Topical or oral antibiotics in childhood acute otitis media and ear discharge: a randomized controlled non-inferiority trial.

BACKGROUND: Current guidance suggests oral antibiotics can be considered for children with acute otitis media (AOM) and ear discharge, but there is an absence of evidence regarding the relative effectiveness of antibiotic-corticosteroid eardrops. AIM: To establish whether antibiotic-corticosteroid eardrops are non-inferior to oral antibiotics in children with AOM and ear discharge. DESIGN AND SETTING: Open randomized controlled non-inferiority trial set in Dutch primary care. METHODS: Children were randomized to hydrocortisone-bacitracin-colistin eardrops (five drops, three times per day in the discharging ear(s)) or amoxicillin suspension (50 mg per kilogram of body weight per day, divided over three doses administered orally) for 7 days. The primary outcome was the proportion of children with resolution of ear pain and fever at day 3. RESULTS: Between December 2017 and March 2023, 58 of the planned 350 children were recruited due to slow accrual for various reasons. Children assigned to eardrops (n = 26) had lower resolution rates of ear pain and fever at 3 days compared to those receiving oral antibiotics (n = 31): 42% vs 65%; adjusted risk difference 20.3%, 95% confidence interval -5.3% to 41.9%), longer parent-reported ear discharge (6 vs 3 days; P = .04), and slightly higher mean ear pain scores (Likert scale 0-6) over days 1-3 (2.1 vs 1.4, P = .02), but received fewer oral antibiotic courses in 3months (11 for 25 children vs 33 for 30 children), and had less GI upset and rash (12% vs 32% and 8% vs 16%, respectively). CONCLUSION: Early termination stopped us from determining non-inferiority of antibiotic-corticosteroid eardrops. Our limited data, requiring confirmation, suggest that oral antibiotics may be more effective than antibiotic-corticosteroid eardrops in resolving symptoms and shortening the duration of ear discharge.

ISOM 2023 Research Panel 5: Interventions- Vaccines and prevention, medical and surgical treatment, and impact of COVID-19 pandemic.

OBJECTIVES: To identify and synthesize key research advances from the literature published between 2019 and 2023 on the advances in preventative measures, and medical and surgical treatment of uncomplicated otitis media (OM) including the impact of the COVID-19 pandemic on OM management. DATA SOURCES: Medline (PubMed), Embase, and the Cochrane Library. REVIEW METHODS: All relevant original articles published in English between June 2019 and February 2023 were identified. Studies related to guideline adherence, impact of treatment on immune response and/or microbiology, tympanoplasty, Eustachian tube balloon dilatation, mastoidectomy procedures, and those focusing on children with Down's syndrome or cleft palate were excluded. MAIN FINDINGS: Of the 9280 unique records screened, 64 were eligible for inclusion; 23 studies related to medical treatment, 20 to vaccines, 13 to surgical treatment, 6 to prevention (excl. vaccines) and 2 to the impact of COVID-19 on OM management. The level of evidence was judged 2 in 11 studies (17.2 %) and 3 or 4 in the remaining 53 studies (82.8 %) mainly due to the observational design, study limitations or low sample sizes. Some important advances in OM management have been made in recent years. Video discharge instructions detailing the identification and management of pain and fever for parents of children with acute otitis media (AOM) was more effective than paper instructions in reducing symptomatology; compared to placebo, levofloxacin solution was more effective for treating chronic suppurative otitis media, whereas AOM recurrences during two years of follow-up did not differ between children with recurrent AOM who received tympanostomy tube (TT) insertion or medical management. Further, novel pneumococcal conjugate vaccines (PCV) schedules for preventing OM in Aboriginal children appeared ineffective, and a protein-based pneumococcal vaccine had no added value over PCV13 for preventing AOM in native American infants. During the COVID-19 pandemic, a decline in OM and TT case volumes and complications was observed. IMPLICATION FOR PRACTICE AND FUTURE RESEARCH: Whether the observed impact of the COVID-19 pandemic on OM management extends to the post-pandemic era is uncertain. Furthermore, the impact of the pandemic on the conduct of urgently needed prospective methodologically rigorous interventional studies aimed at improving OM prevention and treatment remains to be elucidated since the current report consisted of studies predominantly conducted in the pre-pandemic era.

