An Evidence-Based Treatment of Upper Respiratory Tract Infections

Transcription

1 An Evidence-Based Treatment of Upper Respiratory Tract Infections Ralph Gonzales, MD, MSPH Professor of Medicine; Epidemiology & Biostatistics University of California, San Francisco May 25, 2008

2 Outline Acute cough illness Bronchitis; pertussis; influenza Sinusitis Pharyngitis Special Topics How to say no to antibiotics Therapeutic windows

3 General Approach Making the Diagnosis Excluding Serious Illness Do I need a Diagnostic Test? Determining Treatment Symptomatic Therapy Antimicrobial Therapy Communicating Prognosis When to Return for Evaluation

4 Management Principles for Uncomplicated Acute Bronchitis

5 Bronchitis -CDC; ACP; AAFP; IDSA 2001 The evaluation of adults with acute cough illness should focus on ruling out serious illness, particularly pneumonia In healthy, nonelderly adults, pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds, and CXR is usually not indicated. When cough>3 weeks, CXR may be warranted in absence of other known causes. Gonzales et al, 2001

6 Pneumonia Probabilities Cough, Fever, Tachycardia and Crackles 20 Cough + Nl Vital Signs 0 Dullness to Percussion Crackles Fever Tachycardia PreTest Prob Probability of Pneumonia Metlay et al. JAMA. 1997;278:

7 Acute Bronchitis -Therapeutic Objectives Symptoms Pathophysiology Treatment Cough -bronchial RAD -bronchodilators -mucus production -decongestants -post-nasal drip -sinus therapy -acid reflux -H2B; PPI -cough suppressants Wheezing/SOB -bronchial RAD -bronchodilators

8 Resolution of Acute Bronchitis % Patients Stott, BMJ 1976 No Antibiotic (+) Antibiotic Days with cough

9 Uncomplicated Acute Bronchitis -azithromycin vs. vitamin C (Lancet 2002;359; ) Return to Usual Activities

10 Acute Bronchitis: -bronchial hyperresponsiveness Airflow obstruction in acute bronchitis without underlying lung disease <=80 >80 FEV1, % predicted Eur Resp J 1994;7:1239

11 Acute cough illness treatment -bronchodilator treatment Randomized, placebo controlled trials Melbye bronchitis 73 fenoterol aerosol Decrease symptoms 1991 Improved FEV1 Hueston bronchitis 34 oral albuterol vs. Decrease 1 week 1991 erythromycin (41% vs. 82%) Hueston bronchitis 46 albuterol aerosol vs. Decrease 1 week 1994 (placebo + erythro) (61% vs. 91%) Littenberg nonspecific 104 albuterol aerosol No benefit 1996 cough

12 OTC Cough Therapies -Cochrane Review, 2004 Antitussives codeine: 2 trials; no differences dextromethorphan: 2 of 3 trials show benefit Expectorants (guaifenesin): 1 of 2 trials benefit Mucolytics: 1 trial inconsistent benefit Antihistamine-Decongestant Combinations 1 of 2 trials show benefit Dextro-salbutamol: reduced nocturnal cough only

13 Acute cough illness: evaluation summary Acute Cough Illness with or w/o phlegm Patient Characteristics Vital Sign Abnormalities Elderly Immunosuppression COPD or CHF HR > 100 bpm RR > 24 br/min, or T > 38 o C Yes Is Influenza Likely? Yes No PEx Findings Consolidation, or Pleural Effusion No Yes Consider CXR No Negative Treatment Options* Positive Treat Pneumonia

14 When to consider zebras Cough > 3 weeks and normal CXR Meds, asthma, GERD, postnasal drip, pertussis Nocturnal Cough GERD/postnasal drip, cough-variant asthma, CHF

15 Pertussis not just for children anymore

16 Pertussis not just for children anymore DPT-related immunity wanes as early as 3 years and absent after years attack rates as high as 100% 10-15% adults seeking care for persistent cough (>3 wks) have evidence of pertussis No clinical features distinguish pertussis in previously immunized adults

17 Pertussis Diagnosis Dacron nasopharyngeal swab or nasal saline wash PCR is now standard much better sensitivity than culture or DFA; but still false-negatives and periodic false-positives c/w serology. No FDA-licensed tests yet Coordinate with public health dept Treatment Macrolides; trimethoprim-sulfa if macrolide-allergy Probably won t help cough duration if started after 10 days of illness, which can last 3-6 months Reasonable to provide empirical Abx treatment to contacts with cough, and close contacts/household members as prophylaxis.

