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Health care workers are at risk of acquiring SARS-CoV-2 infection. Our aim was to study the prevalence of SARS-CoV-2 nucleoprotein and spike protein specific antibodies in health care workers with occupational exposure to COVID-19 in Turku, Finland, from May to December 2020.Health care workers of Turku University Hospital units caring for COVID-19 patients or handling clinical SARS-CoV-2 samples were invited to participate in the study. The presence of SARS-CoV-2 nucleoprotein and spike protein specific IgG antibodies were analysed with in-house enzyme immunoassay.At study enrolment, only one of the 222 (0.5%) study participants was seropositive for SARS-CoV-2 protein specific antibodies. Two additional study participants (2/222, 0.9%) seroconverted during the follow-up. All these participants were diagnosed with a RT-PCR-positive COVID-19 infection before turning seropositive.In our study population, the prevalence of SARS-CoV-2 seropositivity remained low. The absence of seropositive cases without previous RT-PCR confirmed infections demonstrate good access to diagnostics. In addition to high vaccine coverage, high standards of infection prevention practices and use of standard personal protective equipment seem sufficient in preventing occupational SARS-CoV-2 infection in a setting with low number of circulating virus. However, it remains unclear whether similar protective practices would also be effective against more transmissible SARS-CoV-2 variants.

Background Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primes the immune system; thus individuals who have recovered from infection have enhanced immune responses to subsequent vaccination (hybrid immunity). However, it remains unclear how well hybrid immunity induced by severe or mild infection can cross-neutralize emerging variants. We aimed to compare the strength and breadth of antibody responses in vaccinated recovered and uninfected subjects. Methods We measured spike-specific immunoglobulin (Ig)G and neutralizing antibodies (NAbs) from vaccinated subjects including 320 with hybrid immunity and 20 without previous infection. From 29 subjects with a previous severe or mild infection, we also measured NAb responses against Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529/BA.1) variants following vaccination. Results A single vaccine dose induced 2-fold higher anti-spike IgG concentrations and up to 4-fold higher neutralizing potency of antibodies in subjects with a previous infection compared with vaccinated subjects without a previous infection. Hybrid immunity was more enhanced after a severe than a mild infection, with sequentially decreasing NAb titers against Alpha, Beta, Delta, and Omicron variants. We found similar IgG concentrations in subjects with a previous infection after 1 or 2 vaccine doses. Conclusions Hybrid immunity induced strong IgG responses, particularly after severe infection. However, the NAb titers were low against heterologous variants, especially against Omicron.

Vaccination shows efficacy in protecting from COVID-19, but regime and dosing optimization is still ongoing. Here the authors show that BNT162b2, mRNA-1273, or their combination with ChAdOx1 induces similar antibody responses, and those receiving three doses of BNT162b2 induce neutralizing antibodies against the Omicron variant. Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.

Background Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity. Methods This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3-23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008. Results Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing. Conclusions Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides strong evidence that the second dose of the BNT162b2 vaccine induces efficient cross-neutralization of SARS-CoV-2 variants currently circulating in the world.

Background Despite concerns that antimicrobial treatment of prevalent infections may select for drug-resistant bacteria, the effects of antimicrobial treatment on colonization dynamics have not been well quantified. Methods We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-nonsusceptible (PNSP) lineages at the end of treatment and 15, 30, and 60 days after treatment in a previously conducted randomized, double-blinded, placebo-controlled trial of amoxicillin-clavulanate for stringently defined acute otitis media. Results In intention-to-treat analyses, immediate treatment with amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95% confidence interval [CI], 76%-96%) at the end of treatment and by 27% (-3%-49%) after 60 days but did not alter PNSP carriage prevalence. By the end of treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared with 61% of PSSP carriers who received placebo; impacts of amoxicillin-clavulanate persisted at least 60 days after treatment among children who carried PSSP at enrollment. Amoxicillin-clavulanate therapy reduced PSSP acquisition by >80% over 15 days. Among children who carried PNSP at enrollment, no impacts on carriage prevalence of S. pneumoniae, PSSP, or PNSP were evident at follow-up visits. Conclusions Although the absolute risk of carrying PNSP was unaffected by treatment, antimicrobial therapy conferred a selective impact on colonizing pneumococci by accelerating clearance and delaying acquisition of PSSP.

