In the name of God

1. In the name of God Judicious Antibiotic Therapy for Upper Respiratory Tract Infections in Pediatrics Dr. Hamid Rahimi Pediatric Infectious Disease Specialist

2. References Principles of Judicious Antibiotic Prescribing for Upper Respiratory Tract Infections in Pediatrics – Pediatrics 2013 Clinical Practice Guideline for the Diagnosis and Management of Acute Bacterial Sinusitis in Children Aged 1 to 18 Years – Pediatrics 2013 The Diagnosis and Management of Acute Otitis Media - Pediatrics 2013 Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America - Clinical Infectious Diseases 2012

3. More than 1 in 5 pediatric ambulatory visits to a physician result in an antibiotic prescription. As many as 20% of antibiotic prescriptions are directed toward respiratory conditions for which they are unlikely to provide benefit. Recent evidence shows that broad-spectrum antibiotic prescribing has increased and frequently occurs when either no therapy is necessary or when narrower-spectrum alternatives are appropriate.

4. Such overuse of antibiotics causes avoidable drug-related adverse events, contributes to antibiotic resistance, and adds unnecessary medical costs. This is compounded by the fact that few new antibiotics to treat antibiotic-resistant infections are under development.

5. Principles of Judicious Antibiotic Prescribing for Upper Respiratory Tract Infections in Pediatrics • Principle 1: Determine the likelihood of a bacterial infection • Principle 2: Weigh benefits versus harms of antibiotics • Principle 3: Implement judicious prescribing strategies

6. Principle 1: Determine the likelihood of a bacterial infection Many aspects of the clinical history, symptoms, and signs of bacterial URIs overlap with or mirror those of viral infections or noninfectious conditions. In the specific cases of AOM, acute bacterial sinusitis, and pharyngitis, there are well-established stringent criteria that aid in distinguishing bacterial from nonbacterial causes.

7. Principle 2: Weigh Benefits Versus Harms of Antibiotics • If a bacterial infection is determined to be likely, the next step is to compare the evidence about the benefits of antibiotic therapy for each condition to the potential for harms. • Relevant outcomes to consider for benefits include • Cure rate • Symptom reduction • Prevention of complications, and secondary cases • Outcomes for harms include • Antibiotic-related adverse events (eg, abdominal pain, diarrhea, rash), • Clostridium difficilecolitis • Development of resistance • Cost

8. Principle 3: Implement Judicious Prescribing Strategies • When evidence suggests that antibiotics may provide benefit, several aspects of judicious prescribing should be considered. • Selecting an appropriate antibiotic agent that treats the most likely pathogens • Selecting the appropriate dose • Treating for the shortest duration required • Considering the role of observation and use of delayed prescribing strategies.

9. Acute Otitis Media

10. Acute Otitis Media • The most common infection for which antibacterial agents are prescribed for children in the US • 1/3 of office visits to pediatricians

11. Key Action Statements 1 Diagnosis of AOM • Acute purulent otorrhea is present and otitis externa has been excluded • Moderate to severe bulging of the TM • Mild bulging of the TM and … • Recent (less than 48 hours) onset of ear pain (holding, tugging, rubbing of the ear in a nonverbal child) or • Intense erythema of the TM

12. Key Action Statements 1 Diagnosis of AOM • Clinicians should not diagnose AOM in children who do not have MEE (based on pneumatic otoscopy and/or tympanometry).

13. Normal TM

14. Moderate Bulging Severe Bulging

15. Signs of middle-ear inflammation Mild bulging with intense erythema of the TM

16. Established acute otitis media

17. Predictive value of combinations of otoscopic findings in children with acute ear symptoms

18. Differential diagnosis • Other conditions  • Redness of tympanic membrane • AOM • Crying • Upper respiratory infection with congestion and inflammation of the mucosa lining the entire respiratory tract • Trauma and/or cerumen removal • Decreased or absent mobility of tympanic membrane • AOM and OME • Tympanosclerosis • A high negative pressure within the middle ear cavity • Ear pain • Otitis externa • Ear trauma • Throat infections • Foreign body • Temporomandibular joint syndrome

19. Management • NNT (Number Need to Treat)

20. NNT in AOM forAntibiotic therapy vs. control groups Rovers MM, Glasziou P, Appelman CL, et al. Antibiotics for acute otitis media: an individual patient data meta-analysis. Lancet. 2006;368(9545):1429–1435

21. NNT in AOM forantibiotic therapy vs. control groups • Antibiotics produced a small reduction in the number of children with pain 2 to 7 days after diagnosis. • They also concluded that most cases spontaneously remitted with no complications (NNT = 16). • Antibiotics were most beneficial in children younger than 2 years with bilateral AOM and in children with otorrhea. Sanders S, Glasziou PP, DelMar C, Rovers M. Antibiotics for acute otitis media in children [review]. Cochrane Database Syst Rev. 2009;(2):1–43

22. Observation Option OR Wait & See protocol • Observation without use of antibacterial agents in a child with uncomplicated AOM is an option for selected children In this protocol … • Deferring antibacterial treatment of selected children for 48 -72 hrs & limiting management to symptomatic relief

23. Key Action Statements 3 Management of AOM - Antibiotic Rx • The clinician should prescribe antibiotic therapy for … • AOM (bilateral or unilateral) in children 6 months and older with severe signs or symptoms (ie, moderate or severe otalgia or otalgia for >48 hours, or Temp ≥ 39°C) • Bilateral AOM in children younger than 24 months without severe signs or symptoms. • AOM in infant ≤6 months old

24. Key Action Statements 3 Management of AOM – Observation vs. Antibiotic Rx • The clinician should either prescribe antibiotic therapy or offer observation with close follow-up based on joint decision-making with the parent(s)/caregiver for • Unilateral AOM in children 6 months to 23 months of age without severe signs or symptoms. • AOM (bilateral or unilateral) in children 24 months or older without severe signs or symptoms.

