Rifabutin-containing Regimens Research Articles

Effectiveness of Rifabutin-Based Regimens in Treating Helicobacter pylori Infections.

Helicobacter pylorihas been reported as a health problem worldwide, affecting a sizable portion of people. Peptic ulcers, gastric cancer, and various extra gastric conditions are associated with this bacterium. The rampant overprescribing of antibiotics has led to the emergence of H. pylori strains resistant to multiple antibiotics, causing a decline in the effectiveness of current treatments. Recently, there has been growing interest in researching alternative treatment options for H. pylori infections that do not respond to initial therapy. Rifabutin, a rifamycin derivative initially designed for tuberculosis treatment and preventing Mycobacterium avium complex infection, has gained attention as a potential rescue medication. It has shown efficacy against H. pylori and the potential to eradicate the bacterium when combined with other antibiotics. This systematic review article focuses on using rifabutin-based regimens as a treatment option after initial treatments have failed. The authorsscreened literature published in the last five years, between 2017 and 2022, across various search engines and closely examined relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search covered a variety of electronic databases and focused on H. pylori gastritis, rifabutin-based treatment plans, and in vivo investigations in healthy individuals. The comprehensive review provides convincing evidence that rifabutin-based regimens are effective rescue treatments for H. pylori infections. Multiple studies in various areas consistently demonstrated high eradication rates, ranging from 70% to 90%, when rifabutin-containing regimens were used. The analysis found that only a tiny percentage of H. pylori strains (1%) were resistant to rifabutin therapy, further supporting the viability of Rifabutin as an alternative when other antibiotics failed to eradicate H. pylori. The cost of Rifabutin is a significant factor that may limit its accessibility, particularly in resource-constrained settings where H. pylori infection is common.Moreover, the potential side effects of Rifabutin, such as hematological problems, rashes, and digestive issues, need to be considered. However, these side effects are typically manageable and can be reduced by combining Rifabutin with other antibiotics. In conclusion, this systematic review provides evidence supporting the effectiveness of regimens derived from Rifabutin in eliminating H. pylori infections after initial therapy failure. Due to the observation that Rifabutin effectively eradicates resistant H. pylori infections, it can be considered a suitable choice for rescue therapy. Rifabutin-containing regimens should be reserved as fourth- or later-line therapy options, considering economic factors, the risk of microbial resistance, potential side effects, and the availability of alternative medications. Future research should focus on optimizing rifabutin-based regimens and investigating combination therapies that have betterH. pylori eradication rates while also addressing the problem of resistant strains.

Tolerability Outcomes of American Thoracic Society/Infectious Diseases Society of America Guideline-Recommended Multidrug Antibiotic Treatment for Mycobacterium avium Complex Pulmonary Disease in US Medicare Beneficiaries With Bronchiectasis

Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy. Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12months of therapy initiation? In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12months of therapy initiation in various GBT regimens. The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95%CI, 1.04-1.20 with rifampin; aHR, 1.11; 95%CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95%CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95%CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95%CI, 1.43-1.64). Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD.

192. Tolerability Outcomes of Multi-drug Antibiotic Treatment for Pulmonary Nontuberculous Mycobacterial Disease due to Mycobacterium avium Complex in U.S. Medicare Beneficiaries with Bronchiectasis

