Rifabutin Based Therapy for the Eradication of Staphylococcus Aureus Colonization in HIV Infected Adults
Condition: Staphylococcus Aureus; HIV Infections
MeSH terms: Infections; Staphylococcal Infections
Intervention: rifabutin plus trimethoprim sulfamethoxazole; placebo plus trimethoprim-sulfamethoxazole
Intervention description: rifabutin 300 mg PO daily or equivalent depending on concomitant medications plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days; placebo plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days
Intervention MeSH terms: Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Sulfamethoxazole; Rifabutin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Staphylococcus aureus; colonization; eradication; HIV; rifabutin

Summary:

      DESIGN: This single center, double-blinded, randomized phase II study is being conducted to
      assess the efficacy of a rifabutin based regimen to eliminate S. aureus colonization in HIV
      infected individuals. Individuals must have HIV infection and a skin and skin structure
      infection (SSSI) in the prior 6 months to be eligible for screening. Prior to enrollment,
      subjects will be cultured for evidence of S. aureus colonization. Individuals who are culture
      positive at ≥ one body site will be eligible for enrollment. Subjects who meet inclusion and
      exclusion criteria and consent to participate in the study will be randomized to seven days
      of rifabutin plus trimethoprim-sulfamethoxazole (TMP-SMX) or TMP-SMX alone. Following
      completion of treatment subjects will be screened seven days, 30 days, and 60 days
      post-treatment for colonization at multiple body-sites. Subjects will also be actively
      followed for evidence of SSSI.

      SUBJECT PARTICIPATION DURATION: 12 weeks

      SAMPLE SIZE: 88 total subjects

      POPULATION: 200 HIV infected individuals who receive care at San Francisco General Hospital
      HIV clinic (Ward 86) with a history of SSSI in the prior 6 months will be screened for S.
      aureus colonization.

      DESCRIPTION OF AGENT OR INTERVENTION: This is a double-blind trial comparing rifabutin plus
      TMP-SMX versus placebo plus TMP-SMX. Placebo will be administered at a dose of 300 mg p.o.
      daily or an equivalent dose depending on co-administration of other drugs that may adjust the
      serum level of rifabutin. TMP-SMX will be administered at a dose of trimethoprim 160 mg and
      sulfamethoxazole 800 mg p.o. twice daily or adjusted per CrCl. Study drug will be provided by
      the study and administered for 7 days.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age > 18 years

          2. HIV infection as reported by the subject's physician

          3. Physician-reported SSSI within the prior 6 months.

          4. S. aureus colonization at ≥ 1 body site as defined as a positive culture for S. aureus
             at minimum one of five cultures taken at pre-enrollment screening.

          5. Subjects (or their legally acceptable representatives) must have signed an informed
             consent documentation indicating that they understand the purpose of and procedures
             required for the study, and are willing to participate in the study

        Exclusion Criteria:

          1. Female subjects who are pregnant or lactating.

          2. Known or suspected hypersensitivity to rifabutin, a rifamycin class antimicrobial,
             TMP-SMX or another sulfa based medication.

          3. Known or suspected condition or concurrent treatment that would be contraindicated by
             the prescribing of rifabutin or TMP-SMX.

          4. Receipt of an anti-staphylococcal antimicrobial within 14 days prior to administration
             of study drug (TMP-SMX, clindamycin, any macrolide, any tetracycline, any rifamycin,
             any fluoroquinolone, vancomycin, linezolid, daptomycin, any penicillin, any
             carbapenem, or any cephalosporin).

          5. Diagnosis of an active SSSI or other signs and symptoms of S. aureus infection at the
             time of study enrollment

          6. Physician-reported diagnosis of active or untreated latent mycobacterial infection

          7. CrCl < 30 ml/min as determined by the Cockcroft-Gault Method using a serum creatinine
             from a value obtained within the last 6 months.

          8. No serum creatinine value available for the subject in the SFGH clinical laboratory
             system (LCR) within 6 months prior to enrollment.

          9. Physician-reported diagnosis of end-stage liver disease

         10. Physician-reported diagnosis of uveitis in the past or at time of enrollment

         11. Concomitant use of medications with unknown pharmacokinetic interactions with
             rifabutin or contraindicated with rifabutin (unboosted indinavir, unboosted
             saquinavir, delavirdine, atovaquone, azithromycin, Bacillus of Calmette and Guerin
             [only if recent administration for bladder cancer treatment], dapsone, dasatinib,
             erlotininb, ethinyl estradiol, fluconazole, imatinab, itinotecan, itraconazole,
             ixabepilone, lapatinib, levonorgestrel, mestranol, nilotininb, norelgestromin,
             norethindrone, posaconazole, ranolazine, sirolimus, sunitinib, tacrolimus,
             temsirolimus, trimetrexate, voriconazole, warfarin)

         12. Colonizing S. aureus isolate resistant to TMP-SMX

         13. Colonizing S. aureus isolate resistant to rifampin (rifampin resistance will serve as
             a surrogate for rifabutin resistance at initial screening)

         14. Subjects who are unlikely to be able to comply with the mandated study visits