Information on the epidemiologic, microbiologic, and clinical characteristics of bilateral acute otitis media (BAOM) compared with unilateral AOM (UAOM) is limited. Howie et al1 described 858 instances of AOM in a private pediatric practice during 1965–1968 and reported that unilateral and bilateral ear disease were equally frequent. The mean age in BAOM was 2.4 years while in unilateral disease it was significantly higher (3.3 years for the left ear and 3.5 years for the right ear). Nontypable Haemophilus influenzae represented 26% of all pathogens in BAOM and only 15% in unilateral AOM (UAOM), whereas there was no significant difference for Streptococcus pneumoniae. The authors concluded that their findings confirmed the previous clinical impression of increased bilateral disease in the younger age group.1
We hypothesized that bilateral ear involvement in children is related to a different entity compared with UAOM in terms of microbiology and clinical presentation. The purpose of the present study was to compare the epidemiologic, microbiologic, and clinical characteristics of BAOM with those of UAOM in a large number of children with AOM, enrolled previously in various antibiotic efficacy studies.
MATERIALS AND METHODS
The data were collected from infants and young children aged 3 months to 3 years diagnosed with AOM and enrolled at the Pediatric Emergency Room during 1995–2003 in various antibiotic efficacy studies conducted at the Pediatric Infectious Disease Unit of the Soroka University Medical Center.2–14 The rates of bilateral ear involvement in these studies ranged between 46% and 78%. None of the patients received pneumococcal conjugate vaccine before enrollment to study.
Diagnosis of AOM was made if the patients had: (1) symptoms and physical findings consistent with AOM (symptoms: fever, irritability, and tugging of the ear; signs: redness and bulging of the tympanic membrane with blurring of the anatomic landmarks) and (2) an acute illness for ≤7 days. The signs and the symptoms were evaluated by the same group of 3–4 pediatricians (of them EL and LP evaluated >90% of patients enrolled) and 4–5 otolaryngologists (of them SR and YS examined and performed the tympanocentesis in >80% of patients). Only AOM patients with intact bulging tympanic membranes at enrollment (or purulent otorrhea of <24 hours) were enrolled. Patients with tympanostomy tubes were excluded from the study.
All patients had tympanocentesis performed at enrollment by an otolaryngologist, as previously described.3 Both ears were tapped when bilateral involvement was diagnosed. The middle ear fluid (MEF) samples (0.1–0.2 mL) were immediately aspirated into 1.0-mL sterile tuberculin syringes; part of the fluid was applied onto a sterile swab and sent for bacteriologic culture in transport medium (MW173 Amies medium; Transwab; Medical Wire and Equipment, Potley, UK) for processing within 16 hours at the Clinical Microbiology Laboratory. 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 identification methods used for all pathogens recovered were described elsewhere.3
In patients with bilateral AOM and growth of the same pathogen from both ears, the respective pathogen was counted only once per patient. Mixed infection was diagnosed in those cases where more than 1 pathogen was isolated in a patient irrespectively of growth of the pathogens from only 1 ear or both ears.
A clinical/otologic score (COS) was used at enrollment to determine the severity of the disease. This score was based on the temperature measured in the emergency room, report of irritability by the parents, and the bulging and redness of the tympanic membrane as observed by an experienced otolaryngologist, unaware of the MEF culture results. The categories of irritability, redness, and bulging were classified as absent, mild, moderate, or severe. The maximum score was 12, indicating a temperature of >39°C and presence of severe irritability, redness, and bulging of the tympanic membrane.2 Draining ear with purulent discharge was graded as severe in the category of tympanic membrane bulging. When bilateral disease was present, only the ear with the most severe clinical findings was scored.
Differences in mean scores were tested by Student's t test. Variables implicated in the literature or statistically significant at the level of P < 0.1 in the univariate analysis were included in the multivariate logistic regression models. The final multivariate logistic regression model (including the following variables: age, previous AOM history, MEF culture positivity/negativity, and specific AOM bacterial etiology: H. influenzae or S. pneumonia or mixed infection with these 2 pathogens together) was used to estimate the risk for the BAOM patients (compared with UAOM patients) to present with a high severity COS (≥8). P < 0.05 was considered significant.
A total of 1026 children aged 3–36 months with AOM in whom detailed clinical, otologic, and microbiologic data could be retrieved were enrolled during 1995 through 2003. Of these, 623 (61%) had BAOM.
Sixty-one percent of the patients were <1 year of age and 60% were males (Table 1). The patients with UAOM were older than those with BAOM (mean age, 11.8 ± 6.1 versus 10.6 ± 5.6; P = 0.001) There were no significant differences between UAOM and BAOM patients in respect to gender, ethnicity, and previous AOM history (counted as number of previous AOM episodes and presence or absence of antibiotic treatment during the 48 hours before enrollment).
Positive MEF cultures were recorded in 786 (77%) patients with recovery of 948 pathogens (498 in BAOM and 450 in UAOM). Patients with BAOM had more frequently positive MEF cultures than did patients with UAOM (571 of 623, 83% versus 269 of 403, 67%; P < 0.01). Nontypable H. influenzae, S. pneumoniae, mixed H. influenzae and S. pneumoniae, Moraxella catarrhalis and S. pyogenes, respectively, were isolated in 268 (43%), 111 (18%), 122 (20%), 5 (1%), and 4 (1%), respectively, of the BAOM patients versus 121 (30%), 83 (21%), 49 (12%), 11 (3%), and 3 (1%) of UAOM patients (P < 0.001). Nontypable H. influenzae was more common in BAOM than in UAOM (390 isolates, 63% versus 170 isolates, 42%; P < 0.01). No differences were recorded in the rates of isolation of S. pneumoniae for patients with BAOM and UAOM (233 isolates, 37% versus 132 isolates, 33%; respectively, P = 0.1).
