Acute Otitis Media (AOM) Pharm 221 F2024 PDF

Acute Otitis Media PHARM 221 F2024 Brett Barrett Learning Objectives 1. Describe the etiology, pathophysiology, and diagnosis of acute otitis media (AOM). 2. Discuss the rationale for antimicrobial therapy in the management of AOM. 3. Explain the impact of routine childhood vacci...

Acute Otitis Media PHARM 221 F2024 Brett Barrett Learning Objectives 1. Describe the etiology, pathophysiology, and diagnosis of acute otitis media (AOM). 2. Discuss the rationale for antimicrobial therapy in the management of AOM. 3. Explain the impact of routine childhood vaccination on AOM incidence and microbiology. 4. Recognize patients with AOM who might benefit from anti‐infective therapy. 5. Identify DTPs in patients presenting with AOM and design a patient‐focused careplan to address those. Resources Le Saux N, Robinson JL; Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Management of acute otitis media in children six months of age and older. Paediatr Child Health. 2016;21(1):39‐50. doi:10.1093/pch/21.1.39 Choosing Wisely Canada. Antibiotics for ear infections in children: When you need them and when you don’t. Available at: https://choosingwiselycanada.org/pamphlet/childr en‐ear‐infections/ Etiology and Pathophysiology of AOM  Recall: Anatomy of the Ear Modified from http://printer‐friendly.adam.com/content.aspx?productId=117andpid=1andgid=007010andc_custid=758; accessed 10‐11‐19.  Important Definitions Middle ear effusion (MEE): fluid in middle ear Otalgia: pain in ear Fluid buildup Otorrhea: due to discharge from ear narrowing of Eustachian tube Modified from http://printer‐friendly.adam.com/content.aspx?productId=117andpid=1andgid=007010andc_custid=758; accessed 10‐11‐19. Clinical Syndromes due to MEE Otitis media with effusion (OME) MEE without evidence of infection/ inflammation E.g., due to allergies, URTI, smoking Muffled hearing, feeling of fullness Can be chronic, can persist after resolution of AOM Acute otitis media (AOM) MEE with signs and/ or symptoms of middle ear inflammation due to infection Rapid onset with signs of illness  Pathophysiology of AOM Obstruction of Eustachian tube Allergies or viral URTI cause congestion of respiratory mucosa Accumulation of secretions in the middle ear i.e., middle ear effusion If bacteria or viruses are present, they multiply and cause inflammation Pathogens travel through Eustachian tube from upper respiratory tract Following resolution of acute infection, middle ear effusion can persist for weeks to months  Risk Factors for AOM – I Age Highest incidence from 6 to 18 mos Acquire viral infections more often Immature anatomy and immune response Recurrent AOM more likely if first episode before 6 mos Modified from https://www.salinetherapy.com/wp‐content/uploads/2014/03/Eustachian‐tube.jpg; accessed 10‐11‐19. Risk Factors for AOM – II Modifiable Non‐modifiable Bottle feeding Daycare Breastfeeding for > 3 mos is Indigenous peoples protective Breastfeeding results in Season (fall/ winter) decreased nasopharyngeal bacterial colonization Family history of AOM Position of infant when feeding Orofacial abnormalities Facial musculature development Immunological impairment Immunological factors in breastmilk Pacifier use 80 to 90% get at least one episode by 3 yrs Smoke/ pollution Incidence decreases after 2 yrs, with another peak around 5 to 6 yrs (why?)  Clinical and Economic Impacts of AOM Significant disease burden in < 5 yrs of age 1/3 of physician visits Most frequent diagnosis Most frequent reason for antimicrobial therapy Significant economic impact1 Time lost from work and school ~40% of cases result in work absenteeism, with avg 16 hrs lost High use of healthcare resources Episode estimated to cost $321 80% of which borne by family Negative impact of parental stress and family functioning 1Dube E et al. Can Fam Phys. 2011;57(1):60‐65. Diagnosis of AOM Systematic Approach to ID Pharmacotherapy IESA Something they Indicated Effective Safe can Adhere to Is there evidence of infection? If so, does it require treatment? AOM Symptoms Rapid development (< 48 hrs, often overnight) Otalgia (due to local inflammation) Most common symptom Best predictor of AOM Decreased hearing, sense of fullness (due to MEE) Balance problems occasionally Fever (due to systemic inflammation) Usually < 40 Only occurs in 1/3 to 2/3  Difficult patient population to assess! Young children and infants cannot articulate symptoms, so presentation may be non‐specific (e.g., irritability/ excessive crying, apathy, disturbed or restless sleep, poor feeding, ear rubbing or pulling). Clinical dx must be confirmed with visualization of tympanic membrane (TM).  