1. Outpatient Management of CAP, Sinusitis, AECB and Pharyngitis David A. Pegues, MD Division of Infectious Diseases David Geffen School of Medicine at UCLA

2. Etiologic Agents in Community-acquired Respiratory Tract Infections Zeckel ML, et al. Clin Ther . 1992;14(2):214-229. Hoberman A, et al. Pediatr Infect Dis J. 1996;15(10)955-962. Bartlett JG, et al. N Engl J Med . 1995;333(24):1618-1624. * Also Mycoplasma pneumoniae , Chlamydia pneumoniae , Legionella pneumophila , and rarely Staphylococcus aureus . 10% - 15% 8% - 12% 23% - 25% 2% - 8% 20% - 25% 20% - 25% 30% - 35% 15% - 25% 30% - 35% 25% - 30% 7% - 10% 35% - 55% Acute otitis media Acute maxillary sinusitis AECB CAP* Moraxella catarrhalis Haemophilus influenzae Streptococcus pneumoniae Disease

5. Age-Specific Rates of Hospital Admission for CAP, by Pathogen 120 100 80 60 40 20 0 18 – 34 35 – 49 50 – 64 65 – 79 = 80 Age Group, Years Cases per 100,000 Population Chlamydia pneumoniae * Legionella spp * Mycoplasma pneumoniae * Streptococcus pneumoniae † Chlamydia pneumoniae * Legionella spp * Mycoplasma pneumoniae * Streptococcus pneumoniae † , , Marston BJ, et al. Arch Intern Med 1997:157:1709-18.

6. 37 y.o. father with 2 children in daycare, cough, fever, and altered mental status

9. A healthy 30 y.o. female with insidious onset of fever, malaise, HA and non-productive cough

12. Initial Empiric Therapy for CAP in Adult Outpatients, IDSA 2003 Mandell LA, et al. Clin Infect Dis 2003;37:1405-33.

15. Factors Improving Outcome in CAP Decreased LOS 6 Early mobilization Decreased LOS 4 No difference in LOS, decreased cost and mortality* ,5 Critical pathway Decreased LOS/cost 3 Decreased 30 - day mortality 2 Appropriate antimicrobials Decreased 30 - day mortality* ,1 Blood cultures within 24 hr Decreased 30 - day mortality* ,1,2 Early antimicrobials Outcome Factors Decreased LOS 6 Early mobilization Decreased LOS 4 No difference in LOS, decreased cost and mortality* ,5 Critical pathway Decreased LOS/cost 3 Early IV to PO switch Decreased 30 - 2 Appropriate antimicrobials Decreased 30 - day mortality* ,1 Blood cultures within 24 hr Decreased 30 - day mortality* ,1,2 Outcome Factors 1. Meehan TP et al. JAMA . 1997;278:2080 – 2084. 2. Gleason PP et al. Arch Intern Med . 1999;159:2562 – 2572. 3. Ramirez JA et al. Arch Intern Med . 1999;159:2449 – 2454. 4. Marrie TJ et al. JAMA . 2000;283:749 – 755. 5. Dean NC et al. Am J Med. 2001;110:451 – 457. 6. Mundy LM et al. Chest . 2003;124:883 – 889. LOS=length of stay. *Retrospective studies with patients at least aged 65 years. LOS=length of stay. *Retrospective studies with patients at least aged 65 years.

17. Recommendations for the Use of 23-Valent Pneumococcal Vaccine MMWR 1997; 46 (RR8).

18. Efficacy of Pneumococcal Polysaccharide Vaccine in Patients at Moderate to High Risk of Serious Disease

19. Effect of Empiric Therapy with Macrolides on Length of Stay in Patients Hospitalized with CAP Stahl JE, et al. Arch Intern Med. 1999;159:2576-80.