18 The CDC now recommends pertussis booster for all of the following groups, except 1. Adolescents 2. Elderly (>65 years) 3. Post-partum women 4. Physicians and nurses 5. Physician office staff

19 PREVENTION: Pertussis Boosters -ACIP 2007 Recs (MMWR 2006;55:RR-17) Routine Single Tdap instead of dt at age Tdap (instead of dt) in adults if > 10 years since dt Tdap when dt within 2-10 years Adult contacts of infants < 12 months Women prior to pregnancy; else post-partum Healthcare workers (all staff) Rare Adverse Events Arthus Reaction Extensive Limb Swelling

20 In a 35 yo woman with purulent nasal discharge for 10 days, which additional symptom would warrant antibiotic therapy? 1. Ear pain 2. Sore throat 3. Cough 4. Tooth ache 5. Hoarse voice

21 Rhinosinusitis: Diagnosis (1) The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for [B] (1) rhinosinusitis symptoms > 7 days + (2) purulent nasal secretions + (3) maxillary pain/tenderness in face/teeth

22 Rhinosinusitis: Diagnosis (2) rarely some patients with acute bacterial rhinosinusitis present with dramatic symptoms of severe unilateral maxillary pain, swelling and fever

23 Bacterial Sinusitis? Tough Call Cx (+) sinus aspirate purulent sinus aspirate CT scan (a) Xray (b) high clinical suspicion sinus symptoms Bacterial Sinusitis, % (a) CT scan criteria of air-fluid level or complete opacification. (b) Xray criteria of mucosal thickening, air-fluid level or complete opacification.

24 Rhinosinusitis: Rx Studies Author Patient Selection Treatment Arms Antibiotic Rx* Placebo Rx* Lindbaek, 1996 clinical suspicion + CT Scan Dx amoxicillin; penicillin V; placebo D10 86% 57% van Buchem 1997 clinical suspicion + Xray Dx amoxicillin; placebo D14 83% 77% Stalman, 1997 clinical criteria doxycycline; placebo D10 85% 85% Bucher, 2003 clinical criteria (only 32% Sx > 7 days) amox-clavulanate; placebo D14 75% 75% Merenstein, 2005 clinical criteria (100% Sx > 7 days) amoxicillin; placebo D14 48% 37% *Percent improved or cured

25 Williamson, JAMA Abx +/- nasal steroids RCT Abx + steroid Abx + placebo steroid + placebo placebo + placebo No. of Sx days (n = 51) (n = 60) (n=63) (n=61) median (IQR) 7 (4-14) 7 (4-10) 7 (4-14) 7 (5-14)

26 Rhinosinusitis: Diagnosis (1) The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for [B] (1) rhinosinusitis symptoms > 7 days + (2) purulent nasal secretions + (3) maxillary pain/tenderness in face/teeth

27 Young et al. Lancet Meta-Analysis, Meta-analysis of clinical criteria-based RCTs of antibiotics for acute sinusitis UNIQUE: aggregated patient-level data; therefore able to examine specific signs/sx Results: Duration of illness or severity of symptoms did not predict antibiotic benefit Purulent nasal discharge marginally significant

28 Odds Ratio for Cure with Antibiotic Rx for Acute Sinusitis Young J et al, Lancet 2008

29 Rhinosinusitis: Diagnosis (1) The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for [B] (1) rhinosinusitis symptoms > 7 days + (2) purulent nasal secretions + (3) maxillary pain/tenderness in face/teeth

30 Rhinosinusitis: Abx Rx Acute rhinosinusitis resolves without antibiotic treatment in most cases [A] Antibiotic treatment should be reserved for patients with moderately severe symptoms who meet criteria for clinical diagnosis of acute bacterial rhinosinusitis and for those with severe symptoms regardless of duration of illness.

31 Acute Sinusitis -Therapeutic Objectives Symptoms Pathophysiology Treatment Pain -increased sinus pressure due - sinus drainage inflammation & obstruction -nasal saline wash -nasal decongestant -if >7-10 days of Sx -NSAIDs - bacterial infection risk -Antibiotics Congestion -increased mucus production -oral decongestants -infection; recurrent; allergic -nasal steroids

32 In a 25 yo man with severe sore throat, which clinical feature decreases his likelihood of have strep throat? 1. History of fever 2. Tonsillar exudate 3. Cough 4. Anterior cervical lymphadenopathy 5. Hoarse voice

33 Pharyngitis: Diagnosis Clinically screen all adult patients with pharyngitis for the presence of 4 criteria: history of fever tonsillar exudates tender anterior cervical LAN absence of cough Do not test or treat patients with none or only 1 of these criteria

34 Spectrum Bias in GAS Test Sensitivity of RAT Pediatrics Adults Centor Score * * * * 97 *groups combined in study Peds Ref: Hall MC et al. Pediatrics 2004;114:182 Adult Ref: Dimatteo LA et al. Ann Emerg Med 2001;38:648

