Miia K. Laine

A Placebo-Controlled Trial of Antimicrobial Treatment for Acute Otitis Media

BACKGROUND The efficacy of antimicrobial treatment in children with acute otitis media remains controversial. METHODS In this randomized, double-blind trial, children 6 to 35 months of age with acute otitis media, diagnosed with the use of strict criteria, received amoxicillin-clavulanate (161 children) or placebo (158 children) for 7 days. The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8. The definition of treatment failure was based on the overall condition of the child (including adverse events) and otoscopic signs of acute otitis media. RESULTS Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P<0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin-clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P<0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin-clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin-clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P<0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04). CONCLUSIONS Children with acute otitis media benefit from antimicrobial treatment as compared with placebo, although they have more side effects. Future studies should identify patients who may derive the greatest benefit, in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance. (Funded by the Foundation for Paediatric Research and others; ClinicalTrials.gov number, NCT00299455.).

Symptoms or Symptom-Based Scores Cannot Predict Acute Otitis Media at Otitis-Prone Age

OBJECTIVE: Acute symptoms are used to diagnose and manage acute otitis media (AOM). We studied whether AOM could be predicted by the reason for parental suspicion of AOM or by the occurrence, duration, and/or severity of symptoms. We also compared scores including or excluding tympanic-membrane examination of children with and without AOM. PATIENTS AND METHODS: Children aged 6 to 35 months with parental suspicion of AOM were eligible. Before tympanic-membrane examination, we registered on a structured questionnaire the reason for parental suspicion of AOM, symptoms, and score components. RESULTS: Of 469 children studied, 237 had AOM and 232 had respiratory tract infection without AOM. The most common reason for parental suspicion of AOM, restless sleep, was not predictive for AOM (RR: 1.0 [95% CI: 0.8–1.2]), nor was ear-rubbing (relative risk [RR]: 0.7 [95% confidence interval (CI): 0.5–1.0]). Neither the occurrence of fever (RR: 1.2 [95% CI: 1.0–1.4]) nor the highest mean temperature within 24 hours predicted AOM, nor did the occurrences of ear-related, nonspecific, respiratory, or gastrointestinal symptoms. The duration and severity of symptoms were not predictive for AOM, although rhinitis lasted longer and conjunctivitis was more severe in children with AOM. The clinical/otologic score (median: 4.0 vs 2.0; P = .000) and the AOM total-severity index (11.0 vs 6.0; P = .000), both including symptoms and tympanic-membrane examination, were higher in those with AOM. The AOM severity-of-symptom scale, based solely on symptoms, was equal in children with and without AOM (6.0 vs 6.0; P = .917). CONCLUSIONS: AOM cannot be predicted by the occurrence, duration, or severity of symptoms at otitis-prone age. Likewise, solely symptom-based scores do not differentiate between respiratory tract infections with or without AOM. Thus, tympanic-membrane examination is crucial in the diagnosis and severity classification of AOM in clinical practice and research settings.

Tympanometry in discrimination of otoscopic diagnoses in young ambulatory children.

Background: Tympanometry can indicate middle ear effusion in children referred for tympanostomy tube placement. In outpatient setting, objective adjunctive tools are needed to diagnose the otitis media spectrum. Methods: We enrolled and followed 515 children aged 6–35 months at primary care level. We compared tympanometry with pneumatic otoscopy and evaluated the proportions of type A, C1, C2, Cs and B tympanograms in relation to specific otoscopic diagnoses in 2206 and 1006 examinations at symptomatic and asymptomatic visits, respectively. Results: At symptomatic visits, different peaked tympanograms were associated with a healthy middle ear as follows: type A in 78%, type C1 in 62%, type C2 in 54% and type Cs in 18% of examinations. In contrast, any peaked tympanogram was related to healthy middle ear in 67% of examinations. Flat (type B) tympanogram was related to otitis media with effusion in 44% and to acute otitis media in 56% of examinations, respectively. At asymptomatic visits, the peaked tympanograms together were associated with a healthy middle ear in 87% of otoscopic examinations. Flat tympanogram indicated otitis media with effusion as well in 87% of examinations. Conclusions: Tympanometry is not a useful tool in detecting specific otoscopic diagnoses because it cannot distinguish between otitis media with effusion and acute otitis media. However, among outpatients all peaked tympanograms suggest a healthy middle ear and a flat tympanogram is useful in detecting any middle ear effusion. Thus, tympanometry can be used as an adjunctive tool, but accurate diagnosis requires careful pneumatic otoscopy.

Acoustic reflectometry in discrimination of otoscopic diagnoses in young ambulatory children.