21. In Vitro* MIC 90 Activity Against Lower Respiratory Pathogens Felmingham et al. J Antimicrob Chemother. 2002 Sep;50 Suppl S1:25-37. Hoban & Felmingham. J Antimicrob Chemother. 2002 Sep;50 Suppl S1:49-59. Fung-Tomc JC, et al. J Antimicrob Chemother. 2000 Apr;45(4):437-46 2 0.25 16 <0.25 0.12 0.03 0.06 M. catarrhalis (ß-lac+ ) 0.5 <0.12 <0.12 <0.25 0.12 0.03 0.06 M. catarrhalis (ß-lac-) 2 2 >16 16 0.03 0.015 0.03 H. influenzae (ß-lac+) 2 1 1 8 0.03 0.015 0.03 H. influenzae (ß-lac-) 8 2 2 8 0.5 1 0.25 S. pneumoniae Cefur mg/L Amox/Clav mg/L Amox mg/L Clari mg/L Gati mg/L Levo mg/L Moxi mg/L

24. Pathophysiology—Rhinosinusitis Adapted from: Kennedy DW, ed. Sinus Disease: Guide to First-Line Management. Darien CT, Health Communications, 1994. Secretions thicken; pH changes. Ostium is closed. Mucosal gas metabolism changes. Cilia and epithelium are damaged. Change in host milieu creates culture medium for bacterial growth in closed cavity. Retained secretions cause tissue inflammation. Bacterial infection develops in the sinus cavity. Mucosal thickening creates further blockage. Secretions stagnate. Mucosal congestion or anatomic obstruction blocks airflow and drainage.

25. Signs and Symptoms Associated with the Diagnosis of Sinusitis * Facial pain or pressure alone does not constitute a suggestive history in the absence of other findingsin the Major category. Osguthorpe JD. Am Fam Physician . 2001;63:69-76. Major Facial pain/pressure/fullness* Nasal obstruction/blockage Nasal discharge/purulence Hyposmia/anosmia Fever (acute phase) Minor Headaches Halitosis Fatigue Dental pain Cough Ear pain/pressure/fullness

26. Plain Radiograph and CT Scans of the Paranasal Sinuses Piccirillo, J. F. N Engl J Med 2004;351:902-910

27. Various Signs and Symptoms Used to Predict the Presence of Sinusitis Piccirillo, J. F. N Engl J Med 2004;351:902-910

29. AAOHNS Rhinosinusitis Guidelines Anon JB et al. Otolaryngol Head Neck Surg. 2004;130(suppl 1):1-45. Moxi/gati/levo Rifampin+clindamycin Moxi/gati/levo Amox/clav Ceftriaxone Combination therapy Reevaluate patient Mild disease with no recent antimicrobial use (past 4-6 weeks) TMP/SMX Doxycycline Azithro, clarithro, erythro Amox/clav Amox Cefpodoxime Cefuroxime Cefdinir Mild disease with recent antimicrobial use (past 4-6 weeks) or moderate disease Severity Reevaluate patient Moxi/gati/levo Amox/clav Ceftriaxone Moxi/gati/levo Clindamycin and rifampin β -Lactam Allergic No Yes No Initial Therapy Switch Therapy Options Reevaluate patient Yes

33. A 15-year-old boy with sinusitis causing right proptosis, telecanthus, and malar flattening

37. Infection and Inflammation of Acute Bacterial Exacerbations of Chronic Bronchitis Initiating Factors (e.g., Smoking, Childhood Respiratory Disease) Bacterial Products (LOS) Alteration of Elastase – Anti-Elastase Balance Increased Elastolytic Activity in Lung Progression of COPD Impaired Mucociliary Clearance Inflammatory Response (Cytokines, Enzymes, etc.) LOS = lipooligosaccharide Murphy et al, 1992. Bacterial Colonization Damage to Airway Epithelium

40. MOSAIC Study: Clinical Cure of ABECB at 7-10 Days Posttherapy Moxifloxacin Comparator ITT PP (95% CI; 1.40, 14.87) (95% CI; 0.26, 15.95) 71% 63% 70% 62% Wilson R et al. Chest. 2004;125:953-964. Moxifloxacin 400 mg QD for 5 days vs. Amox 500 gm tid for 7 days, clarithromycin 500mg bid for 7 days, or cefuroxime 250 mg bid for 7 days Clinical Cure (%) 191/274 185/298 P < .02 251/354 236/376

44. Diagnostic and Treatment Algorithm of Acute Pharyngitis GABHS = Group A  -hemolytic streptococci. Bisno et al. Clin Infect Dis . 1997;25:574-583. Clinical and epidemiologic features Not suggestive of GABHS Symptomatic therapy Antimicrobial therapy Possible GABHS Throat culture Rapid antigen detection test – – + +