A Randomized, Double-Blind Study Comparing Single-Dose Rifalazil With Single-Dose Azithromycin for the Empirical Treatment of Nongonococcal Urethritis in Men

Stamm, Walter E.; Batteiger, Byron E.; McCormack, William M.; Totten, Patricia A.; Sternlicht, Andrew; Kivel, Nancy M.

doi:10.1097/01.olq.0000253348.44308.8c

Cited by 46 publications

(58 citation statements)

References 18 publications

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“…In considering these results, together with those obtained for C. trachomatis [24,25], it is clear that Chlamydia presents a special case in which rifalazil is not only potent against wild type bacteria, but also retains activity against mutant strains having chromosomal mutations in the rpoB gene which result in strong resistance to rifampin. The fact that rifalazil as a monotherapeutic agent was at least as effective as azithromycin, the standard of care, in the microbiological cure of C. trachomatis among men having nongonococcal urethritis in a clinical trial further supports the idea that development of resistance to rifalazil by Chlamydia is not a frequent event [14]. A total of 7 distinct rifampin-resistant mutants of C. pneumoniae, four strains having unique single mutations, and 3 strains having a unique second mutation in combination with the primary mutation at codon position 456, were isolated.…”

Section: Discussionmentioning

confidence: 83%

“…However, rifalazil was shown previously to be less prone to resistance selection when C. trachomatis was tested in cell culture, even though rifampin resistance was high [24]. The eradication of C. trachomatis among patients treated with rifalazil also suggests that resistance development among Chlamydia is not a high frequency consequence of rifalazil monotherapy [14].…”

Section: Rifalazilmentioning

confidence: 98%

“…In a Phase II clinical trial, a single 25 mg oral dose of rifalazil was shown to eradicate C. trachomatis from the majority of male patients infected with this bacterium who presented with nongonococcal urethritis [14]. More recently rifalazil has been evaluated for treatment of peripheral arterial disease, based on an association of atherosclerosis and C. pneumoniae infection, supported by animal model studies, and investigations showing the presence of C. pneumoniae in diseased vasculature [13,15].…”

Section: Rifalazilmentioning

confidence: 99%

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Rifalazil Retains Activity Against Rifampin-resistant Mutants of Chlamydia pneumoniae

et al. 2008

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Rifampin-resistant mutants of the obligate intracellular pathogen Chlamydia pneumoniae were isolated and characterized, including strains that contained multiple mutations in the rpoB gene encoding the rifampin binding site. The highest MIC of rifampin against a mutant strain exceeded 100 m g/ml, whereas the highest MIC of rifalazil was 0.125 m g/ml. Derivatives of rifalazil (new chemical entities; NCEs) showed from 2ϳ4 fold lower MICs, as well as 2ϳ8 fold lower bactericidal concentrations against both wild type and mutant strains when compared with rifalazil. These results suggest that rifalazil and NCEs are appropriate therapeutic agents for the treatment of C. pneumoniae infections from the point of view of potency and resistance development.

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Section: Discussionmentioning

confidence: 83%

Section: Rifalazilmentioning

confidence: 98%

Section: Rifalazilmentioning

confidence: 99%

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Rifalazil Retains Activity Against Rifampin-resistant Mutants of Chlamydia pneumoniae

et al. 2008

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“…This agent has been well tolerated in dose-ranging studies for the treatment of nongonococcal urethritis. 6 Because vascular infection with C pneumoniae is likely to require prolonged courses of therapy, the ability of rifalazil to promote long-term eradication of infection may be beneficial in the treatment of patients with PAD. 7 Accordingly, the goal of this study was to determine whether rifalazil would be effective in patients with symptomatic PAD.…”

Section: Clinical Perspective P 458mentioning

confidence: 99%

Anti-Chlamydial Antibiotic Therapy for Symptom Improvement in Peripheral Artery Disease