Pneumatic Otoscopy of TM Normal Abnormal Translucent Opaque Pearl‐grey White, yellow, Moves with or, if inflamed, insufflation of pink/ red air Decreased/ absent mobility http://otoscopy.hawkelibrary.com/albums/album08/Inst_4.jpg; accessed 10‐11‐19. https://pbs.twimg.com/media/CJMboIeWsAAjQgd.png; accessed 10‐11‐19. Diagnosis of AOM requires: 1. Signs/ symptoms of middle ear inflammation Bulging TM, erythema of TM, otalgia, OR fever AND 2. Evidence of middle ear effusion TM opacity, decreased/ absent TM mobility, OR otorrhea Complications: TM Rupture Relieves pressure  acute pain relief Usually heals quickly (hrs to days) More likely to occur in bacterial infection  Complications Mastoiditis Pus fills air cells of mastoid bone Pain or swelling Inflammation on CT Other complications rare in developed countries Meningitis Brain abscess http://cdn.ent‐surgery.com.au/wp‐content/uploads/2014/07/mastoid.jpg; accessed 10‐11‐19. http://image1.slideserve.com/2185186/acute‐mastoiditis‐n.jpg; accessed 10‐11‐19. Systematic Approach to ID Pharmacotherapy IESA Something they Indicated Effective Safe can Adhere to Is there evidence of infection? If so, does it require treatment? AOM is frequently self‐limiting Both viral and bacterial pathogens can cause AOM S. pneumoniae, non‐typeable H. influenzae, M. catarrhalis, rarely Group A Streptococcus In most cases, both bacteria and viruses are present Regardless of etiology, 80% of untreated children experience symptom resolution within 3 days Spontaneous resolution more likely with less virulent bacteria (e.g., M. catarrhalis, H. influenzae) Severe complications rare (e.g., 0.17% mastoiditis) Venekamp RP, Sanders SL, Glasziou PP, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2023;11(11):CD000219. Published 2023 Nov 15. doi:10.1002/14651858.CD000219.pub5 Management of AOM Watchful Waiting/ Delayed Prescribing Recommended for patients ≥ 6 mos who: Have mild disease; Have had symptoms less than 48 hrs; AND, Do not have TM perforation or other complications E.g., immunodeficiency, craniofacial abnormalities, tympanostomy tubes, cochlear implants, etc. Mild disease defined as: Mild or moderately bulging tympanic membrane; AND, Mildly ill (alert, fever < 39 responding to antipyretics, mild otalgia) Le Saux N, Robinson JL. Paediatr Child Health. 2016;21(1):39‐44. Implementing Watchful Waiting Caregiver education is essential for success 1. Rationale: decreased antimicrobial use ~ 60 to 70% do not fill Rx 2. Safety: not associated with increased pain, frequency of TM perforation, or recurrence 3. Reasons to start therapy: Symptoms do not improve within 24 to 48 hrs; OR Development of severe symptoms at any time (i.e., fever ≥ 39 ℃, severe otalgia, etc.) If Rx is not filled immediately, ensure timely access  ALL patients need good analgesia! Caregivers tend to be cautious Give only when absolutely necessary, dose conservatively Concerns re: adverse effects, lack of clear instructions Essential component of careplan, regardless of antimicrobial strategy Pain often only cursorily mentioned in AOM visit Strongly consider regularly scheduled administration for first 24 to 48 hrs Analgesic Options – I Most have not been well studied in AOM specifically Topical lidocaine or benzocaine (Auralgan®) Efficacy: reduces pain compared with placebo, duration is short‐lived Safety: should not be used in TM perforation or children < 2 yrs Adherence: requires frequent administration (q1 to 2 hrs PRN) Analgesic Options – II Systemic acetaminophen or ibuprofen Recall: safety and adherence in management of fever Efficacy for pain: both more effective than placebo in AOM (but no direct comparison between two) Acetaminophen 10 to 15 mg/kg PO q4 to 6 hr Ibuprofen 5 to 10 mg/kg PO q6 to 8 hr Generally not recommended: narcotics, distraction, external application of heat or cold, olive oil, herbal extracts, homeopathy Systematic Approach to ID Pharmacotherapy IESA Something they Indicated Effective Safe can Adhere to What pathogen(s) do we need to cover? Is our antimicrobial therapy empiric or targeted? Is that antimicrobial EFFECTIVE/ LIKELY TO BE EFFECTIVE? Empiric Therapy Targeted Therapy Requires educated guess about what No need to “guess” what pathogen is pathogens are likely present present, nor what it is susceptible to 1. What does the literature say are the common pathogens for this infection in my patient? 