity (OR: 1.5, 95% CI: 1.2–1.7, P < 0.001), age (OR: 1.1, 95% CI: 1.05–1.10, P < 0.001) for each consecutive month, lack of antibiotic treatment for the 48 hours preceding diagnosis (OR: 2.1, 95% CI: 1.7–2.6, P < 0.001), ≥1 previous AOM episode (OR: 3.2, 95% CI: 2.6–4.0, P < 0.001), ≥1 previous tympanocentesis (OR: 1.4, 95% CI: 1.4–1.7, P = 0.001), and infection with S. pyogenes (OR: 8.2, 95% CI: 5.4–12.3, P < 0.001) were independent risk factors for AOM presenting as spontaneous otorrhea.
In this study, we used an extensive database of prospectively studied, culture-positive episodes of AOM to characterize the epidemiologic and microbiologic characteristics of AOM presenting as spontaneous otorrhea in infants and young children <3 years of age and to compare it with AOM in patients with intact tympanic membrane who underwent tympanocentesis. The study demonstrated that AOM presenting as spontaneous otorrhea in patients <3 years of age is characterized by older age, previous repeated tympanocentesis procedures, recurrent AOM, lack of recent antibiotic treatment, and infection with S. pyogenes.
To ensure maximal reliability of the culture results, Brook et al2 cultured the otorrhea fluid draining from the perforated eardrums of patients with spontaneous otorrhea by needle aspiration through the perforation after previous removal of all the exudate present in the external canal. By culturing both the otorrhea fluid and also the middle ear fluid, the authors reported that 28% of the pathogens present in the MEF would have been missed by culturing the otorrhea fluid alone. In our study, we did not clean the external ear canal before swabbing the otorrhea fluid, but considered as true pathogens in the final calculations only the 4 main agents unquestionably agreed and reported as AOM pathogens (S. pneumoniae, nontypable H. influenzae, M. catarrhalis, and S. pyogenes). Of these pathogens, the presence of S. pneumoniae and H. influenzae, at least, was shown to be almost certainly indicative of the organisms’ presence in the middle ear.1,3,4 We did not report data on the presence of Staphylococccus or Pseudomonas spp. in the cultures obtained either from spontaneous otorrhea or from AOM with tympanocentesis patients, since we considered them to be contaminants originating from skin or external ear canal.
We found that S. pyogenes was isolated in significantly higher percentages in patients with spontaneous otorrhea than in those with AOM with intact tympanic membranes who underwent tympanocentesis. Our data confirm previous data of Brook et al2 who isolated S. pyogenes in 11% of patients with spontaneous otorrhea compared with only 2% to 3% in patients with AOM and unperforated eardrum. Although it was frequently isolated in the MEF of AOM patients during the first half of the 20th century, its importance as an etiologic agent of AOM decreased during recent decades and it is presently ranked as the 4th pathogen (<5% of all cases) causing the disease.5–7 On the other hand, extensive evidence has been accumulated recently supporting the increased local aggressiveness of S. pyogenes (compared with the other 3 pathogens causing AOM). Segal et al8 recently analyzed the role of S. pyogenes in 350 infants and young children with AOM during the period 1999 to 2003 and reported an older age at presentation and higher local aggressiveness (manifested by tympanic perforation and mastoiditis) compared with AOM caused by S. pneumoniae, nontypable H. influenzae or M. catarrhalis. The risk of mastoiditis was 11.6 episodes per 1000 episodes of S. pyogenes–AOM compared with 2.2, 0.3, and 0 episodes of mastoiditis caused by S. pneumoniae, H. influenzae, and M. catarrhalis, respectively. The important role of S. pyogenes in the etiology of acute mastoiditis despite its minor role as a causative agent of AOM was also outlined in other series.9–11 Katz et al11 reviewed all 116 cases of acute mastoiditis hospitalized in a tertiary-care hospital in southern Israel and found that S. pyogenes was the etiologic agent in 26% of cases, second only to S. pneumoniae (33%), while the same pathogen was detected in the same area in the etiology of AOM in only 1% to 2% of cases.2,6,7
H. influenzae and M. catarrhalis were found in lower percentages among spontaneous otorrhea patients than patients with AOM and intact tympanic membrane who required tympanocentesis and these findings are in accord with previously reported data.12–17 Although generally recognized as a less virulent pathogen than S. pneumoniae in the pathogenesis of AOM, persisting less in the MEF of untreated or inappropriately treated AOM patients and being less associated with high fever and severe redness and bulging of the tympanic membrane, H. influenzae is probably impossible to distinguish on a clinical basis form other etiologic agents of AOM.12–15 In experimental otitis media in rats, histopathologic changes in the middle ear and Eustachian tube were mildest with M. catarrhalis infection when compared with other pathogens.16,17
The additional statistically significant findings reported here showed that spontaneous otorrhea occurring in patients younger than 3 years of age has a tendency to appear at an older age and in patients with a more severe previous history in terms of more AOM episodes and need for more tympanocentesis procedures in the past. We also found that lack of antibiotic treatment during the previous 48 days was an additional contributory factor to occurrence of perforation in cases with AOM.
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