1. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Bacterial Enteric Disease Slide Set Prepared by the AETC National Resource Center based on recommendations from the CDC, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America November 2014www.aidsetc.org

2. November 2014www.aidsetc.org 2 About This Presentation These slides were developed using recommendations published in May 2013 and updated in November 2014. The intended audience is clinicians involved in the care of patients with HIV. Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. – AETC National Resource Center

3. November 2014www.aidsetc.org 3 Bacterial Enteric Disease: Epidemiology  Higher incidence of gram-negative enteric infections among HIV-infected patients  Risk greatest if CD4 <200 cells/µL or AIDS  Risk decreased with ART  Most commonly cultured bacteria:  Salmonella  Shigella  Campylobacter  E coli  Clostridium difficile

4. November 2014www.aidsetc.org 4 Bacterial Enteric Disease: Epidemiology (2)  Source usually ingestion of contaminated food or water  Other risks:  Oral-fecal exposure through sexual activity (especially Shigella and Campylobacter)  HIV-related alterations in mucosal immunity or intestinal integrity, gastric acid-blocking medications

5. November 2014www.aidsetc.org 5 Bacterial Enteric Disease: Clinical Manifestations  Three major clinical syndromes  Self-limited gastroenteritis  Diarrheal disease +/- fever, bloody diarrhea, weight loss, possible bacteremia  Bacteremia associated with extraintestinal involvement, with or without GI illness

6. November 2014www.aidsetc.org 6 Bacterial Enteric Disease: Clinical Manifestations (2)  Severe diarrhea: ≥6 loose stools per day, with our without other signs/symptoms  In HIV infection:  Greater risk of more serious illness with greater immunosuppression  Relapses may occur after treatment  Recurrent Salmonella bacteremia is an AIDS- defining illness

7. November 2014www.aidsetc.org 7 Bacterial Enteric Disease: Diagnosis  History: exposures; medication review; diarrhea frequency, volume, presence of blood; associated signs/symptoms (eg, fever)  Physical exam including temperature, assessment of hydration and nutritional status  Stool and blood cultures  Obtain blood cultures in patients with diarrhea and fever  Routine stool culture may not identify non-jejuni non- coli Campylobacter species; request special testing for these if initial evaluation is unrevealing

8. November 2014www.aidsetc.org 8 Bacterial Enteric Disease: Diagnosis (2)  C difficile toxin or PCR  If recent or current antibiotic exposure, cancer chemotherapy, recent hospitalization, residence in long-term care facility, CD4 <200 cells/µL, acid- suppressive medications, moderate-severe community-acquired diarrhea  Endoscopy  If stool studies and blood culture are nondiagnostic, or if treatment for an established diagnosis fails  May diagnose nonbacterial causes (eg, parasites, CMV, MAC, noninfectious causes)  Consider STDs (eg, rectal infections caused by lymphogranuloma venereum or N gonorrhoeae)

9. November 2014www.aidsetc.org 9 Bacterial Enteric Disease: Preventing Exposure Advice to patients:  Handwashing:  After potential contact with feces, pets or other animals, gardening/ contact with soil; before preparing food, eating; before and after sex  For prevention of enteric infection, soap and water preferred over alcohol-based cleansers (these do not kill C difficile spores, are partly active against norovirus and Cryptosporidium)  Sex:  Avoid unprotected sexual practices that might result in oral exposure to feces

10. November 2014www.aidsetc.org 10 Bacterial Enteric Disease: Preventing Disease  Antimicrobial prophylaxis usually not recommended, including for travellers  Risk of adverse reactions, resistant organisms, C difficile infection  Can be considered in rare cases, depending on level of immunosuppression and the region and duration of travel  Fluoroquinolone (FQ) or rifaximin  TMP-SMX may give limited protection (eg, if pregnant or already taking for PCP prophylaxis)

11. November 2014www.aidsetc.org 11 Bacterial Enteric Disease: Treatment  Treatments usually the same as in HIV- uninfected patients  Give oral or IV rehydration if indicated  Advise bland diet and avoidance of fat, dairy, and complex carbohydrates  Effectiveness and safety of probiotics or antimotility agents not adequately studied in HIV- infected patients  Avoid antimotility agents if concern about inflammatory diarrhea

12. November 2014www.aidsetc.org 12 Bacterial Enteric Disease: Treatment (2) Empiric Therapy  CD4 count and clinical status guide initiation and duration of empiric antibiotics, eg:  CD4 count >500 cells/µL with mild symptoms: only rehydration may be needed  CD4 count 200-500 cells/µL and symptoms that compromise quality of life: consider short course of antibiotics  CD4 count <200 cells/µL with severe diarrhea, bloody stool, or fevers/chills: diagnostic evaluation and antibiotics

13. November 2014www.aidsetc.org 13 Bacterial Enteric Disease: Treatment (3) Empiric Therapy (cont.)  Preferred: ciprofloxacin 500-750 mg PO (or 400 mg IV) Q12H  Alternative: ceftriaxone 1 g IV Q24H or cefotaxime 1 g IV Q8H  Adjust therapy based on study results  Traveler’s diarrhea: consider possibility of antibiotic resistance

14. November 2014www.aidsetc.org 14 Bacterial Enteric Disease: Treatment (4) Salmonella spp.  In HIV infection, treatment recommended, because of high risk of bacteremia and mortality in HIV-infected patients  Preferred:  Ciprofloxacin 500-750 mg PO (or 400 mg IV) Q12H  Alternative:  Levofloxacin 750 mg PO or IV Q24H  Moxifloxacin 400 mg PO or IV Q24H  TMP-SMX PO or IV, if susceptible  Ceftriaxone (IV) or cefotaxime (IV), if susceptible