The mean overall COS was 8.1 ± 2.1. The score was significantly higher in patients with BAOM than in those with UAOM (8.3 ± 2.1 versus 7.8 ± 2.1; P < 0.001). The COS was significantly higher in BAOM compared with UAOM when the patients were analyzed according to gender, ethnicity, previous AOM history, and previous antibiotic treatment (Table 2).
COS was higher in culture-positive than in culture-negative AOM (8.2 ± 2.0 versus 7.7 ± 2.2; P < 0.001). The score was higher in culture-positive BAOM than in culture-positive-UAOM patients (8.3 ± 2.0 versus 8.0 ± 2.0; P = 0.03). A similar pattern was observed when each individual pathogen was analyzed (H. influenzae: 8.4 ± 2.0 versus 8.0 ± 2.0, respectively; P = 0.8 and S. pneumoniae: 8.2 ± 2.0 versus 8.0 ± 2.0, respectively; P = 0.5) but the differences did not reach statistical significance for individual pathogens.
Patients with BAOM had more frequently COS ≥8 compared with UAOM patients (371 of 600 evaluable patients, 61.7%, versus 200 of 390 evaluable patients, 51.3%; P = 0.001). Only 8 patients (4 with UAOM and 4 with BAOM) had a COS <4.
The estimated risk for BAOM patients compared with UAOM patients to present with a COS ≥8 was 1.5 (Table 3). In addition, previous history of <3 AOM episodes and a positive MEF culture at AOM diagnosis were found each as independent risk factors for severe disease (COS ≥8). The estimated risk for a BAOM patient with <3 previous AOM episodes and also a culture positive-MEF to present with a COS ≥8 was 2.9 higher than for an UAOM patient with ≥3 previous AOM episodes and culture negative-MEF. Age (both as continuous or age groups), gender, ethnicity, antibiotic treatment during the 48 hours preceding diagnosis, and specific bacterial etiology (H. influenzae versus S. pneumoniae versus mixed infection with these 2 pathogens together) were not found as risk factors for severe AOM (COS ≥8).
The clinical differentiation between a bacterial and a nonbacterial AOM and, more specifically, between S. pneumoniae and H. influenzae AOM may help in choosing an appropriate management for this disease. This includes a possible decision to delay treatment or to choose an appropriate antibiotic if such a treatment is considered necessary.15 In the present study, we showed that BAOM is more frequently diagnosed in young children than UAOM, and more patients with BAOM had positive MEF cultures than did patients with UAOM. In addition, BAOM was caused more frequently by H. influenzae and also associated with higher clinical and otologic severity than was UAOM. We showed in our study, by multivariate analysis, that the presence of bilateral ear involvement in a patient diagnosed with AOM is by itself an additional independent factor increasing the severity of the disease regardless of its pathogens. Furthermore, in a patient with <3 previous AOM episodes, BAOM is strongly associated with disease severity (OR: 2.9 compared with UAOM), particularly in culture-positive patients.
During the last years, immunization against S. pneumoniae with the pneumococcal conjugated vaccines modified etiology of AOM, resulting in an increased likelihood of disease caused by nontypable H. influenzae and M. catarrhalis.16–19 Nontypable H. influenzae is an important pathogen associated with a considerable morbidity20 and its role in AOM and, as shown in the present study, in BAOM occurring at young age, cannot be disregarded.
The American Academy of Pediatrics and the American Academy of Family Physicians define an AOM episode as severe in the presence of moderate to severe otalgia or a temperature of 39°C or higher orally or of 39.5°C rectally.15 These guidelines take into consideration the evidence that more severe AOM episodes are more likely to fail to therapy.21 Recently, Rovers et al22 conducted a meta-analysis of data from 6 randomized studies (1643 children aged 6 months to 12 years) testing the effectiveness of antibiotics in children with AOM and reported that in children <2 years age with BAOM, 55% of controls and 30% of those receiving antibiotics still had pain, fever, or both at 3–7 days, with a rate difference between these groups of −25% and a number-needed-to-treat of 4 children. This subgroup of patients, and also children with both AOM and otorrhea, were found in this study to derive the most beneficial effect from immediate initiation of antibiotic treatment while for the other subgroups of patients, an observational policy seemed justified.22
We did not attempted to establish the true incidence of BAOM compared with UAOM and we are aware that the patients enrolled in this study from the pediatric emergency room presented with a more severe form of disease than that, generally, encountered in the community. Another limitation of our study is related to the clinical scoring system used (based on patient's fever, irritability, and tympanic membrane redness and bulging). As other clinical scores previously used, ours was previously shown to have a limited clinical use due to overlap of clinical symptoms and signs, and therefore a low positive predictive value for the etiology of the disease.23,24
In summary, we showed that: (1) bilateral ear involvement in children with AOM is frequent; (2) nontypable H. influenzae is more frequently involved in the etiology of BAOM than in UAOM; and (3) the clinical picture of BAOM is often more severe than that of UAOM. We suggest that the primary care physicians, at the time of diagnosis, weigh the presence of bilateral ear involvement as an additional severity factor when deciding on the appropriate management of AOM.
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