Cap Sinusitis Pharyngitis Im0306.Ppt


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  • Cap Sinusitis Pharyngitis Im0306.Ppt

    1. 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. 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
    3. 3. CAP Statistics--United States <ul><li>Influenza and pneumonia--leading infectious cause of death: </li></ul><ul><ul><li>5 th leading cause of death in persons aged > 65 y </li></ul></ul><ul><li>5.6 million cases of CAP per year: </li></ul><ul><ul><li>1.1 million cases hospitalized </li></ul></ul><ul><ul><li>average LOS 2 days longer for those aged > 65 y vs. <65 y </li></ul></ul><ul><li>Mortality: </li></ul><ul><ul><li>overall--1-5%; hospitalized cases--25% </li></ul></ul><ul><li>Cost: </li></ul><ul><ul><li>$14 billion/y in healthcare costs and $9 billion/y in lost wages </li></ul></ul>
    4. 4. CAP Probabilities in Ambulatory Care <ul><li>Baseline CAP prevalence 5% </li></ul><ul><li>Scenario 1: </li></ul><ul><ul><li>patient with cough only </li></ul></ul><ul><ul><li>1%-13% probability of CAP </li></ul></ul><ul><li>Scenario 2: </li></ul><ul><ul><li>cough, fever, tachycardia, crackles </li></ul></ul><ul><ul><li>18%-42% probability of CAP </li></ul></ul><ul><li>Scenario 3: </li></ul><ul><ul><li>CAP prevalence 10% </li></ul></ul><ul><ul><li>32%-60% probability of CAP if all 4 signs present </li></ul></ul>Metlay JP, Fine MJ. Ann Intern Med 2003;138:109-18 .
    5. 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. 6. 37 y.o. father with 2 children in daycare, cough, fever, and altered mental status
    7. 7. Modifying Factors that Increase the Risk of Infection with Specific Pathogens <ul><li>Drug-resistant pneumococci: </li></ul><ul><ul><li>age > 65 yr </li></ul></ul><ul><ul><li> -Lactam therapy w/in 3 mo </li></ul></ul><ul><ul><li>alcoholism </li></ul></ul><ul><ul><li>immune-suppressive illness </li></ul></ul><ul><ul><li>multiple medical comorbidities </li></ul></ul><ul><ul><li>exposure to a child in day care </li></ul></ul><ul><li>Enteric gram-negatives </li></ul><ul><ul><li>residence in a nursing home </li></ul></ul><ul><ul><li>cardiopulmonary disease </li></ul></ul><ul><ul><li>multiple medical comorbidities </li></ul></ul><ul><ul><li>recent antibiotic therapy </li></ul></ul><ul><li>Pseudomonas aeruginosa </li></ul><ul><ul><li>structural lung disease </li></ul></ul><ul><ul><li>> 10 mg of prednisone/day </li></ul></ul><ul><ul><li>broad spectrum abx. for >7 d in the past month </li></ul></ul><ul><ul><li>malnutrition </li></ul></ul>Amer Rev Resp Dis 2001;163:1730-54.
    8. 8. Impact of Penicillin Susceptibility on Medical Outcomes for Adult Patients with Bacteremic Pneumococcal Pneumonia <ul><li>Retrospective cohort study conducted in the greater Atlanta region during 1994 </li></ul><ul><li>192 adult patients with bacteremic pneumococcal pneumonia </li></ul><ul><li>Pen-NS Pen-S RR </li></ul><ul><ul><ul><li>(n=44) (n=148) (95% CI) </li></ul></ul></ul><ul><li>PSI risk class IV or V 20 (46) 46 (31) P=0.05 </li></ul><ul><li>Death from pneumonia 10 (23) 16 (11) 2.1 (1-4.3) </li></ul><ul><li>Suppurative complications 4 (9) 3 (2) 4.5 (1-19.3) </li></ul>Metaly JP, et al. Clin Infect Dis 2000;30:520-28
    9. 9. A healthy 30 y.o. female with insidious onset of fever, malaise, HA and non-productive cough
    10. 10. Group 1: Outpatients, No Cardiopulmonary Disease, No Modifying Factors <ul><li>Organism </li></ul><ul><li>Streptococcus pneumonia </li></ul><ul><li>Mycoplasma pneumoniae </li></ul><ul><li>Chlamydia pneumoniae </li></ul><ul><li>Hemophilus influenzae </li></ul><ul><li>Respiratory viruses </li></ul><ul><li>Legionella spp. </li></ul><ul><li>Mycobacterium tuberculosis </li></ul><ul><li>Endemic fungi </li></ul><ul><li>Therapy </li></ul><ul><li>azithromycin or clarithromycin </li></ul><ul><li>or </li></ul><ul><li>doxycycline </li></ul>Amer Rev Resp Dis 2001;163:1730-54.