2. Has my patient been exposed to anything I need to worry about? 3. Can I guess anything about what my patient might be colonized with? 4. How much resistance is likely in my patient? 5. Do I have to cover ALL of these pathogens in my patient? Is that antimicrobial LIKELY TO BE EFFECTIVE? – I 1. What does the literature say are the common pathogens for this infection in my patient? S. pneumoniae, non‐typeable H. influenzae, M. catarrhalis, rarely Group A Streptococcus H. influenzae and M. catarrhalis more likely when concomitant purulent conjunctivitis Group A Streptococcus more likely when TM perforation and otorrhea present 2. Has my patient been exposed to anything I need to worry about? Likely not relevant Is that antimicrobial LIKELY TO BE EFFECTIVE? – I 3. Can I guess anything about what my patient might be colonized with? Impact of immunization on circulating bacteria (i.e., herd immunity) more important than individual patient’s vaccination status H. influenzae type B conjugated vaccine added in 1990’s Hib does not cause AOM but rather bacterial meningitis S. pneumoniae conjugated vaccines 7‐valent in 2000, 10‐valent in 2010, 13‐valent in 2011, 15‐ valent in 2022 S. pneumoniae causes AOM plus a variety of invasive illnesses  Increased proportion of non‐typeable H. influenzae and non‐vaccine serotypes of S. pneumoniae https://www.canada.ca/en/public‐health/services/publications/vaccines‐immunization/national‐advisory‐committee‐immunization‐ recommendations‐public‐health‐programs‐use‐pneumococcal‐vaccines‐children‐including‐use‐15‐valent‐20‐valent‐conjugate‐vaccines.html; accessed 03‐11‐24. Is that antimicrobial LIKELY TO BE EFFECTIVE? – II 4. How much resistance is likely in my patient? Recall: patient‐specific risk factors for S. pneumoniae resistance: recent antimicrobial use, daycare, < 2 yrs Recall: ~ 50% of H. influenzae and 100% of M. catarrhalis produce beta‐lactamase 5. Do I have to cover ALL of these pathogens in my patient? No! For most patients, focus on S. pneumoniae and non‐ beta‐lactamase‐producing H. influenzae These are most common and, for S. pneumoniae, least likely to resolve spontaneously  All patients should receive therapy with good activity against S. pneumoniae and non‐beta‐ lactamase‐producing H. influenzae Tympanic membrane perforation and otorrhea? Add GAS (if not already covered) Concomitant purulent conjunctivitis? Add beta‐lactamase‐producing H. influenzae and M. catarrhalis Failed amoxicillin? Focus on beta‐lactamase‐producing pathogens Amoxicillin Preferred for most patients Effective against most strains of S. pneumoniae, especially when dosed appropriately, and ~ 50% of H. influenzae Use high‐dose if risk factors for resistance Penetrates area and has most evidence for use Safe in most patients Few serious toxicities, all ages/ pregnancy, low collateral damage Something patients can adhere to Amoxicillin Dosing for S. pneumoniae Regular: 40 mg/kg/day PO ÷ TID High: 90 mg/kg/day PO ÷ BID FYI only: ranges given for AOM Regular: 500 mg po TID High: 1000 mg po TID FYI: AOM uncommon in teens/ adults Amoxicillin‐Clavulanic Acid 1. Patients who present with purulent conjunctivitis H. influenzae and M. catarrhalis more likely If slow to resolve, culture conjunctival discharge (i.e., targeted therapy) 2. Patients who fail amoxicillin (i.e., symptoms not improved within 24 hrs and resolved within 3 days) If given high‐dose amoxicillin initially, now concerned about beta‐lactamase‐producing pathogens If given regular‐dose amoxicillin initially, unclear whether issue is beta‐lactamase‐producing pathogens or intermediate‐ penicillin‐resistant‐S. pneumoniae 3. Patients who have taken amoxicillin in past 30 days More concerned about beta‐lactamase‐producing pathogens as part of normal