Jaff

Dale²,

Creager

et al. 2009

Circulation

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Background-A potentially strong association exists between Chlamydia pneumoniae and atherosclerosis, but the clinical benefits of antibiotic therapy have not been demonstrated. Preliminary studies of antibiotic therapy in peripheral artery disease have shown a decreased need for revascularization and improved walking ability. The objective of this phase-III trial was to assess the effect of a potent anti-Chlamydial agent, rifalazil, on peak walking time in patients with symptomatic peripheral artery disease. Methods and Results-Patients with intermittent claudication secondary to peripheral artery disease who were seropositive for C pneumoniae were randomized to 25 mg rifalazil once weekly for 8 weeks or matching placebo. Two hundred ninety-seven patients were enrolled from 3 countries and were followed up for 1 year. The meanϮSD ankle brachial index at baseline was 0.63Ϯ0.16. The primary end point, change from baseline in log peak walking time on a graded treadmill, was assessed 180 days after randomization. Secondary end points included changes in claudication onset time and quality of life, assessed with the Walking Impairment Questionnaire and the Short Form Medical Outcomes 36. No benefit of rifalazil therapy was found in the primary or any secondary end point among this cohort of patients with peripheral artery disease. The group treated with rifalazil improved their peak walking times by 23% (95% confidence interval, 15 to 31) from baseline to day 180, whereas the placebo group improved by 18% (95% confidence interval, 11 to 26; Pϭ0.38). Peak walking time, claudication onset time, Walking Impairment Questionnaire, and Short Form Medical Outcomes 36 showed no treatment-by-time interaction during the 360-day study period. Thirty-two adjudicated cardiovascular events occurred, 16 in each treatment group. Conclusions-Rifalazil did not improve exercise performance or quality of life in patients with intermittent claudication.No safety concerns were identified. Given the very small effect size, it is unlikely that larger studies would demonstrate a symptomatic benefit of this therapy in peripheral artery disease. (Circulation. 2009;119:452-458.)

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“…Rifalazil has a long elimination half-life of approximately 100 h and achieves high intracellular concentrations (11), which could reduce the likelihood of treatment failure and lessen the incidence of repeat infections. The clinical benefit of a single oral dose of 25 mg of rifalazil in treating C. trachomatis was demonstrated in a phase II clinical study which enrolled men with nongonococcal urethritis (NGU) (14). Based on data on file with the sponsor, the drug showed an acceptable tolerability profile in 486 individuals who had previously received single or multiple oral doses of rifalazil ranging from 2.5 mg to 275 mg.…”

mentioning

confidence: 99%

Randomized, Double-Blind, Multicenter Safety and Efficacy Study of Rifalazil Compared with Azithromycin for Treatment of Uncomplicated Genital Chlamydia trachomatis Infection in Women

Geisler

Pascual²,

Mathew³

et al. 2014

Antimicrob Agents Chemother

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A randomized, double-blind study comparing single-dose chlamydia therapies of oral rifalazil (25 mg) and azithromycin (1 g) was conducted in 82 women with uncomplicated genital Chlamydia trachomatis infection. The microbiologic cure rate of C. trachomatis with rifalazil (n ‫؍‬ 33) was 84.8% at the visit on day 22 to 26 (test-of-cure visit), versus 92.1% with azithromycin (n ‫؍‬ 38), and the number of treatment failures in each group was 5 and 3, respectively. The difference in cure rate was ؊7.3%, with a lower limit of the 95% confidence interval (95% CI) of ؊22.5, and thus, noninferiority was not established at the prespecified margin (lower limit of CI of ؊15%). The overall treatment-emergent adverse event (TEAE) and treatment-related TEAE rates were lower in the rifalazil group (68% and 55%) than in the azithromycin group (71% and 62%), respectively. Subjects classified as treatment failures at day 22 to 26 had a lower mean plasma concentration of rifalazil at the visit on day 8 to 12 than those classified as treatment cures, but this difference was not significant; however, the levels were similar for both groups at the visit on day 22 to 26. A single 25-mg dose of rifalazil was well tolerated and eradicated C. trachomatis in most of these women with uncomplicated genital C. trachomatis infection. (The study was registered at clinicaltrials.gov under registration no. NCT01631201).

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A Randomized, Double-Blind Study Comparing Single-Dose Rifalazil With Single-Dose Azithromycin for the Empirical Treatment of Nongonococcal Urethritis in Men

Abstract: Rifalazil was well tolerated and eradicates C. trachomatis but not M. genitalium and U. ureaplasma in men with NGU.

Cited by 46 publications

References 18 publications

Rifalazil Retains Activity Against Rifampin-resistant Mutants of Chlamydia pneumoniae

Rifalazil Retains Activity Against Rifampin-resistant Mutants of Chlamydia pneumoniae

Anti-Chlamydial Antibiotic Therapy for Symptom Improvement in Peripheral Artery Disease

Randomized, Double-Blind, Multicenter Safety and Efficacy Study of Rifalazil Compared with Azithromycin for Treatment of Uncomplicated Genital Chlamydia trachomatis Infection in Women

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