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1.
PLoS One ; 19(6): e0304742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38885271

RESUMO

BACKGROUND: Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies. METHODS: RCTs and observational studies that compared antibiotics to placebo or watchful waiting for pediatric clinician diagnosed AOM were identified [PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, and Web of Science] and reviewed for meta-analysis. Two reviewers independently extracted study characteristics, patient characteristics, and outcomes. We assessed publication bias, study bias with ROBINS-1 and RoB-2 and used random-effects models to assess treatment effects. RESULTS: 24 studies were included. Antibiotics decreased the risk of acute mastoiditis [incidence 0.02%, RR 0.48, 95% CI 0.40-0.59; NNT 5,368]. This protective effect may be underestimated because of misclassification of non-suppurative conditions as AOM. Intracranial complications remained too rare to assess. Antibiotics markedly increased the risk of adverse effects [incidence 10.5%, RR 1.49, 1.27-1.73; NNH 23]. Studies used non-specific criteria for acute mastoiditis, potentially underestimating treatment effects. CONCLUSIONS: Prompt antibiotic therapy reduces the risk for some AOM complications. The NNT to prevent serious, rare complications is high, while the NNH is relatively low. Large-scale population-based observational studies using real-world datasets with validated measures of severe complications are needed to improve understanding of risk factors for serious AOM complications, facilitate more selective antibiotic therapy, and optimize individual outcomes and public health.


Assuntos
Antibacterianos , Otite Média , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Otite Média/tratamento farmacológico , Criança , Doença Aguda , Pré-Escolar , Mastoidite/tratamento farmacológico , Mastoidite/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Medicine (Baltimore) ; 103(25): e38616, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905364

RESUMO

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection. PATIENT CONCERNS: We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated. DIAGNOSIS: The patient fulfilled diagnostic criteria for HLH. INTERVENTIONS: Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed. OUTCOMES: After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized. LESSIONS: The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica , Otite Média , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Masculino , Pré-Escolar , Otite Média/complicações , Otite Média/tratamento farmacológico , Doença Aguda , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem , Etoposídeo/uso terapêutico , Etoposídeo/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico
3.
Int J Biol Macromol ; 269(Pt 1): 131794, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38697434

RESUMO

A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.


Assuntos
Amoxicilina , Antibacterianos , Celulose , Ciprofloxacina , Nanofibras , Celulose/química , Celulose/análogos & derivados , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Nanofibras/química , Animais , Ratos , Amoxicilina/farmacologia , Amoxicilina/química , Antibacterianos/farmacologia , Antibacterianos/química , Hidroxibutiratos/química , Hidroxibutiratos/farmacologia , Humanos , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Poliésteres/química , Liberação Controlada de Fármacos , Alicerces Teciduais/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Proibitinas , Portadores de Fármacos/química , Masculino
4.
J Antimicrob Chemother ; 79(6): 1397-1406, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38714502

RESUMO

BACKGROUND: It is crucial to understand the trends in paediatric antibiotic prescribing and serious and nonserious infections to improve antibiotic prescribing practices for children in ambulatory care. OBJECTIVES: Assessing trends in paediatric antibiotic prescribing and infection incidence in general practice from 2002 to 2022. METHODS: In this retrospective cohort study using INTEGO network data from 162 507 patients in Flanders (Belgium), we calculated antibiotic prescribing rates and proportions alongside incidence rates of serious and nonserious infections, stratified by age (0-1, 2-6, 7-12 years) and municipality. We performed autoregressive moving average time-series analyses and seasonality analyses. RESULTS: From 2002 to 2022, antibiotic prescribing rate decreased significantly: 584/1000 person-years (PY) (95% CI 571-597) to 484/1000PY (95% CI 478-491); so did antibiotic overall prescribing proportion: 46.3% (95% CI 45.1-47.6) to 23.3% (95% CI 22.9-23.7) (59.3% amoxicillin and 17.8% broad spectrum). Prescribing proportions dropped significantly for nonserious (45.6% to 20.9%) and increased for serious infections (64.1% to 69.8%). Proportions significantly dropped for acute suppurative otitis media (74.7% to 64.1%), upper respiratory tract infections (44.9% to 16.6%), bronchitis/bronchiolitis (73.6% to 44.1%) and acute tonsillopharyngitis (59.5% to 21.7%), while significantly increasing for pneumonia (65.2% to 80.2%). Nonserious and serious infection incidence rates increased from 785/1000PY and 34.2/1000PY to 1223/1000PY and 64.1/1000PY, respectively. Blood and CRP testing proportions increased significantly. CONCLUSIONS: Antibiotic prescribing in general practice for children declined from 2002 to 2022. Further targeted antibiotic stewardship initiatives are needed to reduce the use of broad-spectrum antibiotics and antibiotic prescribing for conditions such as otitis media and bronchitis/bronchiolitis.


Assuntos
Antibacterianos , Medicina Geral , Humanos , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Lactente , Medicina Geral/estatística & dados numéricos , Medicina Geral/tendências , Feminino , Masculino , Estudos Retrospectivos , Estudos Longitudinais , Recém-Nascido , Incidência , Bélgica/epidemiologia , Padrões de Prática Médica/tendências , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Otite Média/tratamento farmacológico , Otite Média/epidemiologia
5.
J Antimicrob Chemother ; 79(6): 1289-1293, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38629145

RESUMO

BACKGROUND: Antibiotic exposure increases antimicrobial resistance and has also been associated with long-term harms, including allergies, inflammatory diseases and weight gain. We assessed antibiotic exposure in the first 2 years of life in Australian children, the factors influencing this and its appropriateness. METHODS: Data from 1201 participants in the MIS BAIR randomized controlled trial were used. Multivariable logistic regression was used to identify factors associated with antibiotic exposure. RESULTS: At 1 and 2 years of age, exposure to at least one course of antibiotics was 43% and 67%, with the highest first antibiotic prescription rate between 9 and 18 months. Amoxicillin was the most frequently used antibiotic (59%), followed by cefalexin (7%). The most common diagnoses for which antibiotics were prescribed were respiratory tract infections from 0 to 6 months of age and otitis media from 6 to 12 months. Factors associated with antibiotic exposure from 0 to 12 months of age were delivery by Caesarean section (adjusted odd-ratio (aOR) 1.5, 95%CI 1.1-1.9), birth in winter (aOR 1.7, 95%CI 1.2-2.4), maternal antibiotic exposure during the last trimester of pregnancy (aOR 1.6, 95%CI 1.1-2.3), cessation of breastfeeding by 6 months of age (aOR 1.5, 95%CI 1.1-2.0) and day-care attendance (aOR 1.4, 95%CI 1.1-1.8). Based on parent-reported questionnaires, 27% of infants were treated in the first year of life for conditions unlikely to need antibiotic treatment. CONCLUSION: At least two-thirds of children were prescribed antibiotics in the first 2 years of life, and more than a quarter of these exposures may have been unnecessary.


Assuntos
Antibacterianos , Prescrição Inadequada , Otite Média , Infecções Respiratórias , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Lactente , Feminino , Masculino , Austrália , Prescrição Inadequada/estatística & dados numéricos , Recém-Nascido , Infecções Respiratórias/tratamento farmacológico , Otite Média/tratamento farmacológico , Pré-Escolar
6.
J Pediatric Infect Dis Soc ; 13(6): 328-333, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38581154

RESUMO

Acute respiratory tract infections (ARTIs) account for most antibiotic prescriptions in pediatrics. Although US guidelines continue to recommend ≥10 days antibiotics for common ARTIs, evidence suggests that 5-day courses can be safe and effective. Academic imprinting seems to play a major role in the continued use of prolonged antibiotic durations. In this report, we discuss the evidence supporting short antibiotic courses for group A streptococcal pharyngitis, acute otitis media, and acute bacterial rhinosinusitis. We discuss the basis for prolonged antibiotic course recommendations and recent literature investigating shorter courses. Prescribers in the United States should overcome academic imprinting and follow international trends to reduce antibiotic durations for common ARTIs, where 5 days is a safe and efficacious course when antibiotics are prescribed.