35 Pharyngitis: Abx Rx Test patients with 2-4 criteria using a rapid antigen test, and limit Abx to patients with positive test results [D], OR Test patients with 2 or 3 criteria, and limit Abx to patients with positive test results or patients with 4 criteria [D], OR Do not use any diagnostic tests, and limit Abx to patients with 3 or 4 criteria [B]

36 GAS Rapid negative, but patient Sx worsen possibilities? False-negative rapid GAS test Infectious mononucleosis Non-group A streptococcal infection Group C, Group D Gonorrhea Acute HIV Peritonsillar abscess Lemierre s syndrome (septic thrombophlebitis)

37 Streptococcal Pharyngitis -Therapeutic Objectives Symptoms Pathophysiology Treatment sore throat -inflammation -NSAIDs -infection -antibiotics

38 How to help patients say no to antibiotics for viral ARIs Illness labeling: use chest cold, not bronchitis Validate illness severity; focus on symptom relief Provide a contingency plan Discuss downside of unnecessary antibiotic use risk of carriage/spread of antibiotic-resistant bacteria Patient-physician communication Explain the illness Spend enough time Treat with respect

39 Therapeutic Windows in ARI Treatments Influenza Sx 2 days GAS pharyngitis Sx To prevent ARF 2 days 10 days Pertussis cough 7-10 days

40 Gracias

41 CDC/ACP/AAFP/IDSA -Antibiotic Principles for ARIs Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JH, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults: Background, Specific Aims and Methods. Ann Intern Med 2001;134: Cooper RJ, Hoffman JR, Bartlett JG, Besser RE, Gonzales R, Hickner JH, Sande MA. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med 2001;134: Hickner JH, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med 2001;134: Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JH, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann Intern Med 2001;134:

42 Bronchitis References Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough and purulent sputum. BMJ. 1976;2(6035): Melbye H, et al. Reversible airflow limitation in adults with respiratory infection. Eur Respir J. 1994;7: Gonzales R et al. Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. JAMA. 1999;281: Evans AT, et al. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Lancet. 2002;359(9318): ). Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004(4):CD Nennig ME, et al. Prevalence and incidence of adult pertussis in an urban population. JAMA 1996;275: Metlay JP, Fine MJ. Testing strategies in the initial management of patients with community-acquired pneumonia. Ann Intern Med. 2003;138: Preventing Tetanus, Diphtheria, and Pertussis Among Adults: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55:RR-17. Pawar S, et al. Treatment of postnasal drip with proton pump inhibitors: a prospective, randomized, placebo-controlled study. Am J Rhinol 2007;21:

43 Acute Rhinosinusitis Refs Lindbaek M, et al. Randomized, double blind, placebo controlled trial of penicillin V and amoxycillin in treatment of acute sinus infections in adults. BMJ 1996;313(7053): Stalman W, et al. The end of antibiotic treatment in adults with acute sinusitislike complaints in general practice? A placebo-controlled double-blind randomized doxycycline trial. Br J Gen Pract 1997;47(425): van Buchem FL, et al. Primary-care-based randomized placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis. Lancet 1997;349(9053): Bucher HC, et al. Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind, randomized trial in general practice. Arch Intern Med. 2003;163: Merenstein D, et al. Are antibiotics beneficial for patients with sinusitis complaints? A randomized double-blind clinical trial. J Fam Pract 2005;54: Williamson et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis: a randomized controlled trial. JAMA 2007;298: Young et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. Lancet 2008; 371(9616):874-6

44 Acute Pharyngitis Refs Centor RM, Witherspoon JM, Dalton HP, et al. The diagnosis of strep throat in adults in the emergency room. Med Decis Making 1981; 1: Zwart S, Sachs APE, Ruijs GJHM, et al. Penicillin for acute sore throat: randomised double blind trial of seven days versus three days treatment or placebo in adults. BMJ 2000; 320: DiMatteo L, Lowenstein SR, Brimhall B, et al. The relationship between the clinical features of pharyngitis and the sensitivity of a rapid antigen test: evidence of spectrum bias. Ann Emerg Med. 2001;38: Bulloch B, Kabani A, Tenenbein M. Oral dexamethasone for the treatment of pain in children with acute pharyngitis: a randomized, double-blind, placebocontrolled trial. Ann Emerg Med. 2003;41: Kiderman A, Yaphe J, Bregman J, Zemel T, Furst AL. Adjuvant prednisone therapy in pharyngitis: a randomised controlled trial from general practice. Br J Gen Pract 2005;55:218. Shah M, et al. Severe acute pharyngitis caused by group C streptococcus. J Gen Intern Med 2007;22: Centor RM, et al. Pharyngitis management: defining the controversy. J Gen Intern Med 2007;22: