1 上呼吸道感染 抗生素使用原則 小兒感染科 趙雁南醫師 / 邱南昌醫師, 李聰明醫師

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3 Antibiotic usage in primary care units in Taiwan (Chang SC et al Diag Micro Infect Dis 2001;40: 137-43) 1996 ~ 1999, collect prescriptions for 1 wk in March each year, sampled from 114~166 health stations with 40891 ~ 53992 physician-visits each year Antibiotic Tx in 13.4% of total visits Patients < 11 y/o highest (38.2%) percentage Common cold most frequent (32%) diagnosis for antibiotic prescription Among patients with the Dx of common cold, antibiotic Tx in 31%, highest among < 16 y/o (45.5%) Penicillin class 35%, cephalosporins 27%, macrolides 22%, others

4 Six common diagnoses in which antibiotics were prescribed Six common diagnoses in which antibiotics were prescribed Chang SC et al Diag Micro Infect Dis 2001;40:137-43 DiagnosisNo. of patients-visits with antibiotics prescribed % of total antibiotic prescriptions Common cold1358832.3 COPD or asthma24085.7 Acute bronchitis21275.1 Skin and soft tissue infections 17814.2 Acute tonsillitis9992.4 Cystitis9292.2

5 Proportion (%) of patient-visits resulting in antibiotic prescription Proportion (%) of patient-visits resulting in antibiotic prescription Chang SC et al Diag Micro Infect Dis 2001;40:137-43 Diagnosis Age group (years)  15 16-64  65 Total Common cold45.531.523.131.3 Influenza52.221.529.133.2 COPD or asthma 44.327.019.523.2

6 Prevalence of antimicrobial resistance of common RTI pathogens isolated from 12 major Hospital in Taiwan, 2000 Penicillin-nonsusceptible S. pneumoniae 60~80% Erythromycin-resistant S. pneumoniae 67~100% Ampicillin-resistant H. influenzae 45~73% Erythromycin-resistant beta-hemolytic streptococcus 30~51% Methicillin-resistant S. aureus 53~83% (Hsueh PR et al Emerg Infect Dis 2002;8:132-7)

7 為了減少門診抗生素不當使用之情形，健保局 於民國 90 年 2 月 1 日開始施行上呼吸道感染抗生 素使用之給付規定，明確規定 “ 上呼吸道感染 如屬一般感冒（ common cold ）或病毒性感染 者，不應使用抗生素 ” 。 在 90 年 2 月之前的上呼吸道感染病人平均每月 抗生素使用率為 49.5% ， 90 年 2 月之後則降為 24.1% 。 研究人員：張上淳 執行期間： 91 年 11 月 11 日至 92 年 2 月 10 日

8 Guidelines for antimicrobial therapy of acute upper respiratory tract infection in Taiwan Seven acute URTI chosen: acute sinusitis, acute otitis media, acute pharyngotonsillitis, acute epiglotittis, acute bronchitis, common cold, influenza Principles of guidelines From the viewpoint of primary care physicians Antimicrobial agents suggested marketing in Taiwan Based on local epidemiologic data and antimicrobial resistant rate of pathogens Antimicrobial agents suggested mainly oral formulation

9 Guidelines for antimicrobial therapy of acute URT in Taiwan 診 斷首 選另 選 急性鼻竇炎 (Acute sinusitis) Amoxicillin (high dose) Ampicillin Amoxicillin/clavulanate Ampicillin/sulbactam 2 o or 3 o cephalosporins (oral) 急性中耳炎 (Acute otitis media) Amoxicillin (high dose) Ampicillin Amoxicillin/clavulanate Ampicillin/sulbactam 2 o or 3 o cephalosporins (oral) 急性咽扁桃腺炎 (Acute pharyngotonsillitis) Penicillin V Benzathine penicillin (IM) Clindamycin Macrolides 1o cephalosporins 急性支氣管炎 (Acute bronchitis) ---- 感冒 (Common cold) ----

10 Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults Annals of Internal Medicine. March 20, 2001 Nonspecific Upper Respiratory Tract Infections Acute Rhinosinusitis Acute Pharyngitis Uncomplicated Acute Bronchitis

11 Appropriate Abx Use for Tx of Nonspecific URTI in Adults Recommendation 1. The diagnosis of URTI should be used to denote an acute infection that is typically viral in origin and in which sinus, pharyngeal, and lower airway symptoms, although frequently present, are not prominent [B] greatest concentration of virus in the nasal secretions: sneezing, nose blowing, contamination with nasal secretions

12 Appropriate Abx Use for Tx of Nonspecific URTI in Adults Recommendation 2. Antibiotic treatment of adults with nonspecific upper respiratory tract infection does not enhance illness resolution and is not recommended [A].