25. Key Action Statements 3 Management of AOM – Observation vs. Antibiotic Rx • When observation is used, a mechanism must be in place to ensure follow-up and begin antibiotic therapy if the child worsens or fails to improve within 48 to 72 hours of onset of symptoms.

26. Observation • Observation is only appropriate when … Follow-up can be ensured and antibiotic therapy initiated if symptoms persist or worsen • Specific follow-up system i.e. • Reliable parent / caregiver • Convenient obtaining medications if necessary

27. Observation • Antibiotics should be prescribed when the patient does not improve with observation for 48 to 72 hours • Adequate follow-up may include … 1 - A parent-initiated visit or phone contact if symptoms worsen or do not improve at 48 -72 hrs 2 - A scheduled follow-up appointment in 48 -72 hrs 3 - Giving parents an antibiotic prescription that can be filled if illness does not improve in this time frame. “wait-and-see prescription” (WASP)

28. Selecting Effective antibiotic

29. Key Action Statements 4 Selecting Effective antibiotic • Clinicians should prescribe amoxicillin for AOM when a decision to treat with antibiotics has been made. • Clinicians should prescribe an antibiotic with additional β-lactamase coverage for AOM when child • Has received amoxicillin in the past 30 days • Has concurrent purulent conjunctivitis • Has a history of recurrent AOM unresponsive to amoxicillin.

33. Macrolides & Cefixime • Macrolides, such as erythromycin and azithromycin, have limited efficacy against both H influenzae and S pneumoniae. • Cefiximehas limited efficacy against S pneumoniae • In last AAP recommendation notrecommended for treatment of AOM.

34. Ceftriaxone Although a single injection of ceftriaxone is approved by the US FDA for the treatment of AOM, Results of a double tympanocentesis study (before and 3 days after single dose ceftriaxone) suggest that more than 1 ceftriaxone dose may be required to prevent recurrence of the middle ear infection within 5 to 7 days after the initial dose.

35. Clindamycin ±3rd Generation Cephalosporin • Clindamycin alone (30–40 mg/kg per day in 3 divided doses) may be used for suspected penicillin-resistant S pneumoniae; however, the drug will likely not be effective for the multidrug-resistant serotypes. • Clindamycin lacks efficacy against H influenzae.

36. Key Action Statements 4 Selecting Effective antibiotic • Clinicians should reassess the patient ifthe caregiver reports that the child’s symptoms have worsened or failed to respond to the initial antibiotic treatment within 48 to 72 hours and determine whether a change in therapy is needed.

37. Duration of therapy • For children younger than 2 y/o and severe disease, a standard 10-day course is recommended • A 7-day course of oral antibiotic appears to be equally effective in children 2 to 5 years of age with mild or moderate AOM. • For children ≥ 6 years of age with mild to moderate disease 5 -7 days is appropriate

38. Follow-up of the Patient With AOM • There is little scientific evidence for a routine 10- to 14-day reevaluation visit for all children with an episode of AOM. • The physician may choose to reassess some children, such as young children with severe symptoms or recurrent AOM or when specifically requested by the child’s parent.

39. Antibiotic therapy in Treatment Failure

40. Microbiology of AOM

41. Predicted treatment failure rates based on PD breakpoints for expected pathogens in low- or high-risk AOM

42. Predicted treatment failure rates based on PD breakpoints for expected pathogens in low- or high-risk AOM

43. In daily clinical practice… Amoxicillin - Clavul. 90mg/kg Ceftriaxone ×1 – 3 dose Clindamycin + Cefixime Amoxicillin 90mg/kg Azithromycin Clarithromycin Cefixime Cotri-Erythro Cefuroxime Amoxicillin - Clavul.30mg/kg Amoxicillin 30 – 45 mg/kg

44. For getting a ratio of amoxicillin to clavulanate of 14:1 • Co-Amoxiclave + Amoxicillin 156/325 125/250 1/3 2/3 • Farmentin BD + Faramox 228/456 200/400 1/2 1/2

45. In daily clinical practice… • Month of year ( mehr vs. farvardin) • Previous antibacterial treatment

46. In daily clinical practice…

47. In daily clinical practice… • Previous (First line) antibacterial treatment Failure Amoxicillin - Clavul. 90mg/kg Amoxicillin 30mg/kg Azithromycin Cefixime Cotri-Erythro Cefuroxime Azithromycin Clarithromycin Cefixime Cotri-Erythro Cefuroxime Amoxicillin - Clavul. 30mg/kg Amoxicillin - Clavul. 90mg/kg Amoxicillin 90mg/kg

48. Acute Bacterial Sinusitis

49. Scope of Problem • 3rd most common diagnosis for which antibiotics are prescribed • Abnormalities of the paranasal sinuses are common during the course of an uncomplicated cold (up to 87%). • Viral URIs   secondary bacterial sinusitis • 0.5 -2% in adults & 5% in children

50. Classification of Bacterial Sinusitis • Acute bacterial sinusitis (ABS) • Infection lasting < 30 days, symptoms resolve completely • Subacute bacterial sinusitis • Infection lasting between 30-90 days, yet resolves completely • Recurrent • Episodes of <30 days duration with intervals of 10 days without symptoms >3 episodes in a 6-month period, or >4 episodes in one year • Each episodes respond briskly to antibiotic therapy • Chronic sinusitis • Symptoms lasting >90 days • Some guidelines add treatment failure + a positive imaging study