1. Clinical pearls for the treatment of common out- patient infections Meghan Jeffres, PharmD Assistant Professor Department of Clinical Pharmacy University of Colorado Skaggs School of Pharmacy Meghan.Jeffres@ucdenver.edu

2. Disclosures  Meghan Jeffres  I have no relevant financial relationships with commercial interests pertaining to the content presented in this program.

3. Learning Objectives 1. Locate recent infectious diseases guidelines 2. Identify first line treatment of common out- patient infection ( UTI, SSSI, URTI) 3. Determine inappropriate antibiotic choices for common out-patient infections 4. Assess a patient for the need to refer to either an acute care setting or infectious diseases specialist UTI = urinary tract infections; SSSI = skin and skin structure infection; URTI = upper respiratory tract infection

4. Infectious Diseases Guidelines  Repository of most ID guidelines  Infectious Diseases Society of America (IDSA)  www.idsociety.org www.idsociety.org  Categories: Antimicrobial agent, Infection by organ site, Infection by organism  Scope: Bacterial, viral, fungal, and parasitic infections  Free to the public in PDF, HTML, mobile application  Other sites  HIV/AIDs guidelines: http://aidsinfo.nih.gov/http://aidsinfo.nih.gov/  American Association for the Study of Liver Diseases: hepatitis B and C http://www.aasld.orghttp://www.aasld.org

5. Guideline not Edict IDSA guidelines levels of evidence  Level I: ≥ 1 RCT  Level II: ≥ 1 clinical trial  Level III: opinion Arch Intern Med 2011;171:18-22

6. Recent Releases  2013  Antimicrobial Prophylaxis in Surgery  Acute Otitis Media from American Academy of Pediatrics  Surviving Sepsis Campaign  Prosthetic Joint Infections  Vaccination of the Immunocompromised Host  2014  Skin and Soft Tissue Infections  2015  Infective Endocarditis in Adults  Vertebral Osteomyelitis

7. Urinary Tract Infections  US annual incidence  Females: 1,200 cases per 100,000 persons annually  Males: 30 cases per 100,000 persons annually  Recommended reading  2011IDSA Guideline  Acute Uncomplicated Cystitis and Pyelonephritis in Women  Causative pathogens

8. Lesley, 35 yo Female  HPI: Presents to community pharmacy. She drops off a prescription for nitrofurantoin and asks where the AZO is located.  Allergies: NKDA

9. Key questions Can you describe the location of your pain?  Back  Lower abdomen Lower abdomen

10. Cystitis vs. Pyelonephritis  Lower abdominal pain  Cystitis or uncomplicated UTI  1 st line: nitrofurantoin x 5 days or TMP/SMX x 3 days  2 nd line: FQ (ciprofloxacin, levofloxacin) x 3 days  3 rd line: beta-lactam x 7 days  Back or flank pain  Pyelonephritis or complicated UTI  1 st line: FQ (ciprofloxacin, levofloxacin) x 7 days  2 nd line: beta-lactam x 10-14 days or TMP/SMX x 14 days

11. Key questions Are you pregnant? Yes! I’m 5 months. Are you taking any other medications? Yes, prenatal vitamins.

12. UTI Treatment and Pregnancy AntibioticCategorySafety Concern FluoroquinoloneCTendon development concerns TrimethoprimD Facial defects and cardiac abnormalities (first trimester) SulfamethoxazoleC hemolytic anemia in mothers with glucose-6-phosphate dehydrogenase (G6PD) deficiency, jaundice, and kernicterus NitrofurantoinB Neonatal jaundice and mother hemolytic anemia (third trimester) Beta-lactamsBSafest choice

13. Inappropriate Treatment Choices  Cystitis or pyelonephritis  Fecally excreted antibiotics  Moxifloxacin, dicloxacillin  Pyelonephritis, men, or complicated UTI  Nitrofurantoin  Decreased renal function  Nitrofurantoin will be hepatically excreted at CrCl < 50 ml/min  TMP/SMX will form crystals in the kidney at CrCl < 30 ml/min  Common drug-drug interactions  Fluoroquinolones and cations (Al 3+, Ca 2+, Fe 2+, Mg 2+ )  Found in multivitamins, dairy products, supplements  Separate by 2 hours before and after all fluoroquinolones