    11. 11. Group 2: Outpatients, with Cardiopulmonary Disease, and/or Modifying Factors <ul><li>Organism </li></ul><ul><li>S. pneumoniae (incl. DRSP) </li></ul><ul><li>M. pneumonia, C. pneumoniae </li></ul><ul><li>Mixed infection </li></ul><ul><li>H. influenzae </li></ul><ul><li>Enteric gram negatives </li></ul><ul><li>Respiratory viruses </li></ul><ul><li>M. catarrhalis </li></ul><ul><li>Legionella spp. </li></ul><ul><li>Aspiration (anaerobes) </li></ul><ul><li>M. tuberculosis </li></ul><ul><li>Endemic fungi </li></ul><ul><li>Therapy </li></ul><ul><li> -lactam </li></ul><ul><ul><li>cefpodoxime </li></ul></ul><ul><ul><li>cefuroxime </li></ul></ul><ul><ul><li>high-dose amoxicillin </li></ul></ul><ul><ul><li>amoxicillin/clavulanate </li></ul></ul><ul><ul><li>ceftriaxone then cefpodoxime </li></ul></ul><ul><li>plus </li></ul><ul><li>macrolide or doxycycline </li></ul><ul><li>or </li></ul><ul><li>antipneumococcal FQ alone </li></ul>Amer Rev Resp Dis 2001;163:1730-54.
    12. 12. Initial Empiric Therapy for CAP in Adult Outpatients, IDSA 2003 Mandell LA, et al. Clin Infect Dis 2003;37:1405-33.
    13. 13. Pneumonia Severity Index <ul><li>Risk classes I and II: </li></ul><ul><ul><li>low risk of death </li></ul></ul><ul><ul><li>treat as outpatients </li></ul></ul><ul><li>Elderly or risk class III: </li></ul><ul><ul><li>consider short hospitalization (1 day) </li></ul></ul><ul><li>Risk class IV and V </li></ul><ul><ul><li>hospitalize </li></ul></ul><ul><li>Inpatient treatment: </li></ul><ul><ul><li>O2 saturation <90 </li></ul></ul><ul><ul><li>hemodynamic instability </li></ul></ul><ul><ul><li>co-morbid conditions </li></ul></ul><ul><ul><li>inability to take PO meds </li></ul></ul>Halm EA, Teirstein AS. NEJM 2002:347:2039-45.
    14. 14. Risk Assessment: CURB-65 Score 0 – 1: Low risk. Suitable for outpatient treatment. Score 2: Intermediate risk. Consider hospitalization. Score = 3: High risk. Urgent hospitalization. Lim WS et al. Thorax . 2003;58:377 – 382. <ul><li>Confusion* </li></ul><ul><li>Urea >7 </li></ul>mmol /L <ul><li>Respiration </li></ul>> 30/min <ul><li>Systolic BP < 90 mmHg or </li></ul>diastolic BP < 60 mm Hg <ul><li>Age > 65 years </li></ul>Mortality predictors - Mortality, % CURB - 65 SCORE 0 – 1 2 = 3 Risk groups *Mental Test Score of < 8 or new disorientation in person, place, or time. 1.5 9.2 22 0 5 10 15 20 25
    15. 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.
    16. 16. Timing of Antibiotic Administration and Outcomes for Medicare Patients Hospitalized With CAP <ul><li>Retrospective study of a national random sample of 18,209 Medicare patients: </li></ul><ul><ul><li>>65 years hospitalized with CAP from 7/98-3/99 </li></ul></ul><ul><ul><li>75.6% did not receive outpatient antibiotics </li></ul></ul><ul><li>Antibiotic within 4 hours of arrival at the hospital: </li></ul><ul><ul><li> in-hospital mortality (6.8% vs 7.4%; AOR, 0.85), </li></ul></ul><ul><ul><li> 30 d mortality (11.6% vs 12.7%; AOR, 0.85) </li></ul></ul><ul><ul><li> LOS exceeding 5-day median (42.1% vs 45.1%; AOR, 0.90) </li></ul></ul>Houck, PM, et al. Arch Intern Med. 2004;164:637-44.
