Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Best Practice Pharmacotherapeutics in Primary Care November 12, 2015 Steven C. Johnson M.D.

Objectives • Review common principles of antibiotic selection and dosing. • Describe the pathogenesis of common infectious diseases including sinusitis, bronchitis, pneumonia, and UTIs. • Illustrate common antibiotic treatment regimens for these diseases using case studies.

Professor of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine

Principles of Antibiotic Use 1. Identify the correct clinical syndrome in patients presenting with signs and symptoms of infection. 2. Identify co-morbidities that will impact etiology and antibiotic choice (e.g. HIV, diabetes, injection drug use, cancer). 3. Recognize common antibiotic resistance patterns at individual institutions. 4. Screen for antibiotic allergy.

Principles of Antibiotic Use 5. Screen for drug-drug interactions using on-line and/or EHR databases. 6. Initial antibiotic therapy is often empiric and published guidelines are helpful in choosing therapy and duration. 7. Antibiotic therapy should be narrowed if a specific etiology is determined. 8. Liberally use local and on-line resources to accurately manage infectious diseases and learn appropriate management.

Resources for Information on Microbiology, Antibiotics, and Infectious Diseases Local Resources • Microbiology Lab – Specimen collection – Interim culture results – Susceptibilities

• Infection Control – Isolation procedures

• Infectious Disease Pharmacists • Infectious Disease Consult Service

On-Line Resources • www.cdc.gov

Case Study 1:

– Comprehensive info for many infections

• www.idsociety.org – Practice guidelines for many infections

• www.aidsinfo.nih.gov – HIV/AIDS info

• Drug-drug interaction databases

Acute Sinusitis

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm

Case Study 1 This is a 34 year old male with stable HIV infection • He presents with a 3 day history of rhinorrhea, nasal congestion, headache, and sore throat. • He denies fever or facial pain. • He reports prior episodes of sinusitis similar to his presentation today. • Medications: tenofovir/emtricitabine/efavirenz • He reports no drug allergies.

Given these findings and HIV infection, antibiotics are indicated in this patient. 1. Yes 2. No 3. I don’t know

Clinical Findings Suggestive of Bacterial Rhinosinusitis

Case Study 1 • Physical Exam: – Afebrile – Mild pharyngeal erythema – No facial tenderness – Lungs clear

• Laboratory data: – Recent CD4 cell count 670 cells/mm3 – Recent HIV viral load undetectable – WBC today 9800

Acute Rhinosinusitis • Inflammation/infection involving the nasal mucosa and sinus cavities. • 90-98% of cases are viral in etiology. • 2-10% are bacterial. • Symptoms of sinusitis are one of the most frequent reasons for office visits. • Antibiotics are frequently prescribed but seldom necessary.

Sinus Anatomy

1. Persistent symptoms or signs compatible with sinusitis for > 10 days without evidence of improvement. 2. Severe symptoms or signs of high fever (> 39o C or 102o F) and purulent nasal discharge or facial pain lasting at least 3-4 consecutive days. 3. Worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical URI that lasted 5-6 days and was initially improving. http://www.healthinfo.org.nz/aoraki/sinuses.jpg

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm Antimicrobial Therapy for Acute Bacterial Rhinosinusitis in Adults • Amoxicillin-clavulanate is the recommended initial empiric agent. • Doxycycline is an alternative agent. • Either a respiratory fluoroquinolone or doxycycline can be used in PCN-allergic patients. • Macrolides and trimethoprimsulfamethoxazole are not recommended. • Duration of therapy is 5-7 days.

Adjunctive Therapies in Sinusitis • • • • •

Antimicrobial Therapy Agent

Dosing

Comment

Amoxicillinclavulanate

875/125 mg PO BID or 500/125 mg PO TID

Preferred agent

Doxycycline

100 mg PO BID

Alternative agent. B-lactam allergy. Alternative agent. B-lactam allergy. Alternative agent. B-lactam allergy.

Levofloxacin 500 mg PO daily Moxifloxacin

400 mg PO daily

• Macrolides, trimethoprim-sulfamethoxazole, or second or third-generation oral cephalosporins are not recommended.

Key Guideline

Saline irrigation: recommended Intranasal glucocorticoids: recommended Oral decongestants: not recommended Topical decongestants: not recommended Antihistamines: not recommended

Case Study: Conclusion • Antibiotics were not prescribed given his mild symptoms, short duration, and high CD4 lymphocyte count. • Additional microbiologic studies were not deemed necessary (respiratory PCR tests are expensive). • He recovered without need for additional therapies.