13 Appropriate Abx Use for Tx of Nonspecific URTI in Adults Recommendation 3. Purulent secretions from the nares or throat (commonly observed in patients with uncomplicated upper respiratory tract infection) predict neither bacterial infection nor benefit from antibiotic treatment [A].(unless it persists for > 10 to 14 days ?)

14 Appropriate Abx Use for Tx of Nonspecific URTI in Pediatrics Controlled trials of antimicrobial treatment failed to change the course or outcome No evidence of a protective effect for antimicrobial treatment to prevent LRTIs (Gadomski AM et al PIDJ 1993;12:115-20) Chemoprophylaxis can help prevent AOM in some high-risk child (Rosenstein N et al Pediatrics 1998;101:181-4)

15 Appropriate Abx Use for Tx of Acute Rhinosinusitis in Adults Most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral URTI [A]. Sinus radiography is not recommended for diagnosis in routine cases [B].

16 Appropriate Abx Use for Tx of Acute Rhinosinusitis in Adults Bacterial and viral rhinosinusitis are difficult to differentiate on clinical grounds [B].  Acute Bacterial Sinusitis: Symptoms lasting 7 days or more, unilateral maxillary pain, maxillary toothache, unilateral tenderness of the maxillary sinus mucopurulent nasal discharge  Gold standard: Sinus aspiration, grow at least 10 5 organisms/ml

17 Appropriate Abx Use for Tx of Acute Rhinosinusitis in Adults  Sinusitis in radiography complete opacification and air-fluid level  Sensitivity: 80% (71-87%), specificity: 85%(76-91%) various degrees of mucosa thickening  Specificity: 40~50%  Absence of all three findings  Sensitivity: ~90%

18 Appropriate Abx Use for Tx of Acute Rhinosinusitis in Adults Who should not be treated: Acute bacterial sinusitis (mild or moderate) Who should be treated: severe or persistent (more than 7 days) moderate symptoms + specific findings of bacterial sinusitis

19 Appropriate Abx Use for Tx of Acute Rhinosinusitis in Adults For initial treatment,the most narrow- spectrum agent active against the likely pathogens,Streptococcus pneumoniae and Haemophilus influenza should be used High dose Amoxicillin (most favored) Augmentin, Fluroquinolones, Telithromycin X Erythromycin

20 Appropriate Abx Use for Tx of Acute Pharyngitis in Adults An inflammatory illness of mucous membranes and underlying structures of throat Frequently involve nasopharynx, uvula, soft palate Erythema, exudate, ulceration Usually acute, sore throat Common causes of pharyngotonsillitis Group A beta-hemolytic streptococci,Epstein-Barr virus,Adenovirus,Influenza viruses, Enteroviruses, Parainfluenza viruses

21 Appropriate Abx Use for Tx of Acute Pharyngitis in Adults

22 The large majority of adults with acute pharyngitis have a self-limited illness, for which supportive care only is needed. Antibiotic treatment of adult pharyngitis benefits only those patients with GABHS infection. Complications: Acute Rheumatic Fever, Acute Glomerulonephitis, Peritonsillar abscess, Disease contagion

23 Diagnosis of Strep. pharyngitis Throat culture Rapid antigen test Centor criteria : history of fever, tonsillar exudates, no cough, and tender anterior cervical lymphadenopathy (lymphadenitis) Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosisof strep throat in adults in the emergency room. Med Decis Making.1981;1:239-46.

24 Throat cultures Does not always correlate with antistreptolysin titers Produces results that vary depending on technique Throat cultures also fail to distinguish acute infection from the carrier state.  Not recommended for the routine primary evaluation of adults with pharyngitis or for confirmation of negative results on rapid antigen tests

25 Indications of Throat Cultures Investigations of outbreaks of GABHS disease Monitoring the development and spread of antibiotic resistance When such pathogens as gonococcus are being considered.

26 Rapid Antigen Tests Approximately the same sensitivity and greater specificity for predicting results of throat culture “Medicalize” pharyngitis because patients would need to see a physician for the test to be performed.

27 Appropriate Abx Use for Tx of Acute Pharyngitis in Adults Principle 1. Clinically screen all adult patients with pharyngitis for the presence of the four Centor criteria Principle 2. Do not test or treat patients with none or only one of these criteria. These patients are unlikely to have GABHS infections [A].

28 Appropriate Abx Use for Tx of Acute Pharyngitis in Adults Principle 3. For patients with two or more criteria, the following strategies are appropriate: a) Test these patients by using a rapid antigen test, and limit Abx to patients with positive results b) Abx for patients with four criteria, and patients with 2~3 criteria plus rapid test (+) c) Limit Abx to those with 3~4 criteria only Principle 4. Administer appropriate analgesics, antipyretics, and supportive care to all patients with pharyngitis [A].