    17. 17. Recommendations for the Use of 23-Valent Pneumococcal Vaccine MMWR 1997; 46 (RR8).
    18. 18. Efficacy of Pneumococcal Polysaccharide Vaccine in Patients at Moderate to High Risk of Serious Disease
    19. 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.
    20. 20. Failure of Macrolide Antibiotic Treatment in Patients with Bacteremia Due to Erythromycin-Resistant S. pneumoniae <ul><li>Matched case-control study at 4 hospitals: </li></ul><ul><ul><li>bacteremic pneumococcal infection </li></ul></ul><ul><ul><li>case patients ( n = 86)--erythromycin-I or -R S. pneumoniae </li></ul></ul><ul><ul><li>controls ( n = 141)--erythromycin-susceptible S. pneumoniae </li></ul></ul><ul><li>Taking a macrolide at time blood culture obtained: </li></ul><ul><ul><li>18/76 (24%) cases vs. 0/136 controls ( P <<0.001) </li></ul></ul><ul><li>Low-level-R efflux/M phenotype ( mef ): </li></ul><ul><ul><li>5/21 (24%) cases vs. 0/40 controls ( P = .002) </li></ul></ul><ul><li>Breakthrough bacteremia during macrolide Rx: </li></ul><ul><ul><li> risk among patients infected with an erythromycin-R pneumococcus </li></ul></ul><ul><ul><li>associated with both efflux and methylase mechanism </li></ul></ul>Lonks, JR, et al. Clin Infect Dis 2002;35:556-64
    21. 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
    22. 22. Declining Susceptibility of S. pneumoniae to Levofloxacin <ul><li>Between 1997 and 2002, 26 US hospitals collected susceptibility data for community-acquired S pneumoniae isolates </li></ul><ul><li>6 FQs tested: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, ofloxacin, and trovafloxacin </li></ul><ul><li>Increase in levofloxacin use associated with decreased susceptibility to S pneumoniae across all geographical regions </li></ul><ul><li>Levofloxacin MIC 90 1.0; range <0.5 to >4.0 </li></ul>Bhavnani SM et al. ICAAC 2003, Chicago, Ill. Abstract A 2017. 50%  0.4 to >3.0 Southwest  0.4 to 1.5-3.0 Levofloxacin use increase (Rx/10 0 persons) 126% West MIC increase
    23. 23. Pathophysiology of Acute Maxillary Sinusitis <ul><li>Ostial obstruction is a primary factor </li></ul><ul><ul><li> pO2 </li></ul></ul><ul><ul><li> Clearance of debris </li></ul></ul><ul><li>Predisposing conditions </li></ul><ul><ul><li>Allergic rhinitis </li></ul></ul><ul><ul><li>Upper respiratory infections </li></ul></ul><ul><ul><li>Malformations </li></ul></ul><ul><ul><li>Polyps </li></ul></ul><ul><ul><li>Septal deviation </li></ul></ul><ul><ul><li>Foreign bodies </li></ul></ul><ul><ul><li>Tumors </li></ul></ul><ul><ul><li>Upper tooth infections </li></ul></ul>
    24. 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. 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. 26. Plain Radiograph and CT Scans of the Paranasal Sinuses Piccirillo, J. F. N Engl J Med 2004;351:902-910
    27. 27. Various Signs and Symptoms Used to Predict the Presence of Sinusitis Piccirillo, J. F. N Engl J Med 2004;351:902-910
    28. 28. Principles of Appropriate Antibiotic Use for Acute Sinusitis in Adults Snow V, et al, Ann Intern Med 2001;134:495-7. <ul><li>Most cases of acute rhinosinusitis in ambulatory care are caused by viral URIs </li></ul><ul><li>Viral and bacterial rhinosinusitis are difficult to differentiate on clinical or radiographic grounds </li></ul><ul><li>Clinical Dx of bacterial rhinosinusitis should be reserved for patients with Sx >7 days </li></ul><ul><li>Sinus radiography is not routinely recommended </li></ul><ul><li>Acute bacterial sinusitis does not require antimicrobial treatment when symptoms are mild to moderate: </li></ul><ul><ul><li>Up to 2/3 of patients improve with symptomatic management </li></ul></ul><ul><li>Patients with severe or moderate persistent symptoms should be treated with and antimicrobial </li></ul>