Case Study 2: Acute Bronchitis

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm

Case Study 2 • A 42 year old male presents with a 4 day history of cough, yellow sputum, and nasal and chest congestion. • He has no prior medical history and is on no medications. • Physical Exam: Afebrile, pulse oximetry of 94% on room air, lung exam with scattered wheezes but no rales. • Laboratory data includes a WBC of 11,400. • A chest x-ray is normal.

Which of the following is the best initial empiric antibiotic in this patient? 1. Levofloxacin 750 mg daily x 7 days 2. Azithromycin 500 mg today followed by 250 mg daily for 4 additional days 3. Doxycycline 100 mg BID x 7 days 4. Amoxicillin 500 mg TID x 7 days 5. None of the above

Acute Bronchitis

Acute Bronchitis: An Opportunity for Antimicrobial Stewardship

• Typically self-limited viral upper respiratory infection. • Characterized by cough and sputum production for 1-3 weeks in duration. • Bacterial etiologies are less common but can include Pertussis, Mycoplasma infection or Chlamydia infection. • Influenza, if caught early, could be an opportunity for treatment.

• Acute bronchitis and other upper respiratory infections are one of the most common reasons for clinic visits. • Despite a predominant viral etiology, antibacterial agents are commonly prescribed in this setting. • In addition, many of these antibiotics have a broad spectrum of activity. • The vast majority of patients do not need antibiotics.

Wenzel R and Fowler A, N Engl J Med 2006;355:2125-30.

Pertussis • Highly contagious respiratory infection caused by Bordetella pertussis. • Catarrhal stage of 1-2 weeks followed by paroxysmal cough for 1-6 weeks. • 32,791 reported cases in U.S. in 2014. • Pertussis in infants can be fatal.

Bronchial plugging in a neonate with pertussis pneumonia http://www.vaccineinformation.org/phot os/pertaap001.jpg

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm Pertussis: Clinical Case Definition • Clinical Case Definition: In the absence of a more likely diagnosis, a cough illness lasting ≥2 weeks with one of the following symptoms: – – – –

Paroxysms of coughing, OR Inspiratory "whoop," OR Posttussive vomiting, OR Apnea (with or without cyanosis) (for infants < 1 year only)

Pertussis: Treatment Agent Azithromycin

Dose 500 mg PO on day 1 and then 250 mg PO for 4 days Clarithromycin 500 mg PO BID Erythromycin 500 mg PO QID TrimethoprimOne DS (160/800 Sulfamethoxazole mg) tablet PO BID

Pertussis: Laboratory Diagnosis • Isolation of Bordetella pertussis from clinical specimen • Positive polymerase chain reaction (PCR) for B. pertussis • PCR is available on the respiratory PCR panel available in some facilities

Pertussis: Vaccination

Duration 5 days

• CDC’s Advisory Committee on Immunization Practices (ACIP) recommended in 2005 that adults, aged 19-64, receive Tdap vaccine in place of Td vaccine for one of the booster doses.

7 days 7-14 days 14 days

• New vaccine provides added protection against pertussis, which causes an estimated 600,000 cases per year in adults in this age group. • Booster interval remains 10 years. www.cdc.gov

Antiviral Therapy for Influenza in Adults Agent

Dosing

Adverse Reactions

Oseltamivir

75 mg PO BID for 5 days

Nausea and vomiting

Zanamivir

10 mg (two 5 mg Bronchospasm inhalations) BID for 5 days Peramivir One 600 mg dose IV Allergic reactions are for 15-30 minutes very rare • Therapy is most effective when given within 48 hours of the onset of symptoms. http://www.cdc.gov/flu/professionals/antivirals/antiviral-dosage.htm

Case Study: Conclusion • Given the short duration of symptoms and normal chest x-ray, additional microbiologic studies were not done. • Specifically, he was not tested for pertussis or influenza. • He had persistent symptoms for 2-3 weeks but this is not unusual with viral causes of bronchitis.

