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

These slides were developed using recommendations published in May 2013 and updated in May 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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 About This Presentation May 2016www.aidsetc.org 2

 Epidemiology  Clinical Manifestations  Diagnosis  Prevention  Treatment  Considerations in Pregnancy Bacterial Enteric Infections May 2016www.aidsetc.org 3

 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 Bacterial Enteric Disease: Epidemiology May 2016www.aidsetc.org 4

 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 Bacterial Enteric Disease: Epidemiology (2) May 2016www.aidsetc.org 5

 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 Bacterial Enteric Disease: Clinical Manifestations May 2016www.aidsetc.org 6

 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 Bacterial Enteric Disease: Clinical Manifestations (2) May 2016www.aidsetc.org 7

 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 Bacterial Enteric Disease: Diagnosis May 2016www.aidsetc.org 8

 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  Antibiotic susceptibility should be performed on all stool samples  Increased rates of resistant and multidrug-resistant Enterobacteriaceae, especially outside the U.S.  Consider possible resistance when prescribing empiric treatment for persons who develop diarrhea or systemic infection while traveling or returning to the U.S. Bacterial Enteric Disease: Diagnosis (2) May 2016www.aidsetc.org 9

 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) Bacterial Enteric Disease: Diagnosis (3) May 2016www.aidsetc.org 10

 Advice to patients:  Handwashing:  After potential contact with feces, pets or other animals, gardening or 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 Bacterial Enteric Disease: Preventing Exposure May 2016www.aidsetc.org 11

 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) Bacterial Enteric Disease: Preventing Disease May 2016www.aidsetc.org 12

 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 Bacterial Enteric Disease: Treatment May 2016www.aidsetc.org 13

 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 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; empiric treatment with ciprofloxacin is reasonable Bacterial Enteric Disease: Treatment (2) May 2016www.aidsetc.org 14

 Empiric Therapy (cont.)  Preferred: ciprofloxacin 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: antibiotic resistance is common outside the U.S.  Consider this when prescribing enteric antibiotics (esp. in travelers to South and Southeast Asia) Bacterial Enteric Disease: Treatment (3) May 2016www.aidsetc.org 15

 In HIV infection, treatment recommended, because of high risk of bacteremia and mortality  Preferred:  Ciprofloxacin mg PO (or 400 mg IV) Q12H  Alternative:  Levofloxacin 750 mg PO or IV Q24H  Moxifloxacin 400 mg PO or IV Q24H  TMP-SMX 160/800 mg PO or IV Q12H, if susceptible  Ceftriaxone 1 g IV Q24H or cefotaxime 1 g IV Q8H, if susceptible Bacterial Enteric Disease: Treatment (4) Salmonella spp. May 2016www.aidsetc.org 16

 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) Bacterial Enteric Disease: Treatment (5) Salmonella spp. (cont.) May 2016www.aidsetc.org 17

 Treatment recommended, to shorten duration and possibly prevent transmission  Preferred:  Ciprofloxacin 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 160/800 mg PO or IV Q12H  Azithromycin 500 mg PO QD for 5 days (not recommended if bacteremia)  Cipro resistance reported, associated with MSM, homelessness, international travel; azithro resistance reported in HIV-infected MSM; high rate of TMP-SMX resistance in infections acquired outside the U.S. Bacterial Enteric Disease: Treatment (6) Shigella spp. May 2016www.aidsetc.org 18

 Duration of therapy  Gastroenteritis: 7-10 days (5 days for azithromycin)  Bacteremia: ≥14 days is reasonable  Recurrent infection: up to 6 weeks Bacterial Enteric Disease: Treatment (7) Shigella spp. (cont.) May 2016www.aidsetc.org 19

 Optimal treatment in HIV poorly defined  Culture and susceptibility recommended  Rates of resistance to FQs and azithromycin differ by Campylobacter species Bacterial Enteric Disease: Treatment (8) Campylobacter spp. May 2016www.aidsetc.org 20

 Mild disease and CD4 >200 copies/µL: some clinicians withhold antibiotics unless symptoms persist > several days  Mild-moderate disease (if susceptible)  Preferred  Ciprofloxacin mg PO or 400 mg IV Q12H  Azithromycin 500 mg PO QD (not recommended if bacteremia)  Alternative (depending on susceptibilities):  Levofloxacin 750 mg PO or IV Q24H  Moxifloxacin 400 mg PO or IV Q24H  Bacteremia: ciprofloxacin mg PO or 400 mg IV Q12H + aminoglycoside Bacterial Enteric Disease: Treatment (9) Campylobacter spp. May 2016www.aidsetc.org 21

 Duration of therapy  Gastroenteritis: 7-10 days (5 days for azithromycin)  Bacteremia: ≥14 days  Recurrent bacteremic disease: 2-6 weeks Bacterial Enteric Disease: Treatment (10) Campylobacter spp. (cont.) May 2016www.aidsetc.org 22

 Treatment as in HIV-uninfected patients  Vancomycin recommended over metronidazole, with possible exception of mild C difficile infection Bacterial Enteric Disease: Treatment (11) C difficile May 2016www.aidsetc.org 23

 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) Bacterial Enteric Disease: Initiating ART May 2016www.aidsetc.org 24

 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 Bacterial Enteric Disease: Monitoring and Adverse Effects May 2016www.aidsetc.org 25

 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:  Avoid coadministration of FQs with Mg- or Al-containing antacids, or with calcium, zinc, or iron (they interfere with FQ absorption  Use IV antibiotics if patient is clinically unstable Bacterial Enteric Disease: Treatment Failure May 2016www.aidsetc.org 26

 Salmonella  Consider secondary prophylaxis for patients with recurrent Salmonella bacteremia; also might consider 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  ART appears to reduce risk of recurrence  Consider stopping secondary prophylaxis if Salmonella infection is resolved, patient is on ART with viral suppression and CD4 count >200 cells/µL Bacterial Enteric Disease: Preventing Recurrence May 2016www.aidsetc.org 27

 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 Bacterial Enteric Disease: Preventing Recurrence (2) May 2016www.aidsetc.org 28

 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 (associated with increased risk of birth defects, but recent review supports use if indicated)  Sulfa therapy near delivery may increase risk to newborn of hyperbilirubinemia and kernicterus  Rifaximin can be used as with nonpregnant women Bacterial Enteric Disease: Considerations in Pregnancy May 2016www.aidsetc.org 29

  Websites to Access the Guidelines May 2016www.aidsetc.org 30

 This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in June 2013 and updated in May 2016  See the AETC NRC website for the most current version of this presentation: About This Slide Set May 2016www.aidsetc.org 31