    29. 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
    30. 30. 30 y.o. female with HSP and chronic nasal discharge <ul><li>30 yo F </li></ul><ul><li>Henoch Schonlein purpura, Dx 2001 </li></ul><ul><ul><li>CellCept 500 bid </li></ul></ul><ul><ul><li>prior prednisone </li></ul></ul><ul><li>>12 mths Hx: </li></ul><ul><ul><li>anosmia, altered taste, post nasal drip, sinus pressure </li></ul></ul>
    31. 31. Chronic Sinusitis: History <ul><li>Primary symptom: </li></ul><ul><ul><li>nasal congestion or obstruction; duration >6-12 wks </li></ul></ul><ul><li>Secondary symptoms: </li></ul><ul><ul><li>pain, pressure, and postnasal discharge. </li></ul></ul><ul><li>Symptoms are poorly localized and mild: </li></ul><ul><ul><li>may be extremely difficult to recognize. </li></ul></ul><ul><li>In children: </li></ul><ul><ul><li>purulent rhinorrhea with or without postnasal drip. </li></ul></ul><ul><li>Cough and occasional wheezing episodes. </li></ul>
    32. 32. Chronic Sinusitis: Therapy <ul><li>Sinus irrigation: </li></ul><ul><ul><ul><li>buffered saline (e.g., Sinus Rinse--NeilMed) </li></ul></ul></ul><ul><ul><ul><li>antimicrobial, betadine, acetic acid </li></ul></ul></ul><ul><ul><ul><li>at least BID </li></ul></ul></ul><ul><li>Decongestants: </li></ul><ul><ul><ul><li>topical, systemic </li></ul></ul></ul><ul><li>Corticosteroids: </li></ul><ul><ul><ul><li>topical, systemic </li></ul></ul></ul><ul><li>Surgery </li></ul>
    33. 33. A 15-year-old boy with sinusitis causing right proptosis, telecanthus, and malar flattening
    34. 34. Allergic Fungal Sinusitis (AFS) <ul><li>~ 5-10% of patients with chronic rhinosinusitis have AFS. </li></ul><ul><li>History of atopy: </li></ul><ul><ul><li>~2/3 allergic rhinitis and 50% asthma. </li></ul></ul><ul><ul><li>90% elevated specific IgE to one or more fungal antigens. </li></ul></ul><ul><li>Geography: </li></ul><ul><ul><li>temperate regions of relatively high humidity </li></ul></ul><ul><ul><li>US--most commonwithin the Mississippi basin, the Southeast, and the Southwest. </li></ul></ul><ul><li>Demographics: </li></ul><ul><ul><li>Adolescents and young adults; mean age at Dx--21.9 years </li></ul></ul><ul><ul><li>M/F ratio ~50/50 </li></ul></ul>
    35. 35. AFS Lab Studies <ul><li>Total IgE: </li></ul><ul><ul><li>> 1000 U/mL (normal, <50 U/mL). </li></ul></ul><ul><ul><li>indicator of AFS clinical activity. </li></ul></ul><ul><li>RAST versus skin testing </li></ul><ul><ul><li>positive skin tests and in vitro (RAST) responses to fungal and nonfungal antigens. </li></ul></ul><ul><ul><li>broad sensitivity to a number of fungal and nonfungal antigens. </li></ul></ul><ul><ul><li>generally, only a single fungus is isolated by culture of allergic fungal mucin </li></ul></ul><ul><li>Nonspecific allergy testing </li></ul><ul><ul><li>Gell and Coombs type I hypersensitivity </li></ul></ul>
    36. 36. AFS Treatment <ul><li>Corticosteroids: </li></ul><ul><ul><li>oral, intranasal </li></ul></ul><ul><li>Immunotherapy: </li></ul><ul><ul><li>RAST or quantitative skin test: </li></ul></ul><ul><ul><ul><li>typical panel of nonfungal antigens </li></ul></ul></ul><ul><ul><ul><li>all relevant molds (fungi) available. </li></ul></ul></ul><ul><ul><li>Duration of Rx--3-5 years. </li></ul></ul><ul><li>Antifungal therapy: </li></ul><ul><ul><li>systemic, topical. </li></ul></ul><ul><li>Surgery </li></ul>