Assuntos
Antibacterianos , Faringite , Infecções Respiratórias , Sinusite , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Doença Aguda , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Faringite/tratamento farmacológico , Faringite/microbiologia , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Criança , Esquema de Medicação , Infecções Estreptocócicas/tratamento farmacológico , Guias de Prática Clínica como Assunto , Rinite/tratamento farmacológico , Rinite/microbiologia , Estados Unidos , Streptococcus pyogenes/efeitos dos fármacos
7.
Int J Nanomedicine ; 19: 2995-3007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559446

RESUMO

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed. Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs. Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 µg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 µg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs. Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Otite Média , Infecções Estafilocócicas , Óxido de Zinco , Humanos , Staphylococcus aureus , Radical Hidroxila , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Antibacterianos/química , Otite Média/tratamento farmacológico , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química
8.
JAMA Pediatr ; 178(4): 401-407, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38436941

RESUMO

Importance: Acute otitis media (AOM) is a frequently diagnosed illness in children, yet the accuracy of diagnosis has been consistently low. Multiple neural networks have been developed to recognize the presence of AOM with limited clinical application. Objective: To develop and internally validate an artificial intelligence decision-support tool to interpret videos of the tympanic membrane and enhance accuracy in the diagnosis of AOM. Design, Setting, and Participants: This diagnostic study analyzed otoscopic videos of the tympanic membrane captured using a smartphone during outpatient clinic visits at 2 sites in Pennsylvania between 2018 and 2023. Eligible participants included children who presented for sick visits or wellness visits. Exposure: Otoscopic examination. Main Outcomes and Measures: Using the otoscopic videos that were annotated by validated otoscopists, a deep residual-recurrent neural network was trained to predict both features of the tympanic membrane and the diagnosis of AOM vs no AOM. The accuracy of this network was compared with a second network trained using a decision tree approach. A noise quality filter was also trained to prompt users that the video segment acquired may not be adequate for diagnostic purposes. Results: Using 1151 videos from 635 children (majority younger than 3 years of age), the deep residual-recurrent neural network had almost identical diagnostic accuracy as the decision tree network. The finalized deep residual-recurrent neural network algorithm classified tympanic membrane videos into AOM vs no AOM categories with a sensitivity of 93.8% (95% CI, 92.6%-95.0%) and specificity of 93.5% (95% CI, 92.8%-94.3%) and the decision tree model had a sensitivity of 93.7% (95% CI, 92.4%-94.9%) and specificity of 93.3% (92.5%-94.1%). Of the tympanic membrane features outputted, bulging of the TM most closely aligned with the predicted diagnosis; bulging was present in 230 of 230 cases (100%) in which the diagnosis was predicted to be AOM in the test set. Conclusions and Relevance: These findings suggest that given its high accuracy, the algorithm and medical-grade application that facilitates image acquisition and quality filtering could reasonably be used in primary care or acute care settings to aid with automated diagnosis of AOM and decisions regarding treatment.


Assuntos
Inteligência Artificial , Otite Média , Criança , Humanos , Otoscopia/métodos , Otite Média/diagnóstico , Otite Média/tratamento farmacológico , Membrana Timpânica , Algoritmos
9.
J Int Adv Otol ; 20(1): 81-84, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38454294

RESUMO

Established treatment strategies for nontuberculous mycobacterial (NTM) infections are currently lacking, and whether surgical treatment should be applied in combination with antibiotic therapy remains debatable. Here, we report a case of bilateral otitis media caused by Mycobacterium abscessusa, a highly antibiotic-resistant bacterium. Many reported cases of NTM otitis media are unilateral, in which hearing of the contralateral ear is preserved. In the present case, strategies to improve hearing outcomes were considered, as both ears were affected. A 27-year-old woman presented with bilateral otorrhea that had lasted for the past 9 months. Bacterial culture showed M. abscessus in both ears. Based on drug sensitivity tests, clarithromycin, amikacin, and imipenem were administered. Three days after treatment initiation, diseased tissues were removed from the right middle ear, which had impaired hearing. On day 38, otorrhea stopped in both ears, and the hearing improved. Computed tomography revealed air in both middle ears. No apparent recurrence was detected. Under the same antibiotic therapy, resolution of diseased tissues and improvement in hearing were similar between the ears with and without surgery, suggesting that surgery is not always necessary. This finding may be incorporated into the treatment guidelines for NTM infections in the future.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Otite Média , Feminino , Humanos , Adulto , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico
10.
BMJ Case Rep ; 17(3)2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471705