Effectiveness of analgesic ear drops as add-on treatment to oral analgesics in children with acute otitis media: study protocol of the OPTIMA pragmatic randomised controlled trial.

INTRODUCTION: Ear pain is the most prominent symptom of childhood acute otitis media (AOM). To control the pain and reduce reliance on antibiotics, evidence of effectiveness for alternative interventions is urgently needed. This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM. METHODS AND ANALYSIS: This is a pragmatic, two-arm, individually randomised, open, superiority trial with cost-effectiveness analysis and nested mixed-methods process evaluation in general practices in the Netherlands. We aim to recruit 300 children aged 1-6 years with a general practitioner (GP) diagnosis of AOM and ear pain. Children will be randomly allocated (ratio 1:1) to either (1) lidocaine hydrochloride 5 mg/g ear drops (Otalgan) one to two drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics); or (2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0-10) over the first 3 days. Secondary outcomes include proportion of children consuming antibiotics, oral analgesic use and overall symptom burden in the first 7 days; number of days with ear pain, number of GP reconsultations and subsequent antibiotic prescribing, adverse events, complications of AOM and cost-effectiveness during 4-week follow-up; generic and disease-specific quality of life at 4 weeks; parents' and GPs' views and experiences with treatment acceptability, usability and satisfaction. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Utrecht, the Netherlands, has approved the protocol (21-447/G-D). All parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. TRIAL REGISTRATION: The Netherlands Trial Register: NL9500; date of registration: 28 May 2021. At the time of publication of the study protocol paper, we were unable to make any amendments to the trial registration record in the Netherlands Trial Register. The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors guidelines. The trial was therefore reregistered in ClinicalTrials.gov (NCT05651633; date of registration: 15 December 2022). This second registration is for modification purposes only and the Netherlands Trial Register record (NL9500) should be regarded as the primary trial registration.

[Acute ear discharge, a reason for consultation]. / Een acuut loopoor.

It is often thought that acute ear discharge as a presenting symptom of acute otitis media (AOM) means that the infection is petering out. However, children with AOM presenting with ear discharge due to a spontaneous perforation of the eardrum (AOMd) have a poorer prognosis (i.e. higher rates of ear pain and/or fever at 3-7 days) than those without ear discharge. In this article we emphasize the importance of physical examination and early treatment of children and adults who present with acute ear discharge.

Topical or oral antibiotics for children with acute otitis media presenting with ear discharge: study protocol of a randomised controlled non-inferiority trial.

BACKGROUND: Around 15%-20% of children with acute otitis media present with ear discharge due to a spontaneous tear or perforation of the eardrum (AOMd). Current guidance recommends clinicians to consider oral antibiotics as first-line treatment in this condition. The opening in the eardrum however should allow topical antibiotics to enter the middle ear directly. Local administration of antibiotics does not expose children to systemic side effects and may put less selective resistance pressure on bacteria. Evidence on the effectiveness of this approach in children with AOMd is lacking. METHODS AND ANALYSIS: A primary care-based, open, individually randomised, controlled, non-inferiority trial. The trial aims to recruit 350 children aged 6 months to 12 years with AOMd and ear pain and/or fever. Participants will be randomised to 7 days of hydrocortisone-bacitracin-colistin eardrops five drops three times daily or amoxicillin oral suspension 50 mg/kg body weight per day, divided over three doses. Parents will keep a daily diary of AOM symptoms, adverse events and complications for 2 weeks. In addition, they will record AOM recurrences, healthcare utilisation and societal costs for 3 months. The primary outcome is the proportion of children without ear pain and fever at day 3. Secondary outcomes include ear pain and fever intensity/severity; days with ear discharge; eardrum perforation at 2 weeks; adverse events during first 2 weeks; costs; and cost effectiveness at 2 weeks and 3 months. The primary analyses will be intention-to-treat and per-protocol analyses will be conducted as well. ETHICS AND DISSEMINATION: The medical research ethics committee Utrecht, The Netherlands has given ethical approval (17-400/G-M). Parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. TRIAL REGISTRATION NUMBER: The Netherlands National Trial Register; NTR6723. Date of registration: 27 November 2017.