BackgroundNontuberculous mycobacteria (NTM), most frequently Mycobacterium avium complex (MAC), cause increasingly common pulmonary infections. Treatment interruptions and early discontinuation are common in MAC therapy, but population-based data on treatment outcomes are severely lacking. We examined tolerability outcomes of guideline-based 3-drug therapies (GBT) targeted for pulmonary MAC infection. MethodsAmong beneficiaries with bronchiectasis (ICD-9-CM 494.0 or 494.1) in U.S. Medicare data (01/2006 – 12/2014), we identified first-time MAC GBT therapy users, excluding those with cystic fibrosis, HIV, or a history of organ transplant. MAC GBT was defined as an overlapping prescription of ≥ 28-day supply of a macrolide, ethambutol and rifamycin. Using Cox regression methods, we compared time-to-regimen change or discontinuation within 12 months of therapy start in the following groups: 1) azithromycin-ethambutol-rifamycin vs. clarithromycin-ethambutol-rifamycin; 2) macrolide-ethambutol-rifampin vs. macrolide-ethambutol-rifabutin; and 3) azithromycin-ethambutol-rifampin vs. clarithromycin-ethambutol-rifabutin.ResultsWe identified 4,626 GBT therapy users (mean 77.9 years [s.d. 6.1], female [77.7%], and non-Hispanic white [87.2%]). Overall, the rate of regimen change or discontinuation was higher in the clarithromycin-based regimens compared to azithromycin-containing regimens, and in rifabutin-containing regimens compared to rifampin-containing regimens. The rate of drug regimen change or discontinuation was 65% greater in the clarithromycin-ethambutol-rifabutin group compared to the azithromycin-ethambutol-rifampin group (adjusted hazard ratio: 1.64, 95% CI: 1.43, 1.64) (Table 1, Figure 1). ConclusionAzithromycin-based regimens and rifampin-containing regimens were less likely to be changed or discontinued within 12 months of therapy compared to clarithromycin-based regimens and rifabutin-containing regimens, respectively. More research is needed to identify factors associated with early treatment change or discontinuation. Disclosures Emily Henkle, PhD, MPH, AN2 (Consultant, Advisor or Review Panel member)Zambon (Advisor or Review Panel member) Theodore K. Marras, MD, Astra Zeneca (Speaker’s Bureau)Insmed (Scientific Research Study Investigator)Novartis (Speaker’s Bureau)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Grant/Research Support)Paratek (Consultant)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Research Grant or Support)Paratek (Consultant)RedHill Biopharma (Consultant)Spero (Consultant)

Rifabutin for the Treatment of Helicobacter Pylori Infection: A Review.

Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-to-treat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth- and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10–12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have failed.

Rifabutin for treating tuberculosis in solid organ transplant recipients: A retrospective observational study and literature review.

The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin-containing regimens were compared and a literature review was conducted. We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62years (interquartile range 50-20). There were no significant differences between patients treated with rifabutin (n=12), rifampin (n=14), and non-rifamycins (n=5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P=.21), side effects (25%, 37.5%, and 20%, respectively; P=.74), or mortality (16.7%, 35.7%, and 0%, respectively; P=.21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin-containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. Rifabutin-containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients.

Rifamycin use for treatment of Helicobacter pylori infection: a review of recent data.

Helicobacter pylori eradication has become increasingly challenging. We focused on recent data about rifamycin resistance and rifamycin-containing regimens. Rifampin (rifampicin) resistance rates were <1-18.8% (often ≤7%), while those to rifabutin were 0-<4%. To detect rifabutin resistance by rifampin, 4 mg/l breakpoint was suggested. Eradication success by rifaximin-based regimens was disappointing (<62%), while that of rifabutin-containing regimens was 54.5->96%, reaching >81% in four studies. Some newer rifamycin analogs like TNP-2092 need further investigation. Briefly, although rifabutin-based regimens carry a risk of adverse effects or increasing mycobacterial resistance, they may be a rational choice for some multidrug-resistant H. pylori strains and as a third-line eradication therapy. Bismuth addition to rifabutin-based therapy and combined rifabutin-containing capsules (Talicia) are promising treatment options.

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Review article: rifabutin in the treatment of refractory Helicobacter pylori infection

Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection. To evaluate the role of rifabutin in the treatment of H. pylori infection. Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin-containing regimens on H. pylori eradication were combined and meta-analysed using the generic inverse variance method. Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9-1.7%). When only studies including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post-treatment patients were considered. Overall, mean H. pylori eradication rate (intention-to-treat analysis) with rifabutin-containing regimens (1008 patients) was 73% (67-79%). Respective cure rates for second-line (223 patients), third-line (342 patients) and fourth/fifth-line (95 patients) rifabutin therapies were 79% (67-92%), 66% (55-77%) and 70% (60-79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10- to 12-day regimens are generally recommended. The mean rate of adverse effects was 22% (19-25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it. Rifabutin-containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin.