RESUMO

A female infant presented to an Irish hospital with a 4-day history of fever, irritability and reduced oral intake. Initial inflammatory markers were significantly elevated, an erythematous tympanic membrane was noted on examination and an initial diagnosis of acute otitis media was made. By the third hospital day, the infant was noted to be irritable when being lifted up; pseudoparalysis of the right upper limb was observed. A radiograph of the right shoulder was normal; MRI identified acute scapular osteomyelitis with subperiosteal abscess formation. The child underwent 3 washout procedures and received 6 weeks of antibiotic therapy, with full clinical recovery at 3 months. This case highlights the importance of remaining flexible in the context of an evolving presentation and recognising hallmarks of musculoskeletal infection, fever, localised pain and pseudoparalysis. Additionally, we review the literature to highlight clues in diagnosis, treatment and outcome for paediatric acute scapular osteomyelitis.


Assuntos
Osteomielite , Otite Média , Feminino , Humanos , Lactente , Doença Aguda , Antibacterianos/uso terapêutico , Febre/tratamento farmacológico , Osteomielite/diagnóstico , Otite Média/tratamento farmacológico , Dor/tratamento farmacológico , Radiografia
12.
NPJ Biofilms Microbiomes ; 10(1): 10, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310144

RESUMO

Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable Haemophilus influenzae (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (n = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, P < 0.05) and reductions in alpha diversity (q < 0.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (P < 0.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.


Assuntos
Antibacterianos , Otite Média , Animais , Criança , Humanos , Antibacterianos/uso terapêutico , Chinchila , Padrão de Cuidado , Otite Média/tratamento farmacológico , Orelha Média/patologia , Biofilmes , Nasofaringe/patologia
13.
J Pediatric Infect Dis Soc ; 13(3): 203-210, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38314853

RESUMO

BACKGROUND: Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production. METHODS: 205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE). RESULTS: 8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05). CONCLUSIONS: Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria.


Assuntos
Amoxicilina , Otite Média , Criança , Humanos , Lactente , Amoxicilina/uso terapêutico , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Antibacterianos/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , beta-Lactamases , Doença Aguda
14.
Int J Pediatr Otorhinolaryngol ; 178: 111894, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350381

RESUMO

OBJECTIVES: We report the in vivo biodistribution and ototoxicity of cationic liposomal-ceftriaxone (CFX) delivered via ear drop formulation in adult chinchilla. METHODS: CFX was encapsulated in liposomes with size of ∼100 nm and surface charge of +20 mV. 100 µl liposomes or free drug was applied twice daily in both external ear canals of adult chinchillas for either 3 or 10 days. Study groups included free ceftriaxone (CFX, Day 3: n = 4, Day 10: n = 8), liposomal ceftriaxone (CFX-Lipo, Day 3: n = 4, Day 10: n = 8), and a systemic control group (Day 3: n = 4, Day 10: n = 4). Ceftriaxone delivery to the middle ear and systemic circulation was quantified by HPLC assays. Liposome transport was visualized via confocal microscopy. Auditory brainstem response (ABR) tests and cochlear histology were used to assess ototoxicity. RESULTS: Liposomal ceftriaxone (CFX-Lipo) displayed a ∼658-fold increase in drug delivery efficiency in the middle ear relative to the free CFX (8.548 ± 0.4638% vs. 0.013 ± 0.0009%, %Injected dose, Mean ± SEM). CFX measured in blood serum (48.2 ± 7.78 ng/ml) following CFX-Lipo treatment in ear was 41-fold lower compared to systemic free-CFX treatment (1990.7 ± 617.34 ng/ml). ABR tests and histological analysis indicated no ototoxicity due to the treatment. CONCLUSION: Cationic liposomal encapsulation results in potent drug delivery across the tympanic membrane to the middle ear with minimal systemic exposure and no ototoxicity.