14. Recognizing Treatment Failure  Recognizing treatment failure  Cystitis or uncomplicated UTIs  Symptom resolution after 24 hours of antibiotics  Should feel cured after 3 days  Pyelonephritis or complicated UTIs  Symptom resolution after 3 days of antibiotics  Should feel cured after 5-7 days  Refer for culture and new antibiotic if symptoms persist longer than expected

15. Lesley, 35 yo Female Known Choices  Cystitis or uncomplicated UTI  Prescription for nitrofurantoin  6 months pregnant  NKDA A. Fill prescription for nitrofurantoin B. Recommend switching to cephalexin C. Recommend switching to ciprofloxacin D. Recommend switching to TMP/SMX

16. Skin and skin structure infections (SSSI) Recommended reading:  IDSA MRSA Guidelines  Table 3  IDSA SSSI Guidelines  Table 2 95% of the increase attributed to cellulitis and abscesses (14.2 million Americans!) Arch Intern Med 2008;168:1585-91. Visits to primary care physicians, hospital clinics, and EDs

17. Ember, 36 yo Female  HPI: Presents to the pharmacy with a prescription for TMP/SMX  PMH: chronic athletes foot  Allergies: Penicillin – hives  Home meds: topical tolnaftate (Tinactin) 1% cream BID PRN

18. Key questions Can you describe your infection?  Red hot skin? Yes © 2006 Colm Anderson

19. Key questions Is there any drainage or abscess? No © 2012 Amrith Raj

20. Skin and skin structure infections (SSSI) CellulitisPurulent SSSI or abscesses Arch Intern Med 1990;150:1907, Scand J Infect Dis 1989;21:537, Arch Intern Med 1988;148:2451, Ped Infect Dis J 1987;6:685, Arch Intern Med 1986;146:295, NEJM 2006,355:666-674

21. SSSI Treatment Options Cellulitis Purulent SSSI  Beta-lactam  Amoxicillin/clavulanate  Dicloxacillin  Cephalexin  Clindamycin  TMP/SMX + beta-lactam  Linezolid  TMP/SMX  Clindamycin  Doxycycline  Linezolid 5 to 10 days of therapy

22. SSSI Inappropriate Treatment Choices CellulitisAbscess  TMP/SMX does not have coverage against GAS (Streptococcus pyogenes)  Doxycycline active against only 50% of GAS pathogens  Any antibiotic  Indications for antibiotics  Cellulitis with abscess  Fever or chills  Associated comorbidities (DM, HIV, immunosuppression)  Extremes of age  Abscess in area difficult to drain completely (face, hand, and genitalia)  Lack of response to incision and drainage alone

23. Recognizing Treatment Failure Have patient (or you) outline the area of redness with pen or marker. If redness goes beyond marked area after 24 hours of antibiotics return to provider. © 2012 Pshawnoah

24. Ember, 35 yo Female Known Choices  Cellulitis, no abscess or drainage  Prescription for TMP/SMX  Allergies: Penicillin – hives A. Fill prescription for TMP/SMX B. Recommend switching to cephalexin C. Recommend switching to clindamycin Links to excellent abscess incision and drainage videos http://www.nejm.org/doi/full/10.1056/NEJMvcm071319 http://www.nejm.org/doi/full/10.1056/NEJMvcm071319 (requires subscription to NEJM) http://www.youtube.com/watch?v=P6BFUk4n2Ig

25. Ember, 35 yo Female Choices A. Continue TMP/SMX B. Recommend switching to cephalexin C. Recommend switching to clindamycin D. Recommend a visit to the ED or urgent care clinic The provider rejects your recommendation and confirms the choice of TMP/SMX for Ember. She returns to the pharmacy after 3 days of antibiotic therapy and now has fever and chills.

26. Progression of GAS skin infections Toxic shock syndrome, necrosis and or gangrene © Piotr Smuszkiewicz, Iwona Trojanowska and Hanna Tomczak

27. El – 14 month old Female  Lesley presents to your pharmacy with a prescription for levofloxacin for an ear infection for her child El  Allergies: KNDA

28. Upper Respiratory Tract Infections (URTI)  Rhinosinusitis (sinusitis)  1 in 7 (13.4%) of American were diagnosed with a sinus infection every year  Women 1.9 fold > Men  Adults aged 45 to 74 years most affected  Otitis media  Children: 80-90% of children by 3 years old  Highest incidence between 6 and 24 months of age  Recommended reading  Acute Otitis Media Guidelines from American Academy of Pediatrics