Common Infections and Antibiotic Prescribing during the First Year of the COVID-19 Pandemic: A Primary Care-Based Observational Cohort Study.

Presentation and antibiotic prescribing for common infectious disease episodes decreased substantially during the first COVID-19 pandemic wave in Dutch general practice. We set out to determine the course of these variables during the first pandemic year. We conducted a retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network. All patients registered in the pre-pandemic year (n = 425,129) and/or during the first pandemic year (n = 432,122) were included. Relative risks for the number of infectious disease episodes (respiratory tract/ear, urinary tract, gastrointestinal, and skin), in total and those treated with antibiotics, and proportions of episodes treated with antibiotics (prescription rates) were calculated. Compared to the pre-pandemic year, primary care presentation for common infections remained lower during the full first pandemic year (RR, 0.77; CI, 0.76-0.78), mainly attributed to a sustained decline in respiratory tract/ear and gastrointestinal infection episodes. Presentation for urinary tract and skin infection episodes declined during the first wave, but returned to pre-pandemic levels during the second and start of the third wave. Antibiotic prescription rates were lower during the full first pandemic year (24%) as compared to the pre-pandemic year (28%), mainly attributed to a 10% lower prescription rate for respiratory tract/ear infections; the latter was not accompanied by an increase in complications. The decline in primary care presentation for common infections during the full first COVID-19 pandemic year, together with lower prescription rates for respiratory tract/ear infections, resulted in a substantial reduction in antibiotic prescribing in Dutch primary care.

A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands.

Introduction: Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands. Material and Methods: Retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods. Results: OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively). Discussion: GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic.

Prevalence and Antimicrobial Resistance of Bacteria in Children With Acute Otitis Media and Ear Discharge: A Systematic Review.

BACKGROUND: Of children with acute otitis media (AOM), 15%-20% present with acute onset ear discharge due to a spontaneous perforation of the tympanic membrane (AOMd). This review aims to quantify the prevalence and antimicrobial resistance (AMR) status of bacteria in children with AOMd in the pneumococcal conjugate vaccine (PCV) era. METHODS: Systematic searches were performed in PubMed, EMBASE and Cochrane Library from inception to June 7, 2019. Two reviewers extracted relevant data and assessed risk of bias independently. All English studies reporting any prevalence and/or AMR data of bacterial middle ear isolates from children with AOMd were included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: Of 4088 unique records retrieved, 19 studies (10,560 children) were included. Overall quality was judged good. Streptococcus pneumoniae (median 26.1%, range 9.1%-47.9%), Haemophilus influenzae (median 18.8%, range 3.9%-55.3%), Staphylococcus aureus (median 12.3%, range 2.3%-34.9%) and Streptococcus pyogenes (median 11.8%, range 1.0%-30.9%) were the most prevalent bacteria. In 76.0% (median, range 48.7%-100.0%, 19 studies, 1,429 children) any bacterium was identified. AMR data were sparse and mainly limited to S. pneumoniae. We found no evidence of a clear shift in the prevalence of bacteria and AMR over time. CONCLUSIONS: In children with AOMd, S. pneumoniae and H. influenzae are the 2 predominant bacteria, followed by S. aureus and S. pyogenes in the post-PCV era. AMR data are sparse and no clearly change over time was observed. Ongoing surveillance of the microbiology profile in children with AOMd is warranted to guide antibiotic selection and to assess the impact of children's PCV status.

Incidence and management of acute otitis media in adults: a primary care-based cohort study.

