1. Journal Club Updates in Infectious Diseases, Sept 2013 Dr. Katy Thompson Preceptor: Dr. David Coleman

3. Case #1 54 yo F presents with 8 days of runny nose, productive of yellow purulent secretions, and maxillary tenderness Which medications would you offer? How would you explain your medication choice to the patient?

4. 1/5 antibiotics in US is given for sinusitis To limit resistance, this antibiotic use should be evidence-based

5. Amoxicillin for Acute Rhinosinusitis RCT 166 adults Uncomplicated, acute rhinosinusitis. Definition: Maxillary pain or tenderness Purulent nasal secretions Rhinosinusitis symptoms for 7-28 days 10 community-based PCP offices

6. Amoxicillin for Acute Rhinosinusitis All patients received 1 week supply of supportive tx for pain, fever, cough, nasal congestion: Tylenol 500 mg q6h PRN pain, fever Guaifenesin 600 mg q12h Dextromethorphan/guaifenesin 10 mL q4-6h Pseudoephedrine 120 mg q12h 0.65% saline nasal spray Treatment for 10 days: Amoxicillin 500 mg tid Vs. Placebo

7. Amoxicillin for Acute Rhinosinusitis Outcome: Symptomatic improvement- Y/N SNOT16 = Sinonasal Outcome Test-16 Zero = no problem to 3 = severe problem Need to blow nose Reduced productivity Ear fullness Headache Sneezing

8. Amoxicillin for Acute Rhinosinusitis Result: Symptomatic improvement: At Days 3 and 10, symptomatic improvement was the same for both placebo and Amoxicillin groups (34% vs. 37%, 78% vs. 80%) However, at day 7, more people in the Amoxicillin group reported feeling better 56% vs 74%.

9. Amoxicillin for Acute Rhinosinusitis Result: Change in SNOT-16 score from day zero: Day 3: 0.59 (Amox) vs. 0.54 (Placebo) Day 7: 1.06 (Amox) vs. 0.86 (Placebo) p-value 0.2 Day 10: 1.23 (Amox) vs. 1.20 (Placebo)

10. Amoxicillin for Acute Rhinosinusitis Limitations?

11. Limitations No stratification by fever (though did stratify by sx severity) Only based on one antibiotic Time of year – allergies affecting results Adherence to antibiotics Bias in who’s performing study- academic vs. industry Clinical versus statistical significance

12. Case #1 54 yo F presents with 8 days of runny nose, productive of yellow purulent secretions, and maxillary tenderness Which medications would you offer? How would you explain your medication choice to the patient?

14. Case #2 68M with HTN, DM, CHF presents due to a cough for 2 weeks. She is requesting a Z pack. What do you tell her?

15. Azithromycin is the most commonly prescribed antibiotic in the U.S.

16. Azithromycin and CV Death Tennessee Medicaid Program All patients 1992-2006 prescribed Azithro Excluded persons at immediate high risk of death from other causes Ages 30-74 Control groups: Those taking Amoxicillin or similar patients not taking antibiotic

17. Azithromycin and CV Death Azithromycin – 347,795 Amoxicillin – 1,348,672 No Rx – 1,391,180

18. Azithromycin and CV Death Endpoint: CV death Death from any cause

19. Azithromycin and CV Death 5-day treatment course Estimated 47 additional CV deaths / 1 million tx courses Sudden cardiac deaths Azithro – 22 people died (65 sudden cardiac deaths / 1 million tx courses) Amox – 29 people died (22 sudden cardiac deaths/ 1 million tx courses) No Rx – 33 people died (24 sudden cardiac deaths/ 1 million 5- day periods) Among highest CV risk group, 245 / 1 million tx courses

21. Azithromycin and CV Death Cautions: Relative risk vs. absolute risk Retrospective administrative databases- incomplete clinical information

22. Case #2 68M with HTN, DM, CHF presents due to a cough for 2 weeks. She is requesting a Z pack. What do you tell her?

24. Case #3 ED patient, 25F presents for STD check. Develops chest pain, admitted for rule out MI. They sent a urine culture, which returns >100,000 CFUs of E.coli. What do you do?

25. Asymptomatic Bacteruria Relevance Studies showing that if you have asymptomatic bacteruria, you’re more likely to develop a symptomatic UTI

26. Asymptomatic Bacteruria 18 - 40 years old Sexually active with 1 partner over the past 12 months One symptomatic UTI treated in past 12 months Currently asymptomatic With urine culture with >= 10 5 CFUs on 2 consecutive specimens

27. Asymptomatic Bacteruria Randomized to receive antibiotic or not (369 women vs. 330) No placebo used Pts returned at 3, 6, and 12 months for repeat urine cultures Asked to return sooner if symptoms

28. Asymptomatic Bacteruria Symptomatic UTIs 3 months Untreated 3.5% vs. treated 8.8% 6 months Untreated 7.6% vs. treated 29.7% 12 months Untreated 14.7% vs. treated 73.1%

29. Asymptomatic Bacteruria Limitations?

30. Asymptomatic Bacteruria Cautions: Limited study population STD symptoms vs. UTI symptoms

31. Asymptomatic Bacteruria Distortion of native ecology by giving antibiotics Antibiotic resistance versus virulence

33. Daily Post-Exposure Ppx in HIV Discordant Couples 4747 serodiscordant couples From Kenya and Uganda Followed for 36 months RTC, double-blind, placebo-controlled Studied the seronegative partner: (62% males) 1584 people took tenofovir 1579 took tenofovir-emtricitabine 1584 took placebo

34. Daily Post-Exposure Ppx in HIV Discordant Couples All participants got: HIV-1 testing with counseling before and after Individual and couples risk-reduction counseling Screening and Tx for other STDs Free condoms with training and counseling Referral for male circumcision and PEP Offered Hep B vaccination

35. Daily Post-Exposure Ppx in HIV Discordant Couples Endpoint: Seropositivity in partners previously HIV-negative 17 infections in the tenofovir group (0.65/100 person- years) 13 in the tenofovir-emtricitabine group (0.50/100 person-years) 52 in the placebo group (1.99/100 person-years)

36. Daily Post-Exposure Ppx in HIV Discordant Couples What’s wrong with this study?

37. Daily Post-Exposure Ppx in HIV Discordant Couples What’s wrong with this study? Ethics Strong emphasis on adherence- monthly visits with seronegative partner and pill counts Limited study population- only heterosexual Safety of Tenofovir in pregnancy, renal function, breast- feeding, bone mineral density

38. Daily Post-Exposure Ppx in HIV Discordant Couples BMC Resources: +HOPE prenatal clinic- advice for HIV+ women who are pregnant or want to become pregnant Dr. Margaret Sullivan (sees all concordant or discordant HIV+ patients contemplating pregnancy)

39. Thanks for your attention!