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1. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and AdolescentsBacterial 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

2. About This Presentation These slides were developed using recommendations published in May 2013. 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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 http://www.aidsetc.org www.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 www.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 Shigellaand Campylobacter) • HIV-related alterations in mucosal immunity or intestinal integrity, gastric acid-blocking medications www.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 www.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 www.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-coliCampylobacter species; request special testingfor these if initial evaluation is unrevealing www.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) www.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 resultin oral exposure to feces www.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) www.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 www.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 www.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 www.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: • Levofloxacin750 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 www.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) www.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 for 3-7 days • Azithromycin 500 mg PO QD for 5 days (not recommended if bacteremia) • High rate of TMP-SMX resistance in infections acquired outside the United States www.aidsetc.org

17. Bacterial Enteric Disease: Treatment (7)Shigella spp. (cont.) • Duration of therapy • Gastroenteritis: 7-10 days (5 days for azithromycin) • Bacteremia: ≥14 days • Recurrent infection: up to 6 weeks www.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 • Bacteremia: ciprofloxacin 500-750 mg PO or 400 mgIV Q12H + aminoglycoside www.aidsetc.org

19. Bacterial Enteric Disease: Treatment (9)Campylobacter spp. (cont.) • Duration of therapy • Gastroenteritis: 7-10 days (5 days for azithromycin) • Bacteremia: >14 days • Recurrent bacteremic disease: 2-6 weeks www.aidsetc.org

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

22. Bacterial Enteric Disease: Monitoringand 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 www.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 www.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 www.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 www.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-SMXin 1st trimester (increased risk of birth defects) • Sulfa therapy near delivery may increase risk to newborn of hyperbilirubinemia and kernicterus www.aidsetc.org

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

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