    37. 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
    38. 38. New Strains of Bacteria and Exacerbations of COPD <ul><li>The role of bacterial pathogens in AECB is controversial </li></ul><ul><li>Studied 81 outpatients with COPD over 56 months </li></ul><ul><ul><li>collected clinical information and sputum samples monthly and during exacerbations </li></ul></ul><ul><ul><li>performed molecular typing of sputum isolates </li></ul></ul><ul><li>1975 clinic visits, 374 for AECB </li></ul><ul><li>Risk of exacerbation: new (33.0%) vs. no new strains (15.4%); (RR = 2.15) </li></ul><ul><li>New strain of H. influenzae, M. catarrhalis, or S. pneumoniae increased risk of an exacerbation </li></ul><ul><li>Supports the causative role of bacteria in AECB </li></ul>Sethi, S. et al. N Engl J Med 2002;347:465-471
    39. 39. Role of Antimicrobial Therapy in AECB <ul><li>Treatment: 1st Line </li></ul><ul><li>Fluoroquinolone </li></ul><ul><li> -lactam/  -lactamase inhibitor </li></ul><ul><li>Alternative Treatment </li></ul><ul><li>May require parenteral Rx </li></ul><ul><li>Consider referral to specialist; </li></ul><ul><li>hospitalization </li></ul>Balter MS et al. Can Respir J. 2003;10:3B-32B. Likely Pathogens H influenzae Haemophilus spp M catarrhalis S pneumoniae Klebsiella spp Other GNB Probability of  -lactam resistance Anthonisen Type 1 Increased sputum volume Increased sputum purulence Increased dyspnea Complicated FEV 1 < 50% > 4 AECB/y Cardiac disease Use of home O 2 Chronic oral steroid use Antibiotic use in the past 3 mo
    40. 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
    41. 41. Bacterial Pharyngitis: GABHS <ul><li>Group A  -hemolytic streptococci (GABHS)/ S pyogenes </li></ul><ul><ul><li>Most common bacterial cause </li></ul></ul><ul><li>Accounts for approximately 15% –30% of all pediatric and adult pharyngitis cases </li></ul><ul><ul><li>Affects primarily school-aged children </li></ul></ul><ul><li>Peak incidence: winter to early spring </li></ul>Bisno. N Engl J Med. 2001;344:205-211.
    42. 42. Clinical Predictors <ul><li>Physicians, are not able to reliably predict which patients will have a positive throat culture for GAS </li></ul><ul><ul><li>Sensitivity (55-74%) and specificity (58-76%) </li></ul></ul><ul><li>Centor criteria: tonsillar exudates, tender anterior cervical adenopathy, fever by history, absence of cough </li></ul><ul><li>3 of 4 criteria: PPV 40 to 60 %; < 1 of criteria: NPV 80% </li></ul><ul><ul><li>Sensitivity and specificity: 75 % vs. throat cultures </li></ul></ul><ul><li>Some consider the clinical criteria to be too liberal: </li></ul><ul><ul><li>overtreatment of 50 % </li></ul></ul><ul><ul><li>restrict Rx to those with positive rapid antigen testing (RAT) or culture </li></ul></ul>
    43. 43. Throat Culture vs Rapid Antigen Detection Tests <ul><li>Throat culture </li></ul><ul><ul><li>Gold standard for diagnosis of GABHS </li></ul></ul><ul><ul><li>Sensitivity: 90% – 95% </li></ul></ul><ul><ul><li>Throat swab: both tonsils and posterior pharyngeal wall </li></ul></ul><ul><ul><li>Results: 24 hours </li></ul></ul><ul><li>Rapid antigen detection tests </li></ul><ul><ul><li>Rapid results </li></ul></ul><ul><ul><li>More expensive than culture </li></ul></ul><ul><ul><li>Specificity:  95% </li></ul></ul><ul><ul><li>Sensitivity: 80% – 90% </li></ul></ul><ul><ul><li>Negative result: confirm with blood agar-plate culture </li></ul></ul>GABHS = Group A  -hemolytic streptococci. Bisno et al. Clin Infect Dis . 1997;25:574-583.