Assuntos
Otite Média , Ototoxicidade , Animais , Humanos , Membrana Timpânica , Chinchila , Ceftriaxona/uso terapêutico , Lipossomos/uso terapêutico , Distribuição Tecidual , Orelha Média , Otite Média/tratamento farmacológico
15.
An Pediatr (Engl Ed) ; 100(3): 173-179, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350792

RESUMO

INTRODUCTION: Recent studies show an increase in the prevalence of Haemophilus influenzae and a decrease in Streptococcus pneumoniae among the bacteria that cause acute otitis media (AOM). The objective of our study was to analyse the distribution of pathogens identified in children aged less than 14 years presenting to the emergency department with AOM and their patterns of antimicrobial resistance. PATIENTS AND METHODS: Single centre retrospective, analytical study in patients aged less than 14 years with a diagnosis of AOM in whom an ear drainage sample was collected for culture in the paediatric emergency department of a tertiary care hospital between 2013 and 2021. RESULTS: During the study period, there were 14 684 documented care episodes corresponding to children with a diagnosis of AOM. An ear drainage culture was performed in 768 of those episodes. The median age of the patients was 2 years, 57% were male and 70% had a previous history of AOM. The most frequently isolated pathogens were: Haemophilus influenzae (n = 188 [24.5%]; 15.5% of them resistant to ampicillin), Streptococcus pyogenes (n = 86 [11.2%]), Staphylococcus aureus (n = 82 [10.7%]), Streptococcus pneumoniae (n = 54 [6.9%]; 9.4% with intermediate resistance to penicillin), Pseudomonas aeruginosa (n = 42 [5.5%]) and Moraxella catarrhalis (n = 11 [1.4%]). No pathogen was isolated in 34.9% of cases. CONCLUSIONS: Haemophilus influenzae is the leading cause of AOM in children aged less than 14 years. This, combined with the low frequency of isolation and penicillin resistance of Streptococcus pneumoniae, calls into question the appropriateness of high-dose amoxicillin for empiric treatment of AOM.


Assuntos
Antibacterianos , Otite Média , Criança , Humanos , Masculino , Pré-Escolar , Feminino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Otite Média/tratamento farmacológico , Otite Média/epidemiologia , Otite Média/microbiologia , Streptococcus pneumoniae , Streptococcus pyogenes , Haemophilus influenzae
16.
Int J Pediatr Otorhinolaryngol ; 177: 111832, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38215661

RESUMO

BACKGROUND: One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured. METHODS: This was a phase 1B double-blinded randomized control trial conducted in Western Australia. Children between 6 months and 5 years undergoing VTI for bilateral middle ear effusion were recruited between 2012 and 2014 and followed for two years. Children's ears were randomized to receive either Dornase alfa (1 mg/mL) or 0.9 % sodium chloride (placebo) at time of surgery. Children were followed up at 2 weeks post-VTI and at 3-monthly intervals for 2 years. Outcomes assessed were: 1) safety and tolerability, 2) otorrhoea frequency, 3) blocked or extruded ventilation tube (VT) frequency, 4) time to blockage or extrusion, 5) time to infection recurrence and/or need for repeat VTI. RESULTS: Sixty children (mean age 2.3 years) were enrolled with 87 % reaching study endpoint. Treatment did not change otorrhoea frequency. Hearing improved in all children following VTI, with no indication of ototoxicity. Dornase alfa had some effect on increasing time until VT extrusion (p = 0.099); and blockage and/or extrusion (p = 0.122). Frequency of recurrence and time until recurrence were similar. Fourteen children required repeat VTI within the follow-up period. CONCLUSION: A single application of Dornase alfa into the middle ear at time of VTI was safe, non-ototoxic, and well-tolerated. TRIAL REGISTRATION: ACTRN12623000504617.


Assuntos
Otopatias , Otite Média com Derrame , Otite Média , Criança , Humanos , Pré-Escolar , Otite Média com Derrame/cirurgia , Otite Média/tratamento farmacológico , Otite Média/cirurgia , Desoxirribonuclease I , Orelha Média , Otopatias/cirurgia , Ventilação da Orelha Média/efeitos adversos , Cloreto de Sódio , Proteínas Recombinantes
17.
Scand J Prim Health Care ; 42(2): 237-245, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38265029