Treatment of Active Tuberculosis in HIV‐Coinfected Patients: A Systematic Review and Meta‐Analysis

Patients with human immunodeficiency virus (HIV) infection and tuberculosis have an increased risk of death, treatment failure, and relapse. A systematic review and meta-analysis of randomized, controlled trials and cohort studies was conducted to evaluate the impact of duration and dosing schedule of rifamycin and use of antiretroviral therapy in the treatment of active tuberculosis in HIV-positive patients. In included studies, the initial tuberculosis diagnosis, failure, and/or relapse were microbiologically confirmed, and patients received standardized rifampin- or rifabutin-containing regimens. Pooled cumulative incidence of treatment failure, death during treatment, and relapse were calculated using random-effects models. Multivariable meta-regression was performed using negative binomial regression. After screening 5158 citations, 6 randomized trials and 21 cohort studies were included. Relapse was more common with regimens using 2 months rifamycin (adjusted risk ratio, 3.6; 95% confidence interval, 1.1-11.7) than with regimens using rifamycin for at least 8 months. Compared with daily therapy in the initial phase (n=3352 patients from 35 study arms), thrice-weekly therapy (n=211 patients from 5 study arms) was associated with higher rates of failure (adjusted risk ratio, 4.0; 95% confidence interval, 1.5-10.4) and relapse [adjusted risk ratio, 4.8; 95% confidence interval, 1.8-12.8). There were trends toward higher relapse rates if rifamycins were used for only 6 months, compared with > or =8 months, or if antiretroviral therapy was not used. This review raises serious concerns regarding current recommendations for treatment of HIV-tuberculosis coinfection. The data suggest that at least 8 months duration of rifamycin therapy, initial daily dosing, and concurrent antiretroviral therapy might be associated with better outcomes, but adequately powered randomized trials are urgently needed to confirm this.

Mycobacterium tuberculosis in Solid Organ Transplant Recipients

Mycobacterium tuberculosis in Solid Organ Transplant Recipients

Where are We with current therapy?

Despite intensive research and widely publicized recommendations from consensus meetings in different continents, the public and primary care physicians are relatively slow in picking up the impact of Helicobacter pylori infection and identifying optimal therapies. The treatment of H. pylori infection has evolved from bismuth-containing regimens, 2-week proton pump inhibitor (PPI)-dual therapies, and now, the widely accepted PPI/ranitidine bismuth citrate (RBC) single week triple therapies. There is a wealth of evidence showing that these regimens are highly efficacious and well tolerated by patients. The MACH-2 studies have confirmed that the addition of a PPI to two antimicrobials has significantly improved the cure rate of H. pylori infection and reduced the impact of antimicrobial resistance. Attempts to use shorter regimens ranging from 1 to 3 days should be resisted because of their unacceptably low therapeutic efficacy. In the United States, there are some indications that 10-14 days of treatment may be required. While the first-line therapies for H. pylori infection is well established, we are still struggling with the choice of optimal regimen in retreatment after the first attempt fails. Quadruple therapy combining PPI with bismuth, metronidazole and tetracycline has achieved a respectable success of around 85%. Switching between metronidazole and clarithromycin seems to be a sensible strategy as these two are the most effective anti-Helicobacter agents. Changing between PPI and RBC in the triple therapy would not make much difference without replacing some of the antimicrobials. Rifabutin-containing regimens and high-dose PPI-amoxicillin dual therapy deserve more studies with large-scale studies. Data on anti-Helicobacter therapy for children are few. Most studies based on bismuth derivatives in combination with amoxicillin or tinidazole and were limited by the small number of cases. Recent studies showed 1-week bismuth-based triple therapy and 2-week PPI-based triple therapy are highly efficacious. Reinfection in children > 5 years of age after successful cure is rare. It is worthwhile to refine the optimal therapy for children as the treatment of this group would, theoretically, prevent the development gastric cancer in the long term.

A pilot study of antituberculosis combinations comparing rifabutin with rifampicin in the treatment of HIV-1 associated tuberculosis: A single-blind randomized evaluation in Ugandan patients with HIV-1 infection and pulmonary tuberculosis

This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic. To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB. Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide. Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated with a longer sputum conversion time for patients treated with either regimen. No major adverse events requiring dosage reduction or withdrawal of any study medication were seen in either treatment group. Mean absolute peripheral blood CD4 T lymphocyte counts increased by 28% from week 0 to week 12 in all subjects (334-427/microliters, respectively). An unexpected finding was the isolation of Mycobacterium africanum from 49% of the sputum cultures. This is the first report indicating a high prevalence of M. africanum in human TB in Uganda. Short-course antituberculosis regimens containing rifabutin or rifampicin are both safe and efficacious in the treatment of HIV-1 associated tuberculosis. Rifabutin-containing regimens were associated with earlier sputum smear and culture conversion.