15. November 2014www.aidsetc.org 15 Bacterial Enteric Disease: Treatment (5) Salmonella spp. (cont.)  Optimal duration of therapy not defined  Gastroenteritis without bacteremia  CD4 count ≥200 cells/µL: 7-14 days  CD4 count <200 cells/µL: 2-6 weeks  Gastroenteritis with bacteremia  CD4 count ≥200 cells/µL:14 days, longer if persistent bacteremia or complicated infection  CD4 count <200 cells/µL: 2-6 weeks  If bacteremia, monitor closely for recurrence (eg, bacteremia or localized infection)

16. November 2014www.aidsetc.org 16 Bacterial Enteric Disease: Treatment (6) Shigella spp.  Treatment recommended, to shorten duration and possibly prevent transmission  Preferred:  Ciprofloxacin 500-750 mg PO or 400 mg IV Q12H  Alternative (depending on susceptibilities):  Levofloxacin 750 mg PO or IV Q24H  Moxifloxacin 400 mg PO or IV Q24H  TMP-SMX 106/800 mg PO or IV Q12H  Azithromycin 500 mg PO QD for 5 days (not recommended if bacteremia)

17. November 2014www.aidsetc.org 17 Bacterial Enteric Disease: Treatment (7) Shigella spp. (cont.)  High rate of TMP-SMX resistance in infections acquired outside the U.S.; reports of azithromycin resistance in HIV-infected MSM  Duration of therapy  Gastroenteritis: 7-10 days (5 days for azithromycin)  Bacteremia: ≥14 days  Recurrent infection: up to 6 weeks

18. November 2014www.aidsetc.org 18 Bacterial Enteric Disease: Treatment (8) Campylobacter spp.  Optimal treatment in HIV poorly defined  Culture and susceptibility recommended (increasing resistance to FQ)  Mild disease and CD4 >200 copies/µL: may withhold antibiotics unless symptoms persist beyond several days  Mild-moderate disease  Preferred  Ciprofloxacin 500-750 mg PO or 400 mg IV Q12H  Azithromycin 500 mg PO QD for 5 days (avoid if bacteremia)  Alternative (depending on susceptibilities):  Levofloxacin 750 mg PO or IV Q24H  Moxifloxacin 400 mg PO or IV Q24H

19. November 2014www.aidsetc.org 19 Bacterial Enteric Disease: Treatment (9) Campylobacter spp. (cont.)  Bacteremia: ciprofloxacin 500-750 mg PO or 400 mg IV Q12H + aminoglycoside  Duration of therapy  Gastroenteritis: 7-10 days (5 days for azithromycin)  Bacteremia: >14 days  Recurrent bacteremic disease: 2-6 weeks

20. November 2014www.aidsetc.org 20 Bacterial Enteric Disease: Treatment (10) C difficile  Treatment as in HIV-uninfected patients

21. November 2014www.aidsetc.org 21 Bacterial Enteric Disease: Initiating ART  ART expected to decrease risk of recurrent Salmonella, Shigella, and Campylobacter infections  Follow standard guidelines  Consider patient’s ability to ingest and absorb ARV medications  Consider prompt ART initiation if Salmonella bacteremia, regardless of CD4 count (should not be delayed)

22. November 2014www.aidsetc.org 22 Bacterial Enteric Disease: Monitoring and Adverse Effects  Monitor closely for treatment response  Follow-up stool culture not required if clinical symptoms and diarrhea resolve  May be required if public health considerations and state law dictate  IRIS has not been described

23. November 2014www.aidsetc.org 23 Bacterial Enteric Disease: Treatment Failure  Consider follow-up stool culture if lack of response to appropriate antibiotic therapy  Look for other enteric pathogens including C difficile; antibiotic resistance  Consider malabsorption of antibiotics: use IV antibiotics if patient is clinically unstable

24. November 2014www.aidsetc.org 24 Bacterial Enteric Disease: Preventing Recurrence  Salmonella  Secondary prophylaxis should be considered for patients with recurrent Salmonella bacteremia; also might be considered for those with recurrent gastroenteritis (with or without bacteremia) and in those with CD4 count <200 cells/µL and severe diarrhea  This approach is not well established; weigh benefits and risks  Consider stopping secondary prophylaxis if Salmonella infection is resolved, patient is on ART with virologic suppression and CD4 count >200 cells/µL

25. November 2014www.aidsetc.org 25 Bacterial Enteric Disease: Preventing Recurrence (2)  Shigella  Chronic suppressive therapy not recommended for first- time infections  Recurrent infections: extend antibiotic treatment for up to 6 weeks  ART expected to decrease recurrence  Campylobacter  Chronic suppressive therapy not recommended for first- time infections  Recurrent infections: extend antibiotic treatment for 2-6 weeks  ART expected to decrease recurrence

26. November 2014www.aidsetc.org 26 Bacterial Enteric Disease: Considerations in Pregnancy  Diagnosis as with nonpregnant women  Management as with nonpregnant adults, except:  Expanded-spectrum cephalosporins or azithromycin should be first-line therapy for bacterial enteric infections (depending on organism and susceptibility testing)  FQs can be used if indicated by susceptibility testing or failure of first-line therapy (arthropathy in animals; no increased risk of arthropathy or birth defects in humans after in utero exposure)  Avoid TMP-SMX in 1st trimester (increased risk of birth defects)  Sulfa therapy near delivery may increase risk to newborn of hyperbilirubinemia and kernicterus

27. November 2014www.aidsetc.org 27 Websites to Access the Guidelines  http://www.aidsetc.org  http://aidsinfo.nih.gov

28. November 2014www.aidsetc.org 28  This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in June 2013 and updated in November 2014  See the AETC NRC website for the most current version of this presentation: http://www.aidsetc.org About This Slide Set