BACKGROUND: Although primarily considered a childhood disease, acute otitis media (AOM) also occurs in adults. Data on the burden of this condition in adults are, however, scarce. OBJECTIVE: To explore the primary care incidence and current management of AOM in adults. METHODS: All patients aged 15 and older included in the routine health care database of the Julius General Practitioners' Network were followed from 2015 to 2018 (contributing to a total of 1 261 575 person-years). We extracted data on AOM episodes, AOM-related consultations, comorbidities, and antibiotic and analgesic prescriptions. RESULTS: Five thousand three hundred and fifty-eight patients experienced one or more AOM episodes (total number of AOM episodes: 6667; mean 1.2 per patient). The overall AOM incidence was 5.3/1000 person-years and was fairly stable over the study period. Incidence was particularly high in atopic patients (7.3/1000 person-years) and declined with age (from 7.1 in patients 15-39 years of age to 2.7/1000 person-years in those aged 64 years and older). Oral antibiotics, predominantly amoxicillin, were prescribed in 46%, and topical antibiotics in 21% of all episodes. CONCLUSION: Over the past years, the incidence of AOM in adults in primary care has been stable. Oral antibiotic prescription rates resemble those in children with AOM, whereas a remarkably high topical antibiotic prescription rate was observed. Future prognostic research should inform on the need and feasibility of prospective studies into the best management strategy in this condition.

Clinicians' interpretations of point of care urine culture versus laboratory culture results: analysis from the four-country POETIC trial of diagnosis of uncomplicated urinary tract infection in primary care.

Background: Urine culture at the point of care minimises delay between obtaining the sample and agar inoculation in a microbiology laboratory, and quantification and sensitivity results can be available more rapidly in primary care. Objective: To identify the degree to which clinicians' interpretations of a point-of-care-test (POCT) urine culture (Flexicult™ SSI-Urinary Kit) agrees with laboratory culture in women presenting to primary care with symptoms of uncomplicated urinary tract infections (UTI). Methods: Primary care clinicians used the Flexicult™-POCT, recorded their findings and took a photograph of the result, which was interpreted by microbiology laboratory technicians. Urine samples were additionally processed in routine care laboratories. Cross tabulations were used to identify important differences in organism identification, quantification and antibiotic susceptibility between these three sources of data. The influence of various laboratory definitions for UTI on culture were assessed. Results: Primary care clinicians identified 202/289 urine samples (69.9%) as positive for UTI using the Flexicult™-POCT, whereas laboratory culture identified 94-190 (32.5-65.7%) as positive, depending on definition thresholds. 82.9% of samples identified positive for E. coli on laboratory culture were also considered positive for E. coli using the Flexicult™ -POCT, and susceptibilities were reasonably concordant. There were major discrepancies between laboratory staff interpretation of Flexicult™ photographs, clinicians' interpretation of the Flexicult™ test, and laboratory culture results. Conclusion: Flexicult™-POCT overestimated the positivity rate of urine samples for UTI when laboratory culture was used as the reference standard. However, it is unclear whether point-of-care or laboratory based urine culture provides the most valid diagnostic information.

First-year Daycare and Incidence of Acute Gastroenteritis.

BACKGROUND: Daycare attendance has been associated with increased acute gastroenteritis (AGE) incidence in the first years of life. We investigated the effects of first-year daycare attendance on AGE incidence and primary care contact rate up to age 6 years. METHODS: Children enrolled in the Wheezing Illnesses Study Leidsche Rijn cohort were managed until age 6 years. Data on primary care diagnosed AGE episodes and number of associated contacts per episode were collected from health records. Children were categorized according to first year daycare attendance and age-month at entry when applicable. Generalized estimating equations were used to assess associations between first-year daycare and AGE incidence or primary care contact rate. RESULTS: A total of 1344 out of 2220 children (83%) attended daycare before age 1 year. Overall, the 6-year primary care AGE incidence rate (IR) among first-year daycare attendees and nonattendees was comparable (IR: 12.2/100 vs 13.3/100 child-years). First-year daycare attendees had a higher AGE incidence during the first year (IRR: 1.13; 95% confidence interval: 1.06-1.21) and lower during the third to sixth year of age compared with nonattendees (P < .001). The daycare-associated increase in AGE incidence was most pronounced during the first 12 months after enrollment into daycare and demonstrated clear seasonality. A similar pattern was observed for primary care contact rate per AGE episode. CONCLUSIONS: First-year daycare attendance advances the timing of AGE infections, resulting in increased AGE disease burden in the first year and relative protection thereafter. Protection against AGE infection persists at least up to age 6 years. Future studies should address whether this protective effect persists during later childhood.