RESUMO

BACKGROUND: Antibiotic resistance is an increasing global threat, accelerated by both misuse and overuse of antibiotics. Most antibiotics to humans are prescribed in primary care, commonly for respiratory symptoms, and there is a need for research on the usage of and outcomes after antibiotic treatment to counteract antibiotic resistance. OBJECTIVE: To evaluate symptom duration, treatment length, and adverse events of antibiotic treatment in children. DESIGN AND SETTING: Observational study at four out-of-hours services and one paediatric emergency clinic in Norwegian emergency primary care. SUBJECTS: 266 children aged 0 to 6 years with fever or respiratory symptoms. MAIN OUTCOME MEASURES: Duration of symptoms and absenteeism from kindergarten/school, treatment length, and reported adverse events. RESULTS: There were no differences in duration of symptoms, fever or absenteeism when comparing the groups prescribed (30.8%) and not prescribed (69.2%) antibiotics. This lack of difference remained when analysing the subgroup with otitis media.In the group prescribed antibiotics, 84.5% of parents reported giving antibiotics for 5-7 days, and 50.7% reported no difficulties. Adverse events of antibiotics were reported in 42.3% of the cases, the vast majority being gastrointestinal disturbances. CONCLUSION: Children with fever or respiratory symptoms experience similar duration of symptoms and absenteeism regardless of antibiotic treatment. A substantial number of parents reported adverse events when the child received antibiotics. Several parents experienced additional difficulties with the treatment, some ending treatment within day 4. TRIAL REGISTRATION NUMBER: NCT02496559; Results.


Children with fever or respiratory symptoms treated at OOH services experience similar duration of symptoms or absenteeism, regardless of antibiotic treatment.Parents often choose to end antibiotic treatment prematurely due to adverse events, bad taste, or that they find treatment unnecessary.Children often experience adverse events when prescribed antibiotics, mainly gastrointestinal symptoms.


Assuntos
Otite Média , Infecções Respiratórias , Criança , Humanos , Antibacterianos/efeitos adversos , Infecções Respiratórias/tratamento farmacológico , Otite Média/tratamento farmacológico , Otite Média/induzido quimicamente , Pais , Atenção Primária à Saúde
18.
Pediatr Emerg Care ; 40(4): 283-288, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37549307

RESUMO

BACKGROUND: Penicillin or amoxicillin are the recommended treatments for the most common pediatric bacterial illnesses. Allergies to penicillin are commonly reported among children but rarely true. We evaluated the impact of reported penicillin allergies on broad-spectrum antibiotic use overall and for the treatment of common respiratory infections among treat-and-release pediatric emergency department (ED) visits. METHODS: Retrospective cohort study of pediatric patients receiving antibiotics during a treat-and-release visit at a large, pediatric ED in the northeast from 2014 to 2016. Study exposure was a reported allergy to penicillin in the electronic medical record. Study outcomes were the selection of broad-spectrum antibiotics and alternative (second-line) antibiotic therapy for the treatment of acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis. We used unadjusted and adjusted generalized estimating equation models to analyze the impact of reported penicillin allergies on the selection of broad-spectrum antibiotics. We used unadjusted and adjusted logistic regression models to determine the probability of children with a documented penicillin allergy receiving alternative antibiotic treatments for AOM and GAS. RESULTS: Among 12,987 pediatric patients, 810 (6.2%) had a documented penicillin allergy. Penicillin allergies increased the odds of children receiving a broad spectrum versus narrow spectrum antibiotic (adjusted odds ratio, 13.55; 95% confidence interval (CI), 11.34-16.18). In our adjusted logistic regression model, the probability of children with a documented penicillin allergy receiving alternative antibiotic treatment for AOM was 0.97 (95% CI, 0.94-0.99) and for GAS was 0.97 (95% CI, 0.92-0.99). CONCLUSIONS: Antibiotic stewardship efforts in pediatric EDs may consider the delabeling of penicillin allergies particularly among children receiving antibiotics for an acute respiratory infection as a target for intervention.


Assuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Otite Média , Criança , Humanos , Antibacterianos/efeitos adversos , Estudos Retrospectivos , Visitas ao Pronto Socorro , Penicilinas/efeitos adversos , Serviço Hospitalar de Emergência , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/tratamento farmacológico , Progressão da Doença , Otite Média/tratamento farmacológico
19.
Ann Otol Rhinol Laryngol ; 133(1): 37-42, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37386844