Background: Studies concerning spectral gradient acoustic reflectometry (SG-AR) have analyzed middle ear effusion only as 1 entity. The usefulness of SG-AR to detect specific otoscopic diagnoses of otitis media in young children is unknown. Methods: Among 515 children aged 6–35 months, we compared SG-AR with pneumatic otoscopy and evaluated the proportions of 5 manufacturer-recommended SG-AR levels in relation to specific otoscopic diagnoses in 2802 and 1240 examinations at symptomatic and asymptomatic visits, respectively. Results: At symptomatic visits, when the angle value was >95° (level 1), healthy middle ear was diagnosed in 76% of otoscopic examinations and acute otitis media in 5%. Levels 2 (70–95°) and 3 (60–69°) did not relate to any otoscopic diagnosis. Levels 4 and 5 associated with acute otitis media in 50% and 64%, and otitis media with effusion in 33% and 32% of examinations, respectively. At asymptomatic visits, levels 1, 2 and 3 were associated with healthy middle ear in 87%, 71% and 54% of examinations, respectively. With levels 4 and 5, otitis media with effusion was diagnosed in 62% and 79% of examinations, respectively. Conclusions: SG-AR is not useful in making specific otoscopic diagnoses. Although the extremities of 5 SG-AR levels are able to differentiate ears with and without effusion, SG-AR is not able to differentiate acute otitis media from otitis media with effusion. Therefore, SG-AR can aid in diagnostics, but careful pneumatic otoscopy is needed to determine accurate diagnoses.

Delayed versus immediate antimicrobial treatment for acute otitis media.

Background: Watchful waiting with the option of delayed antimicrobial treatment for acute otitis media is recommended in several guidelines. Our aim was to study whether delayed, as compared with immediate, initiation of antimicrobial treatment worsens the recovery from acute otitis media in young children. Methods: Children (6–35 months) with acute otitis media received either delayed or immediate antimicrobial treatment with amoxicillin-clavulanate for 7 days. The delayed antimicrobial treatment group (n = 53) consisted of placebo recipients from a randomized-controlled trial to whom antimicrobial treatment was initiated after a watchful waiting period. The immediate antimicrobial treatment group (n = 161) consisted of children allocated to receive antimicrobial treatment immediately. Results: Improvement during antimicrobial treatment (which includes both symptoms and otoscopic signs) was observed in 91% and 96% of children in the delayed and immediate antimicrobial treatment groups, respectively (P = 0.15). Median watchful waiting period was 48 hours. Delayed initiation of antimicrobial treatment was associated with prolonged resolution of fever, ear pain, poor appetite and decreased activity, but not ear rubbing, irritability, restless sleep or excessive crying. Parents of children in the delayed antimicrobial treatment group missed more work days (mean 2.1 versus 1.2 days, P = 0.03). Diarrhea, vomiting and rash were equally common in both groups. Conclusions: Our results indicate that delayed initiation of antimicrobial treatment does not worsen the recovery from acute otitis media, as measured by improvement during treatment. However, watchful waiting before the initiation of delayed antimicrobial treatment might be associated with transient worsening of a child’s condition, prolongation of symptoms and economic losses.

Role of Nasopharyngeal Bacteria and Respiratory Viruses in Acute Symptoms of Young Children.

Background: The spectrum of acute symptoms in young outpatient children with respiratory tract infection (RTI) is variable, and it cannot be explained by the diagnosis of acute otitis media (AOM) versus uncomplicated RTI. We studied that the variation of symptoms is explained by the nasopharyngeal bacteria and/or respiratory viruses. Methods: Children aged 6–35 months with acute symptoms with AOM (n = 201) or without AOM (n = 225) were eligible in this cross-sectional study. We analyzed their nasopharyngeal samples for pathogenic bacteria by culture and for respiratory viruses by polymerase chain reaction. We surveyed 17 symptoms (fever, respiratory, ear related, nonspecific, gastrointestinal) with a structured questionnaire. Results: Fever had a positive association with influenza viruses [odds ratio (OR): 6.61; 95% confidence interval (CI): 1.66–26.27], human metapneumovirus (OR: 3.84; 95% CI: 1.25–11.77), coronaviruses (OR: 3.45; 95% CI: 1.53–7.75) and parainfluenza viruses (OR: 2.18; 95% CI: 1.07–4.47). Rhinitis (OR: 5.07; 95% CI: 1.93–13.36), nasal congestion (OR: 2.03; 95% CI: 1.25–3.31) and cough (OR: 1.91; 95% CI: 1.15–3.17) had positive associations with Moraxella catarrhalis. Furthermore, cough had a positive association with respiratory syncytial virus (OR: 7.20; 95% CI: 1.59–32.71) and parainfluenza viruses (OR: 2.79; 95% CI: 1.02–7.69). Conclusions: The variation of acute symptoms in young children may be influenced by both nasopharyngeal bacteria and respiratory viruses. Our results showed a strong association between fever and respiratory viruses; rhinitis, nasal congestion and cough were associated with M. catarrhalis in the presence of viruses. Further studies are required to determine the possible synergistic role of M. catarrhalis in symptoms of RTI.

Symptoms and Otoscopic Signs in Bilateral and Unilateral Acute Otitis Media

OBJECTIVE: Bilateral acute otitis media (AOM) is considered more severe than unilateral AOM, and several guidelines recommend more active treatment and/or follow-up of bilateral AOM. We studied whether bilateral AOM is a clinically more severe illness than unilateral AOM by comparing symptoms and otoscopic signs between bilateral and unilateral AOM. METHODS: Two hundred thirty-two children aged 6 to 35 months diagnosed with AOM were eligible. We surveyed the symptoms with a structured questionnaire and recorded the otoscopic signs systematically. RESULTS: Ninety-eight children had bilateral and 134 children unilateral AOM. Children with bilateral AOM were more often <24 months than children with unilateral AOM (87% vs 75%; P = .032). Fever (≥38°C) occurred in 54% and 36% (P = .006) and severe conjunctivitis in 16% and 44% (P = .047) of children with bilateral and unilateral AOM, respectively. In 15 other symptoms, we found no overall differences even when adjusted with age. We observed the following severe otoscopic signs in the bilateral and unilateral AOM group, respectively: moderate/marked bulging of tympanic membrane (63% and 40%; P = .001), purulent effusion (89% and 71%; P = .001), bulla formation (11% and 10%; P = .707), and hemorrhagic redness of tympanic membrane (7% and 10%; P = .386). CONCLUSIONS: Bilateral AOM seems to be a clinically only slightly more severe illness than unilateral AOM. Therefore, when assessing AOM severity, bilaterality should not be used as a determining criterion; instead, the child’s symptomatic condition together with otoscopic signs should also be taken into consideration.

Detection of Streptococcus pneumoniae carriage by the Binax NOW test with nasal and nasopharyngeal swabs in young children

The rapid detection of carriage of Streptococcus pneumoniae could assist in the management of pneumococcal infection, such as acute otitis media. We evaluated the reliability of the Binax NOW test in the exclusion and detection of pneumococcal carriage by nasal samples from 139 children and using nasopharyngeal samples from 250 children (aged 6–35 months) with respiratory infection with or without acute otitis media. The Binax NOW test results were compared with culture-based detection of carriage of S. pneumoniae. The Binax NOW test from the nasal samples had a sensitivity of 95%, a specificity of 78%, and the positive and negative predictive values were 83 and 93%, respectively; and for the nasopharyngeal samples the corresponding numbers were 88%, 95%, 96%, and 87%. When rapid knowledge of the carriage status of S. pneumoniae is needed, the Binax NOW test is a reliable method for the exclusion of carriage using nasal sampling, and in the detection of carriage using nasopharyngeal sampling.

Close Follow-up in Children With Acute Otitis Media Initially Managed Without Antimicrobials

Close Follow-up in Children With Acute Otitis Media Initially Managed Without Antimicrobials According to several national guidelines, close follow-up is required if initial observation without antimicrobial agents is chosen for the management of acute otitis media (AOM) in children.1-4 The aim of this study was to examine whether close follow-up with reexamination is needed for children with AOM initially managed without antimicrobial agents who have symptomatic improvement during the first week after diagnosis, as assessed by their parents.

Can nurses exclude middle-ear effusion without otoscopy in young asymptomatic children in primary care?

Abstract Objective. Scandinavian guidelines recommend controlling middle-ear effusion (MEE) after acute otitis media. The study aim was to determine whether nurses without otoscopic experience can reliably exclude MEE with tympanometry or spectral gradient acoustic reflectometry (SG-AR) at asymptomatic visits. Design. Three nurses were taught to perform examinations with tympanometry and SG-AR. Pneumatic otoscopy by the study physician served as the diagnostic standard. Setting. Study clinic at primary health care level. Patients. A total of 156 children aged 6–35 months. Main outcome measures. Predictive values (with 95% confidence interval) for tympanometry and SG-AR, and the clinical usefulness, i.e. the proportion of visits where nurses obtained the exclusive test result from both ears of the child. Results. At 196 visits, the negative predictive value of type A and C1 tympanograms (tympanometric peak pressure > −200 daPa) was 95% (91–97%). Based on type A and C1 tympanograms, the nurse could exclude MEE at 81/196 (41%) of visits. The negative predictive value of SG-AR level 1 result was 86% (79–91%). Based on SG-AR level 1 results, the nurse could exclude MEE at 29/196 (15%) of visits. Conclusion. Tympanograms with tympanometric peak pressure > −200 daPa (types A and C1) obtained by nurses are reliable test results in excluding MEE. However, these test results were obtained at less than half of the asymptomatic visits and, thus, the usefulness of excluding MEE by nurses depends on the clinical setting.