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm

Case 3 Case Study 3: Community-Acquired Pneumonia

A 47 year old male with COPD presents to the Emergency Department. • 4 day history of cough productive of yellow sputum, sometimes blood-tinged, SOB, and intermittent fever, maximum 101.4o F • Exam: T 100.4, BP 98/74, resp 20, P 108; lung exam with right anterior rales • Lab: WBC 11200; pulse ox 88% on RA

Which of the following is not a good choice for empiric therapy? 1. Levofloxacin 2. Ceftriaxone with azithromycin 3. Moxifloxacin 4. Clarithromycin 5. Amoxicillinclavulanate with azithromycin

Common Etiologies of CommunityAcquired Pneumonia: Outpatient • • • • •

Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses

IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Common Etiologies of CommunityAcquired Pneumonia: Inpatient (Non-ICU) • • • • • • •

Streptococcus pneumoniae Mycoplasma pneumoniae Chlamydophila pneumoniae Haemophilus influenzae Respiratory viruses Legionella species Aspiration IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm Common Etiologies of CommunityAcquired Pneumonia: Inpatient (ICU) • • • • •

Streptococcus pneumoniae Haemophilus influenzae Staphylococcus aureus Legionella species Gram negative bacilli

IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Less Common Pathogens in Community-Acquired Pneumonia Other Bacteria • CA-MRSA • Legionella • Actinomyces • Nocardia • Pseudomonas • Coxiella • Yersinia pestis • Francisella tularensis • M. tuberculosis

Fungi • Coccidioides • Blastomyces • Histoplasma • Pneumocystis Viruses • Influenza • Adenovirus • RSV • Hantavirus

Pulmonary TB

PCP as the presenting illness in HIV infection

Empiric Antibiotic Therapy for Community-Acquired Pneumonia Clinical Situation Outpatient Treatment, Previously Healthy

Suggested Regimens A.Macrolide (azithromycin, clarithromycin, or erythromycin) or B.Doxycycline

IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Empiric Antibiotic Therapy for Community-Acquired Pneumonia Clinical Situation Suggested Regimens Outpatient Treatment, A.Respiratory Presence of cofluoroquinolone morbidities such as (moxifloxacin, chronic heart, lung, liver, gemifloxacin, or or renal disease; diabetes levofloxacin) or mellitus; alcoholism; B.β-Lactam plus a malignancies; asplenia; macrolide immunosuppressed; or use of antimicrobials in the previous 3 months IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm Empiric Antibiotic Therapy for Community-Acquired Pneumonia Clinical Situation Inpatient, Non-ICU Treatment

Suggested Regimens A.Respiratory fluoroquinolone or B.β-Lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus a macrolide

IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Case 3 Conclusion

Empiric Antibiotic Therapy for Community-Acquired Pneumonia Clinical Situation Inpatient, ICU Treatment

Suggested Regimens β-Lactam plus either a macrolide or a respiratory fluoroquinolone

IDSA/ATS Guidelines for CAP in Adults. CID 2007;44:S27-S72

Case 3: Pneumococcus on Gram Stain

• He was initially placed on azithromycin and ceftriaxone. • Sputum gram stain revealed gram positive diplococci . • Sputum culture + for S. pneumoniae. • Fever and hypoxia resolved over 2 days. • He was discharged home on amoxicillin to complete a 14 day course.

Invasive Pneumococcal Disease in the United States

MMWR, October 12, 2012, Vol. 61, No. 40

Antibiotic Resistance in Pneumococcus • Resistance to β-Lactam antibiotics is due to genetic mutations that lead to alterations in penicillin-binding proteins. • Up to 15% of pneumococci in invasive infections (e.g. meningitis, bacteremia) may be resistant to penicillin. • In cases of serious or life-threatening infection, empiric therapy with vancomycin and ceftriaxone is often initiated until susceptibilities are known.

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm

Pneumococcal Polysaccharide Vaccine • 23 purified capsular polysaccharide antigens of S. pneumoniae • 1 dose • Booster interval: 5 years in some patients • Contraindications: prior adverse reaction to the vaccine • Side effects: local arm soreness in 50%, other reactions very uncommon

Pneumococcal Conjugate Vaccine • Originally a pediatric vaccine • Pneumococcal polysaccharide conjugated to nontoxic diphtheria toxin • PCC7 available in 2000 • Replaced by PCV13 in 2010 • 12 of the serotypes contained in PCV13 are present in PPSV23

www.cdc.gov

Changing Epidemiology of Invasive Pneumococcal Disease Among Older Adults in the Era of Pediatric Pneumococcal Conjugate Vaccine

Incidence of Invasive Pneumococcal Disease (# Cases/100,000)

• Background: Pediatric pneumococcal conjugate vaccine licensed in 2000; initially with 7 serotypes

45

• Objective: To determine incidence of invasive pneumococcal disease among adults aged 50 or older

30

• Design: Population-based surveillance of invasive pneumococcal disease performed in 8 US geographic areas from 1998-2003

15

• Outcome: Incidence of pneumococcal disease by serotype and other characteristics. Lexau et al, JAMA 2005;294:2043

40 35 Overall

25

7 PCV Serotypes

20

Non-vaccine serotypes

10 5 0 1998-1999

2002-2003

Overall incidence declined by 28%; the incidence of the 7 serotypes contained in the pneumococcal conjugate vaccine declined by 55%

Key Guidelines • Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007; 44:S27–72. Available at www.idsociety.org. Update in progress. • Guidelines for the Management of Adults with Hospitalacquired, Ventilator-associated, and Healthcare-associated Pneumonia. Am J Respir Crit Care Med Vol 171. pp 388– 416, 2005. Available at www.idsociety.org. Update in progress.