Background Acute otitis media (AOM) induces middle-ear effusion (MEE), which affects hearing. The effect of antimicrobial treatment on the resolution of MEE is controversial, and the factors that affect resolution are unknown. Methods We studied the effect of antimicrobial treatment on the time to the resolution of MEE as a secondary objective in our randomized double-blind placebo-controlled trial. Children aged 6 to 35 months with stringently diagnosed AOM were allocated to receive amoxicillin-clavulanate (161 patients) or placebo (158 patients) for 7 days and closely followed for 3 months. This study was registered at ClinicalTrials.gov (identifier NCT00299455). Results The median times to resolution of MEE were 20 days (95% confidence interval [CI], 16-24 days) and 29 days (95% CI, 26-32 days) in the amoxicillin-clavulanate and placebo groups, respectively (P = .10). The resolution of MEE was confirmed in 138 (86%) of 161 and 132 (84%) of 158 patients in the amoxicillin-clavulanate and placebo groups, respectively (P = .59). In multivariable analysis, the resolution of MEE was prolonged most significantly by at least 1 recurrence of AOM during follow-up. MEE resolved in 65 (65%) of 100 patients with a recurrence of AOM during follow-up and in 205 (94%) of 219 of those without a recurrence (P < .001) (median times to resolution, 67 vs 15 days, respectively; P < .001). Conclusions Immediate antimicrobial treatment of AOM does not significantly affect the resolution of MEE in young children. Subsequent recurrences of AOM are a major reason for the persistence of MEE.

Objective To summarize recently published key articles on the topics of biomedical engineering, biotechnology and new models in relation to otitis media (OM). Data sources Electronic databases: PubMed, Ovid Medline, Cochrane Library and Clinical Evidence (BMJ Publishing). Review methods Articles on biomedical engineering, biotechnology, material science, mechanical and animal models in OM published between May 2015 and May 2019 were identified and subjected to review. A total of 132 articles were ultimately included. Results New imaging technologies for the tympanic membrane (TM) and the middle ear cavity are being developed to assess TM thickness, identify biofilms and differentiate types of middle ear effusions. Artificial intelligence (AI) has been applied to train software programs to diagnose OM with a high degree of certainty. Genetically modified mice models for OM have further investigated what predisposes some individuals to OM and consequent hearing loss. New vaccine candidates protecting against major otopathogens are being explored and developed, especially combined vaccines, targeting more than one pathogen. Transcutaneous vaccination against non-typeable Haemophilus influenzae has been successfully tried in a chinchilla model. In terms of treatment, novel technologies for trans-tympanic drug delivery are entering the clinical domain. Various growth factors and grafting materials aimed at improving healing of TM perforations show promising results in animal models. Conclusion New technologies and AI applications to improve the diagnosis of OM have shown promise in pre-clinical models and are gradually entering the clinical domain. So are novel vaccines and drug delivery approaches that may allow local treatment of OM. IMPLICATIONS FOR PRACTICE: New diagnostic methods, potential vaccine candidates and the novel trans-tympanic drug delivery show promising results, but are not yet adapted to clinical use.

Introduction: Implementation of pediatric telemedicine has been emphasized. We examined whether parents could perform smartphone otoscopy for the diagnosis of otitis media. Materials and M...

BackgroundConcerns that antimicrobial treatment may foster selection and transmission of resistant bacterial lineages have led to conflicting guidelines for clinical management of common non-severe infections. However, the impact of antimicrobial treatment on colonization dynamics is poorly understood. We used data from a previously-conducted trial of amoxicillin-clavulanate therapy for acute otitis media (AOM) to understand how antimicrobial treatment impacts the acquisition and clearance of Streptococcus pneumoniae lineages with varying susceptibility to penicillin.Methods and findingsWe measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible S. pneumoniae (PSSP) and penicillin–non-susceptible S. pneumoniae (PNSP) lineages at end-of-treatment and 15d, 30d, and 60d after treatment in a previously-conducted randomized, double-blind, placebo-controlled trial. Analyses were not specified in the original protocol. Among children 6-35 months of age with stringently-defined AOM, 162 were assigned amoxicillin-clavulanate, and 160 were assigned placebo. Children who did not show clinical improvement received open-label antimicrobial rescue treatment with amoxicillin-clavulanate irrespective of the randomized treatment assignment, to which both patients and physicians were blinded. The intention-to-treat populations of the intervention and placebo arms thus received care resembling immediate antimicrobial therapy and watchful waiting, respectively. Immediate amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95%CI: 76-96%) at end-of-treatment and by 27% (–3-49%) after 60d, but did not measurably alter PNSP carriage prevalence throughout follow-up. By end-of-treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared to 61% of PSSP carriers who received placebo; differences in carriage prevalence persisted at least 60d after treatment among children who carried PSSP at enrollment. Among children not carrying pneumococci at enrollment, amoxicillin-clavulanate reduced PSSP acquisition by >80% over 15d. Among children who carried PNSP at enrollment, no differences in carriage prevalence of S. pneumoniae, PSSP, or PNSP were detected at follow-up visits.ConclusionsIn a setting with low PNSP prevalence, antimicrobial therapy for AOM conferred a selective impact on colonizing S. pneumoniae by accelerating clearance, and delaying acquisition, of penicillin-susceptible lineages. Absolute risk of carrying PNSP was unaffected by treatment (ClinicalTrials.gov: NCT00299455; Funding: NIH/NIGMS).