    44. 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 – – + +
    45. 45. GABHS Pharyngitis: Principles of Antimicrobial Use <ul><li>GABHS diagnosis based on </li></ul><ul><ul><li>Epidemiologic and clinical features </li></ul></ul><ul><ul><li>Laboratory tests </li></ul></ul><ul><li>Antibacterial medication should not be given to a child with pharyngitis in the absence of definitively diagnosed GABHS or other bacterial infection </li></ul><ul><li>Penicillin remains the drug of choice for treating GABHS </li></ul>GABHS = Group A  -hemolytic streptococci. Schwartz et al. Pediatrics . 1998;101(suppl):171-174.
    46. 46. GABHS Pharyngitis: Treatment Options <ul><li>Medication Dose </li></ul><ul><li>First-line </li></ul><ul><li>Oral penicillin V Children: 250 mg bid, tid, or qid x 10 days </li></ul><ul><li>Intramuscular <27 kg body weight: 600,000 units penicillin G benzathine  27 kg body weight: 1.2 million units </li></ul><ul><li>Second-line </li></ul><ul><li>Azithromycin 12 mg/kg/d x 5 days </li></ul><ul><li>Erythromycin 40 mg/kg/d bid, tid, or qid x 10 days* </li></ul><ul><li>Clarithromycin 7.5 mg/kg bid x 10 days † </li></ul><ul><li>Cephalosporin (cephalexin) 12.5 mg/kg or 250 mg, tid or qid x 10 days </li></ul>GABHS = Group A  -hemolytic streptococci. Middleton. Prim Care. 1996;23:719-739; Bisno. N Engl J Med . 2001;344:205-211. Please see full prescribing information. *Up to 1 g/d maximum. † 500 mg/dose maximum.
    47. 47. Management strategies <ul><li>Four reasons to treat a GABHS with antibiotics; none are very compelling in adults: </li></ul><ul><ul><li>To prevent rheumatic fever — treatment works, but this complication has nearly disappeared in North America </li></ul></ul><ul><ul><li>To prevent peritonsillar abscess — again a vanishing complication </li></ul></ul><ul><ul><li>To reduce symptoms — there is a modest (~ 1 day) reduction in symptoms with early treatment </li></ul></ul><ul><ul><li>To prevent transmission — this is important in pediatrics due to extensive exposures but not in adults </li></ul></ul>
    48. 48. Recommendations <ul><li>Empirically treat patients who have all four clinical criteria </li></ul><ul><li>Do not treat with antibiotics or perform diagnostic tests on patients with zero or one criterion. </li></ul><ul><li>Perform RAT on those with two or three criteria and use antibiotic treatment only for patients with positive RAT results. </li></ul><ul><li>Another approach is to treat empirically those adults with three or four of the clinical criteria </li></ul>
    49. 49. Therapy <ul><li>Penicillin--remains first-line therapy for GAS infections </li></ul><ul><ul><li>Pen V 500 tid for 10 days </li></ul></ul><ul><ul><li>benzanthine PCN G 300,000 units + procaine IM </li></ul></ul><ul><ul><li>5-30% Rx failure rate </li></ul></ul><ul><li>Erythromycin--alternative if PCN-allergic </li></ul><ul><li>Empiric, broad spectrum antibiotic therapy for the treatment of sore throat: </li></ul><ul><ul><li>e.g., newer macrolides, cephalosporins, or Augmentin </li></ul></ul><ul><ul><li>increased cost and potential to increase antibiotic resistance among respiratory pathogens </li></ul></ul>
    50. 50. <ul><li> </li></ul><ul><li>Outcome* Azithromycin Penicillin V P Value </li></ul><ul><li>Clinical success † Day 14 98% (178) 87% (188) <0.001 Day 30 96% (170) 81% (165) 0.001 </li></ul><ul><li>Bacterial eradication Day 14 95% (176) 77% (187) <0.001 Day 30 80% (172) 74% (165) 0.245 </li></ul>Azithromycin vs Penicillin V (Trial A): Clinical and Bacteriologic Efficacy Still. Pediatr Infect Dis J. 1995;14:S57-S61. *Evaluable patients (n=366). † Cure + improvement.