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The Journal of Antimicrobial... Jul 2016Rifabutin is a spiro-piperidyl-rifamycin structurally closely related to rifampicin that shares many of its properties. We attempted to address the reasons why this... (Review)
Review
Rifabutin is a spiro-piperidyl-rifamycin structurally closely related to rifampicin that shares many of its properties. We attempted to address the reasons why this drug, which was recently recognized as a WHO Essential Medicine, still had a far narrower range of indications than rifampicin, 24 years after its launch. In this comprehensive review of the classic and more recent rifabutin experimental and clinical studies, the current state of knowledge about rifabutin is depicted, relying on specific pharmacokinetics, pharmacodynamics, antimicrobial properties, resistance data and side effects compared with rifampicin. There are consistent in vitro data and clinical studies showing that rifabutin has at least equivalent activity/efficacy and acceptable tolerance compared with rifampicin in TB and non-tuberculous mycobacterial diseases. Clinical studies have emphasized the clinical benefits of low rifabutin liver induction in patients with AIDS under PIs, in solid organ transplant patients under immunosuppressive drugs or in patients presenting intolerable side effects related to rifampicin. The contribution of rifabutin for rifampicin-resistant, but rifabutin-susceptible, Mycobacterium tuberculosis isolates according to the present breakpoints has been challenged and is now controversial. Compared with rifampicin, rifabutin's lower AUC is balanced by higher intracellular penetration and lower MIC for most pathogens. Clinical studies are lacking in non-mycobacterial infections.
Topics: Antibiotics, Antitubercular; Clinical Trials as Topic; Humans; Microbial Sensitivity Tests; