HIV Infections, Staphylococcus Aureus
Conditions
Keywords
Staphylococcus aureus, colonization, eradication, HIV, rifabutin
Brief 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.
Interventions
DRUGrifabutin plus trimethoprim sulfamethoxazole
rifabutin 300 mg PO daily or equivalent depending on concomitant medications plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days
DRUGplacebo plus trimethoprim-sulfamethoxazole
placebo plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Eradication of S. Aureus Colonization | 30 days following completion of treatment | Eradication was measured by performing cultures for S aureus at the nose, throat, and groin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eradication of S. Aureus Colonization | 7 days following completion of treatment | Eradication was measured by performing cultures for S aureus at the nose, throat, and groin |
| Recurrent Skin and Skin Structure Infections (SSTI) | up to 30 days following completion of treatment | recurrent SSTI was by self-report and exam, followed until positive colonization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rifabutin Subjects assigned to 7 days of treatment with rifabutin plus trimethoprim-sulfamethoxazole
rifabutin plus trimethoprim sulfamethoxazole: rifabutin 300 mg PO daily or equivalent depending on concomitant medications plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days | 6 |
| Placebo Subjects assigned to 7 days of treatment with placebo plus trimethoprim-sulfamethoxazole
placebo plus trimethoprim-sulfamethoxazole: placebo plus trimethoprim-sulfamethoxazole 1 DS tab twice daily both for 7 days | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Rifabutin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.3 years | 43.5 years | 42.9 years |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Eradication of S. Aureus Colonization
Eradication was measured by performing cultures for S aureus at the nose, throat, and groin
Time frame: 30 days following completion of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rifabutin | Eradication of S. Aureus Colonization | 0 participants |
| Placebo | Eradication of S. Aureus Colonization | 0 participants |
Secondary
Eradication of S. Aureus Colonization
Eradication was measured by performing cultures for S aureus at the nose, throat, and groin
Time frame: 7 days following completion of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rifabutin | Eradication of S. Aureus Colonization | 3 participants |
| Placebo | Eradication of S. Aureus Colonization | 1 participants |
Secondary
Eradication of S. Aureus Colonization
Eradication was measured by performing cultures for S aureus at the nose, throat, and groin
Time frame: 60 days following completion of treatment
Population: Participants were colonized at day 30 (i.e. S. Aureus not eradicated) and were not checked again for follow-up.
Secondary
Recurrent Skin and Skin Structure Infections (SSTI)
recurrent SSTI was by self-report and exam, followed until positive colonization
Time frame: up to 30 days following completion of treatment
Population: participants were followed until colonization; therefore, no participants were followed past 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rifabutin | Recurrent Skin and Skin Structure Infections (SSTI) | 0 participants |
| Placebo | Recurrent Skin and Skin Structure Infections (SSTI) | 0 participants |