Objective Since acute otitis media (AOM) is the most prevalent bacterial infection in young children, the reliable exclusion of AOM by nurses might save physicians’ time for other duties. The study aim was to determine whether nurses without otoscopic experience can reliably use tympanometry or spectral gradient acoustic reflectometry (SG-AR) to exclude AOM. Design Three nurses were trained, who performed 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. 281 children 6–35 months of age. 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 459 visits, the negative predictive value of type A and C1 tympanograms (tympanometric peak pressure >–200 daPa) was 94% (91–97%). Based on type A and C1 tympanograms, the nurse could exclude AOM at 94/459 (20%) of visits. The negative predictive value of SG-AR level 1 result (>95°) was 94% (89–97%). Based on the SG-AR level 1 result, the nurse could exclude AOM at 36/459 (8%) of visits. Conclusion Type A and C1 tympanograms and SG-AR level 1 results obtained by nurses are reliable test results in excluding AOM. However, the clinical usefulness of these test results is limited by their rarity. Type A and C1 tympanograms were obtained by nurses from both ears of the child only at one-fifth of the symptomatic visits.Key PointsAcute otitis media (AOM) is the most prevalent bacterial infection in young children. Nurses’ role in excluding AOM is unknown.Type A and C1 tympanograms (tympanometric peak pressure >–200 daPa) obtained by nurses are reliable test results in excluding AOM.With type A and C1 tympanograms, nurses could exclude AOM only at one-fifth of the symptomatic visits.The clinical usefulness of the exclusion of AOM performed by nurses seems to be limited.

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.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.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).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.

Objective Spectral gradient acoustic reflectometry (SG-AR) can be used to detect middle ear effusion (MEE). Since both families and primary health care systems carry the burden of otitis media, our aim was to determine whether layman parents could be taught to use the SG-AR reliably. Methods We enrolled 359 children (age 6–35 months) whose parents were willing to use SG-AR at home. The parents were asked to perform bilateral SG-AR daily on their child. In this study, we included children who had undergone successful parental home SG-AR examination performed on the same day that a physician had also performed successful SG-AR examination and pneumatic otoscopy at the study clinic. We compared the parental and study physician SG-AR examination results to the study physicians′ pneumatic otoscopy, which served as the diagnostic standard. Results We analyzed 571 successful parental home SG-AR examinations performed on the same day that a study physician had performed a successful SG-AR examination and pneumatic otoscopy at the study clinic. None of the evaluated SG-AR level combinations resulted in both high sensitivity and specificity. For symptomatic visits, the negative predictive value of a parental SG-AR level 1 to detect MEE was 64%. For parental SG-AR levels 4–5, the positive predictive value to detect MEE was 88%. However, for asymptomatic visits, the negative predictive value of a parental SG-AR level 1 to detect MEE was 83%. Conclusion This study showed that layman parents are able to use the SG-AR technically successfully. In symptomatic children, parentally obtained SG-AR level 1 examination is not adequate to exclude MEE. However, parentally obtained SG-AR levels 4–5 do indicate the presence of MEE. At the same time, in asymptomatic children, parentally obtained SG-AR level 1 examination seems to indicate a healthy middle ear. From the perspective of primary care, the implementation of parental SG-AR examinations in the diagnostic chain of otitis media would be intriguing. This study showed that the possibilities lie in the follow up of the resolution of MEE after an episode of OM in asymptomatic children. However, it seems that currently, the SG-AR technique is an obstacle for wider clinical implementation.