Case Study 4: Urinary Tract Infection

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm

Case Study 4 • A 27 year old female presents to urgent care. • She notes 2-3 days of dysuria. • She is sexually active with one sexual partner. • She is currently on no medications. • She reports no known drug allergies. • Urinalysis reveals pyuria.

Which of the following would not be an appropriate empiric therapy? 1. 2. 3. 4. 5.

Case Study 4: Continued • Physical Examination: afebrile, normal cardiac and lung examinations, mild suprapubic tenderness • Urinalysis: 30 WBCs, 10 RBCs, trace protein, trace nitrate • Urine culture pending

Treatment Regimens and Expected Efficacy for Acute Uncomplicated Cystitis

Levofloxacin Nitrofurantoin Amoxicillin Fosfomycin Trimethoprim-sulfamethoxazole

www.idsociety.org

Case Study 4: Continued • Urine culture grew mixed flora consistent with skin flora. • Urine Nucleic acid amplification tests (NAAT) – Positive for Chlamydia – Negative for GC

Chlamydial Infections in the United States • One of the most commonly reported infectious diseases in the U.S. • 1,401,906 infections reported in 2013 (447 cases per 100,000). • A common cause of PID and infertility. http://www.cdc.gov/std/stats13/chlamydia.htm

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm Chlamydia — Rates of Reported Cases by State, United States and Outlying Areas, 2013

Treatment of Chlamydial Infections in Adults and Adolescents Infection

Recommended Regimen

Alternative Regimens

Chlamydial • Azithromycin 1 gm • Erythromycin 500 mg infection PO x 1 dose or PO QID x 7 days • Doxycycline 100 • Erythromycin ES 800 mg PO BID x 1 mg PO QID x 7 days week • Levofloxacin 500 mg PO QD x 7 days • Ofloxacin 300 mg PO BID x 7 days http://www.cdc.gov/std/stats13/slides.htm

Gonococcal Infections in the United States

CDC. Sexually Transmitted Diseases Guidelines 2015, MMWR 2015;64(No. RR-3):1-140

Gonorrhea — Rates of Reported Cases by State, United States and Outlying Areas, 2013

• 333,004 reported cases in 2013 • Can cause genitourinary, rectal, pharyngeal, or disseminated infection • Antibiotic resistance is a growing problem http://www.cdc.gov/std/stats13/slides.htm

Antimicrobial Drugs Used to Treat GC Among Participants, Gonococcal Isolate Surveillance Project (GISP), 1988–2013

Neisseria gonorrhoeae — Percentage of Isolates, with Penicillin, Tetracycline, and/or Ciprofloxacin Resistance, Gonococcal Isolate Surveillance Project (GISP), 2013

Ceftriaxone 125 mg

http://www.cdc.gov/std/stats13/slides.htm

http://www.cdc.gov/std/stats13/slides.htm

Infectious Diseases: Sinusitis, Acute Bronchitis, Pneumonia, and UTIs Steven C. Johnson M.D. Thursday November 12, 2015 4:15 - 5:30 pm Treatment of Gonococcal Infections in Adults and Adolescents Infection

Recommended Alternative Regimens Regimen Uncomplicated Ceftriaxone 250 • Cefixime 400 mg PO + gonococcal mg IM x 1 dose + azithromycin 1 gm PO infections of the azithromycin 1 • gemifloxacin 320 mg cervix, urethra, gm PO x 1 dose PO + azithromycin 2 or rectum gm PO Uncomplicated Same regimen as Unclear. Pharyngeal gonococcal above gonorrhea is more infection of the difficult to eradicate than pharynx other sites of infection.

Case Study 4: Conclusion • The urine pregnancy test was negative. • She was treated with 1 gm of azithromycin for 1 dose. • She was also screened for syphilis and HIV infection; these tests were negative. • Her symptoms resolved. • Her partner was referred for testing.

Sexually Transmitted Diseases Treatment Guidelines, 2015

Key Guideline for UTI

Key Guideline for STD Treatment

Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015;64(No RR-3):1-137