RESUMO

OBJECTIVE: To examine the relationship between conferred immunity after standard pneumococcal series and refractory otolaryngologic infections in pediatric patients using post-vaccination antibody titers, and to identify contributory underlying conditions revealed when vaccination/re-vaccination fails to confer protective immunity. STUDY DESIGN: IRB-reviewed and "exempt" retrospective case series with chart review using the Epic® Electronic Medical Record system from 2013 to 2021. SETTING: Dedicated tertiary referral children's hospital. METHODS: Pneumococcal antibody titer results were assessed for children ages 0 to 21 years and: (1) at least 1 of 7 otolaryngologic disease diagnoses and (2) having received the 4-dose schedule of pneumococcal conjugate vaccine (PCV 7 or 13). RESULTS: A total of 241 subjects met inclusion criteria with 356 laboratory tests. Recurrent acute otitis media, chronic rhinitis, and chronic otitis media with effusion were the 3 most frequent diagnoses. At presentation, only 27.0% of subjects had titers conferring immunity from their prior vaccinations with PCV. About 85 subjects had been subsequently revaccinated with Pneumococcal Polysaccharide Vaccine (PPSV), and antibody responses conferring immunity reached 91.8%. Seven subjects never developed adequate responses; 5 of these had recurrent acute otitis media as the primary otolaryngologic diagnosis. Secondary "revealed" diagnoses included Juvenile Rheumatoid Arthritis (n = 1), unresolved specific antibody deficiency (n = 2), and Hypogammaglobulinemia (n = 1). CONCLUSION: In pediatric patients with recurrent infectious otolaryngologic disease refractory to traditional medical and surgical therapy, inadequate responses to pneumococcal vaccination may be revealed. This correlation represents a potential pathway for diagnosis and therapy.


Assuntos
Otite Média , Infecções Pneumocócicas , Vacinas Pneumocócicas , Criança , Humanos , Otite Média/tratamento farmacológico , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/tratamento farmacológico , Vacinas Pneumocócicas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Streptococcus pneumoniae , Vacinação
20.
Pediatr Emerg Care ; 40(4): 265-269, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37195689

RESUMO

OBJECTIVE: Urgent care (UC) clinicians frequently prescribe inappropriate antibiotics for upper respiratory illnesses. In a national survey, pediatric UC clinicians reported family expectations as a primary driver for prescribing inappropriate antibiotics. Communication strategies effectively reduce unnecessary antibiotics while increasing family satisfaction. We aimed to reduce inappropriate prescribing practices in otitis media with effusion (OME), acute otitis media (AOM), and pharyngitis in pediatric UC clinics by a relative 20% within 6 months using evidence-based communication strategies. METHODS: We recruited participants via e-mails, newsletters, and Webinars from pediatric and UC national societies. We defined antibiotic-prescribing appropriateness based on consensus guidelines. Family advisors and UC pediatricians developed script templates based on an evidence-based strategy. Participants submitted data electronically. We reported data using line graphs and shared deidentified data during monthly Webinars. We used χ 2 tests to evaluate change in appropriateness at the beginning and end of the study period. RESULTS: The 104 participants from 14 institutions submitted 1183 encounters for analysis in the intervention cycles. Using a strict definition of inappropriateness, overall inappropriate antibiotic prescriptions for all diagnoses trended downward from 26.4% to 16.6% ( P = 0.13). Inappropriate prescriptions trended upward in OME from 30.8% to 46.7% ( P = 0.34) with clinicians' increased use of "watch and wait" for this diagnosis. Inappropriate prescribing for AOM and pharyngitis improved from 38.6% to 26.5% ( P = 0.03) and 14.5% to 8.8% ( P = 0.44), respectively. CONCLUSIONS: Using templates to standardize communication with caregivers, a national collaborative decreased inappropriate antibiotic prescriptions for AOM and had downward trend in inappropriate antibiotic prescriptions for pharyngitis. Clinicians increased the inappropriate use of "watch and wait" antibiotics for OME. Future studies should evaluate barriers to the appropriate use of delayed antibiotic prescriptions.


Assuntos
Otite Média , Faringite , Infecções Respiratórias , Criança , Humanos , Antibacterianos/uso terapêutico , Faringite/tratamento farmacológico , Otite Média/tratamento farmacológico , Prescrição Inadequada/prevenção & controle , Comunicação , Instituições de Assistência Ambulatorial , Padrões de Prática Médica , Infecções Respiratórias/tratamento farmacológico
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