29 Appropriate Abx Use for Tx of Acute Pharyngitis in Adults Drug of Choice: Single dose of intramuscular penicillin ( 1.2 MU for adults) Penicillin VK 500mg orally 2~3 times per day for 10 days Alternative: 1 o generation cephalosporins, macrolides, clindamycin Neither repeat bacterial test of patients or testing of asymptomatic household contacts recommended A small percentage have a recurrence Bisno AL et al Clin Infect Dis 2002;35:113-25)

30 The above guildlines do not apply to: Patients of rheumatic fever, valvular heart disease, immunosuppression, recurrent or chronic pharyngitis (symptoms≥7days), or to patients whose sore throats have a cause other than acute infectious pharyngitis. A known epidemic of acute rheumatic fever or streptococcal pharyngitis or in nonindustrialized countries in which the endemic rate of acute rheumatic fever is much higher

31 Appropriate Abx Use for Tx of Acute bronchitis in Adults The evaluation of adults with an acute cough illness (< 3 weeks) should focus on ruling out serious illness, particularly pneumonia. Pneumonia: abnormalities in vital signs (HR≥ 100 beats/min, RR≥ 24 breaths/min, or temp ≥ 38 °C), CXR(eg. Focal consolidation), rales, egophony, and fremitus

32 Appropriate Abx Use for Tx of Acute bronchitis in Adults Technically definition: inflammation of bronchial respiratory mucosa, resulting in productive cough Clinical definition : not well established, usually cough with or without fever or sputum production Lack of a standardized case definition (O’brien KL et al Pediatrics 1998;101:178-81)

33 Pathogens of Acute bronchitis Viral pathogens account for the majority of agents Parainfluenza viruses, RSV, influenza viruses 20% adults with rhinovirus colds continue to cough > 14 days (Gwaltney JM et al JAMA 1967;202:494-500) Mycoplasma pneumoniae, Chlamydia pneumoniae, recognized pathogens in children >5y/o Neither production of sputum nor character of sputum predictive of a bacterial etiology for cough Nasopharyngeal culture poor predictors of true bacterial pathogens Fever not indicate cough related to a bacterial infection (O’brien KL et al Pediatrics 1998;101:178-81)

34 Pathogens of Acute bronchitis The majority of prolonged cough illness are allergic, postinfectious, or viral in nature Reactive airway disease one of the most common causes, respond to bronchodilators Pertussis, particularly among older children and adults Mycoplasma Pneumoniae, in school children No specific or pathognomonic signs of cough A macrolide small effect on shortening the duration of cough (O’brien KL et al Pediatrics 1998;101:178-81)

35 Appropriate Abx Use for Tx of Acute bronchitis in Adults Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough. Antimicrobial treatment for prolonged cough (>10 days) may be indicated occasionally Pertussis Mycoplasma pneumoniae, usually in children > 5 y/o, a macrolide agent Underlying chronic pulmonary disease with acute exacerbation

36 Diagnosis of Acute Otitis Media in Children Pediatrics. 113(5):1451-65, 2004 May. A history of acute onset, Identify signs of middle-ear effusion (MEE), Evaluate for the presence of signs and symptoms of middle-ear inflammation.

37 Managements of AOM in Children Pediatrics. 113(5):1451-65, 2004 May Assessment of “pain”: If pain is present, the clinician should recommend treatment to reduce pain. (strong recommendation) Observation in a child with uncomplicated AOM is an option for selected children

38 Managements of AOM in Children Pediatrics. 113(5):1451-65, 2004 May Observation is an appropriate option only when follow-up can be ensured and antibacterial agents started if symptoms persist or worsen. Nonsevere illness is mild otalgia and fever

39 Managements of AOM in Children Pediatrics. 113(5):1451-65, 2004 May If a decision is made to treat with an antibacterial agent, the clinician should prescribe amoxicillin 80 to 90 mg/kg/day for most children Treatment course:  10 days : younger children, children with severe disease  5~7 days :children 6 years of age and older with mild to moderate disease If the patient fails to respond to the initial management within 48 to 72 hours  Reassessment

40 Recommended Antibacterial Agents Pediatrics. 113(5):1451-65, 2004 May

41 Managements of AOM in Children Pediatrics. 113(5):1451-65, 2004 May Clinicians should encourage the prevention of AOM through reduction of risk factors (strong recommandation) Ex: genetic predisposition, premature birth, male gender, presence of siblings in the household, and low socioeconomic status, supine bottle- feeding (“bottle propping”), pacifier use in the second 6 months of life, exposure to passive tobacco smoke

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