BackgroundAll-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of non-vaccine pneumococcal serotypes escaping immune pressure. To understand the basis for declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeableHaemophilus influenzae(NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout.MethodsData included OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1588) from unvaccinated asymptomatic children in the same population. We compared pneumococcal serotype diversity across carriage and disease isolates with and without NTHi co-isolation. We also measured associations between pneumococcal phenotype and rate of progression from colonization to OM in the presence and absence of NTHi.ResultsWhereas pneumococcal serotype diversity in single-species OM is lower than in single-species colonization, serotype diversity does not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and these differences were attenuated in polymicrobial episodes. Vaccine-serotype pneumococci had higher rates of progression than non-vaccine serotypes. While serotype invasiveness was a weak predictor of OM progression rate, efficient capsular metabolic properties—traditionally thought to serve as an advantage in colonization—predicted an enhanced rate of progression to complex OM.ConclusionsThe lower capacity of non-vaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs.

BACKGROUND AND OBJECTIVES:Antimicrobial treatment is effective in the management of acute otitis media (AOM), but approximately half of the children may recover without antimicrobial agents. By identifying patients who may not require antimicrobial treatment for the management of AOM, the use of antimicrobial agents could be substantially reduced. Our aim was to identify subgroups of children with AOM who would benefit most from antimicrobial treatment and children who could be suitable for initial observation.METHODS:This is a secondary analysis of randomized, double-blind, placebo-controlled trial. Children 6 to 35 months of age with AOM (N = 319) were randomly allocated to receive amoxicillin-clavulanate (40/5.7 mg/kg per day) or placebo for 7 days. Our primary outcome was time until treatment failure.RESULTS:Treatment failure occurred in 31.7% of all children. Older age (24–35 months) and peaked tympanogram at entry decreased the hazard for treatment failure (hazard ratio, 0.53; 95% confidence interval [CI], 0.29 to 0.96; P = .04; and hazard ratio, 0.43; 95% CI, 0.21 to 0.88; P = .02, respectively). The rate difference for treatment failure between antimicrobial treatment and placebo groups was highest among children with severe bulging of the tympanic membrane (11.1% vs 64.1%; rate difference −53.0%; 95% CI, −73.5% to −32.4%), resulting in a number needed to treat of 1.9.CONCLUSIONS:Children with severe bulging of the tympanic membrane seem to benefit most from antimicrobial treatment of AOM. On the other hand, children with peaked tympanogram (A and C curves) may be optimal candidates for initial observation.

Objective Tympanometry can be used to detect middle ear effusion (MEE). As the need for rearrangement of clinical resources at the primary care level increases, it is important to determine whether layman parents could be taught to use the tympanometer reliably, aiming to reduce unnecessary physician visits during respiratory tract infections. Methods From our AOM treatment trial we enrolled 78 children (age 6–35 months) who had persistent MEE, parents were voluntary and willing to use a tympanometer at home, the child was sufficiently co-operative, and parents learned technically the use of the tympanometer. At home, parents were asked to perform daily bilateral tympanometry on their child. We included those parental tympanometric examinations, to which the corresponding tympanometric examination, within one day by a study physician was available. Parental tympanometric examinations were compared to the pneumatic otoscopy by a study physician which served as the diagnostic standard. Results This study involved 78 children and a total of 432 parental tympanometric examinations. From these 432 examinations, parents obtained an interpretable tympanogram in 83% (359/432) and physicians in 91% (393/432) (absolute rate difference 8%, 95% CI 3–12%). Both obtained an interpretable tympanogram from the same ear in 75% (326/432) of the tympanometric examinations. Of these 326 interpretable examinations, parents and physicians were in accordance with either a peaked or a flat tympanogram in 88% of examinations (288/326) (kappa-value 0.77). When the tympanogram was peaked, pneumatic otoscopy indicated healthy middle ear in 72% (122/169) of parental and in 69% (149/217) of study physicians’ tympanometric examinations (absolute rate difference 4%, 95% CI −6% to 13%). When the tympanogram was flat, pneumatic otoscopy indicated any MEE in 92% of parental (174/190) and in 96% (169/176) of study physicians’ tympanometric examinations (absolute rate difference 4%, 95% CI −9% to 1%). Conclusion This study showed that layman parents are able to use tympanometry technically successfully, and that the parental tympanometric examinations are as reliable as those obtained by study physicians.

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 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.