flora  * Use 7:1 ratio to minimize diarrhea due to clavulanic acid; recommended to limit clavulanic dose to < 10 mg/kg/day Amox‐Clav Dosing for S. pneumoniae Regular: 45 mg/kg/day* PO ÷ BID to TID High: above PLUS plain amoxicillin 45 mg/kg/day PO ÷ BID to TID 500 mg po TID or 875 mg po BID  (e.g., side chains) https://data‐spectrum‐md.s3.amazonaws.com/uploads/document/230/615/90ca2129‐bcb8‐4960‐9344‐5912cccee512.pdf; accessed 19‐10‐23. Alternative Efficacy Safety Adherence Cefuroxime Covers all pathogens, BID, poor palatability inferior to amoxicillin for Cefprozil S. pneumoniae BID, good palatability Clarithromycin Covers all pathogens, with More collateral damage BID, poor palatability moderate risk for S. May drive more resistance Once daily, good Azithromycin pneumoniae and GAS in S. pneumoniae, more palatability, only requires resistance collateral damage 3 to 5 days of therapy Covers GAS and S. pneumoniae, but not H. Greater risk for C. difficile Clindamycin TID, poor palatability influenzae or M. infection catarrhalis Covers all pathogens with very little risk for Significant risk for C. resistance difficile infection and Once daily, only requires 3 Ceftriaxone collateral damage, days of therapy, but IM/ IV Reserved for amoxicillin‐ additional IV‐related clavulanic acid treatment adverse effects failure Duration of Therapy In children ≥ 2 years with uncomplicated disease 5 days is as effective as 10 days (with fewer side effects) 10 days required for < 2 years Perforated TM Failure of initial therapy Follow‐Up Monitoring All should be offered analgesic and/ or antipyretics Timeframe for evaluating effectiveness of these will be shorter than for antimicrobial Evaluating effectiveness of antimicrobial therapy Symptoms/ need for symptomatic therapy should improve within 24 hrs and resolve within 3 days MEE +/‐ associated symptoms may persist for months despite resolution of infection Prevention Handwashing Limit pacifier use Encourage breast feeding Minimize time spent in daycare Avoid exposure to second hand smoke Vaccination (influenza, COVID‐19, pneumococcal) Recurrent AOM (rAOM) Recurrent AOM ≥ 3 distinct episodes within 6 mos or ≥ 4 in 12 mos Usually resolves with age (i.e., 3 to 4 yrs) More likely in those who experience first episode before 6 mos or who have siblings with rAOM Approaches to management: 1. Treat episodes as they occur 2. Tympanostomy tubes 3. Antimicrobial prophylaxis  1. Treat episodes as they occur Best for older kids, those with only modifiable risk factors, where there’s less burden to family, and no concern re: language development 2. Tympanostomy tubes Allows drainage of middle ear fluid  decreased pain of AOM episodes, may decrease frequency (but limited evidence) Inferior to antimicrobial prophylaxis in one trial Small study, modest benefit, performed before PCV http://www.kidshealth.org.nz/sites/kidshealth/files/images/Grommet_photo.jpg; accessed 11‐11‐19. 3. Antimicrobial prophylaxis Significant decrease in episodes compared with placebo (i.e., 20 to 50% fewer, NNT = 5) Rates return to baseline after discontinuation Must consider antibiotic harms Most appropriate in younger kids with non‐modifiable risk factors, who experience more severe episodes (incl. repeated TM ruptures), and where there’s significant impact on family or concerns re: developmental and language delays Antimicrobial Therapy for rAOM Treatment x 10 days No antimicrobial therapy in past 4 to 6 wks  amoxicillin (high‐dose if risk factors) Recent antimicrobial therapy or amoxicillin prophylaxis  amoxicillin‐clavulanic acid Tympanostomy tube otorrhea Due to AOM or infection from contaminated water Resolves spontaneously within 14 days in ~ 50% If unwilling to wait: antibiotic +/‐ steroid otic drops x 5 to 7 days (if no systemic symptoms, immunocompromise)  What questions do you have? 1. Describe the etiology, pathophysiology, and diagnosis of acute otitis media (AOM). 2. Discuss the rationale for antimicrobial therapy in the management of AOM. 3. Explain the impact of routine childhood vaccination on AOM incidence and microbiology. 4. Recognize patients with AOM who might benefit from anti‐infective therapy. 5. Identify DTPs in patients presenting with AOM and design a patient‐focused careplan to address those.