29. URTI Causative Pathogens Sinusitis, Otitis media Infection location M. catarrhalis 10% H. influenzae 20% S. pneumoniae 20% Data from Rhinosinutitis IDSA guidelines © Elsevier, Inc., Netterimages.com

30. Supportive Care for Viral Infections  Most cases of sinusitis and otitis media will resolve in 7 days  Sinusitis  Normal saline spray  Sinus irrigation  Only use distilled or previously boiled water  Risk of Naegleria fowleri infection  Warm water parasite – causes primary amebic meningoencephalitis  Symptom onset 1-3 days – meningitis like symptoms, AMS  Death within 7 days  Otitis media  Pain control: ibuprofen > APAP > placebo

31. Antibiotic Efficacy Data from Rhinosinutitis IDSA guidelines N Engl J Med 2011;364:116-26 Otitis media

32. Otitis media Treatment Timing Risk of delayed treatment AgeCertain diagnosisUncertain diagnosis <6 moTreat 6 mo - 2 yearsTreat Treat if severe infection; observation if non-severe ≥2 years Treat if severe infection; observation if non-severe Observation Pediatr Infect Dis J 2012;31: 1227–1232 OutcomeDelayed, n=53 Immediate, n=161 Adj p value Clinical improvement48 (91%)155 (96%)0.06 Absent from daycare29 (83%)59 (69%)0.34 Parent absent from work25 (71%)46 (54%)0.27

33. Otitis media Treatment Options  Amoxicillin  Except if patient has risk factors for amoxicillin resistant pathogens  Children who were treated with antibiotics in the previous 30 days  Children with concurrent purulent conjunctivitis (usually is caused by beta-lactamase positive H. influenzae)  Amoxicillin/clavulanate  Patients with risk factors or fail amoxicillin therapy  Penicillin allergy  Minor or non-IgE mediated – cephalosporin  Severe or IgE mediated – macrolide  Levofloxacin, moxifloxacin for treatment failures  Avoid in pediatric patients when possible

34. Key Questions Does she also have any drainage from her eyes as well as an ear infection? No © 2008 Tanalai at en.wikipedia.org

35. Key Questions Has she had any antibiotics in the last 30 days? No

36. El – 14 month old Female Known Choices  < 2 years old with otitis media  No conjunctivitis or previous antibiotic use  Prescription for levofloxacin  Allergies: KNDA A. Fill prescription for levofloxacin B. Recommend switching to amoxicillin C. Recommend switching to amoxicillin/clavulanate D. Recommend switching to azithromycin

37. Sinusitis Treatment Options  Per IDSA Guidelines  Amoxicillin/clavulanate  Penicillin allergy  Minor or non-IgE mediated – clindamycin and cefixime  Severe or IgE mediated – levofloxacin  Missing from guidelines  Macrolides – azithromycin, clarithromycin  Moxifloxacin

38. URTI Inappropriate Treatment Options  No gram negative coverage (H. influenzae and M. catarrhalis)  Clindamycin  Poor gram positive coverage (S. pneumoniae)  Ciprofloxacin  High resistance rates against S. pneumoniae  TMP/SMX  Unnecessary utilization of fluoroquinolones in pediatric patients

39. Recognizing Treatment Failure  Sinusitis  Continued symptoms after 10 days of antibiotics  May indicate resistant pathogen or non-bacterial source  Otitis media  Continued symptoms after 5 days of antibiotics  May indicate resistant pathogen  Recurrent AOM – surgical intervention indicated  3 episodes in 6 months or 4 episodes in 1 year, with 1 episode in the preceding 6 months

40. Take Home  UTI  Patients with back pain will often have pyelonephritis and at much higher risk of treatment failure  Refer if symptomatic after 3 days of antibiotic treatment  SSSI  Not providing coverage against GAS (S. pyogenes) for cellulitis is dangerous  Most abscesses do not need antibiotics  URTI – sinusitis, otitis media  Most are viral causes and will resolve in a week  Bacterial pathogens are S. pneumoniae, H. influenzae, and M. catarrhalis – antibiotics need to have both gram positive and gram negative coverage

41. Clinical pearls for the treatment of common out- patient infections Meghan Jeffres, PharmD Assistant Professor Department of Clinical Pharmacy University of Colorado Skaggs School of Pharmacy Meghan.Jeffres@ucdenver.edu