Summary Objectives To understand relationships between microbes in pathogenesis of acute otitis media during respiratory tract infections, we compared nasopharyngeal bacteria and respiratory viruses in symptomatic children with and without AOM. Methods We enrolled children (6–35 months) with acute symptoms suggestive of AOM and analyzed their nasopharyngeal samples for bacteria by culture and for 15 respiratory viruses by PCR. Non-AOM group had no abnormal otoscopic signs or only middle ear effusion, while AOM group showed middle ear effusion and acute inflammatory signs in pneumatic otoscopy along with acute symptoms. Results Of 505 children, the non-AOM group included 187 and the AOM group 318. One or more bacterial AOM pathogen ( Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis ) was detected in 78% and 96% of the non-AOM and AOM group, respectively ( P S. pneumoniae and H. influenzae , each alone, increased risk of AOM (odds ratio (OR) 2.92; 95% confidence interval (CI), .91–9.38, and 5.13; 1.36–19.50, respectively) and co-colonization with M. catarrhalis further increased risk (OR 4.36; 1.46–12.97, and 9.00; 2.05–39.49, respectively). Respiratory viruses were detected in 90% and 87% of the non-AOM and AOM group, respectively. RSV was significantly associated with risk of AOM without colonization by bacterial AOM pathogens (OR 6.50; 1.21–34.85). Conclusions Co-colonization by M. catarrhalis seems to increase risk of AOM and RSV may contribute to AOM pathogenesis even without nasopharyngeal bacterial colonization.

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.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.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.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.

Objective Spectral gradient acoustic reflectometry (SG-AR) may be used to detect middle ear effusion. Our aim was to investigate whether increasing SG-AR levels between two SG-AR examinations indicate deterioration from a healthy middle ear to acute otitis media (AOM). Methods We enrolled 185 children (age 6–35 months) whose parents were willing to use the SG-AR at home daily. Measurement pairs of parental home SG-AR examination results were generated and analyzed. There was one SG-AR examination result obtained within ±1 day of the reference visit and another result within ±1 day of the subsequent visit. We defined the SG-AR level as increasing when the difference between two measurements was ≥2 levels from a lower to a higher level, suggesting development of AOM. When the SG-AR level difference was ≤1, we defined this no change of the SG-AR level. The middle ear diagnosis was determined by pneumatic otoscopy at the study clinic. Results 361 paired SG-AR home measurements were obtained. The reference measurement was related to a healthy middle ear as determined by pneumatic otoscopy. Increasing SG-AR levels (59/361), were 63% (95% CI 50%–74%) sensitive and 94% (91%–97%) specific for deterioration of a healthy middle ear to AOM. The positive predictive value was 71% (58%–82%) and the negative predictive value was 92% (88%–95%). When there was no SG-AR level difference between the SG-AR examinations, the corresponding figures were 88% (95% CI 84%–92%), 69% (56%–79%), 93% (89%–95%) and 57% (45%–68%), respectively. Conclusions This study shows that increasing SG-AR levels might not be sufficiently sensitive to detect deterioration of the middle ear status from healthy middle ear to AOM in symptomatic children. Importantly, however, the development of AOM seems to be unlikely in an initially healthy middle ear when there is no difference between the SG-AR levels in two separate measurements.

The efficacy of antimicrobial treatment in children with acute otitis media remains controversial.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.Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P0.001). 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; P0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P0.001). 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 (P0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04).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.).

BACKGROUND: Both treatment guidelines and the amount of antibiotics used for acute otitis media (AOM) vary across western countries. Parental expectations and their awareness of antimicrobial use and resistance, which may also be influenced by the guidelines, are not yet completely known. OBJECTIVE: To compare parental experiences and opinions regarding the management of AOM in children with AOM in Finland and The Netherlands. METHODS: We sent the questionnaires via public day care in Turku, Finland, and Utrecht, The Netherlands. We asked about family background, child's history of AOM and parental experiences and attitudes about AOM treatment and antimicrobial resistance. RESULTS: Of 1151 participants, 83% in Finland and 49% in The Netherlands had had at least one episode of AOM. Antibiotics were used more frequently in Finland than in The Netherlands, 99% versus 78%, respectively. More Finnish parents reported to believe that antibiotics are necessary in the treatment of AOM as compared to Dutch parents. Use of analgesics for AOM was similar (80% in Finland and 86% in The Netherlands). One-third of the parents had discussed resistance with their doctor. According to parental experiences, antimicrobial resistance had caused more problems in Finland than in The Netherlands (20% versus 2%). Finally, 88% of parents in Finland and 65% in The Netherlands were worried that bacteria could become resistant to antibiotics. CONCLUSIONS: Treatment practices and parental expectations seem to interact with each other. Therefore, if we aim to change AOM treatment practices, we have to modify both guidelines and parental expectations.

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.

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.

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.

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.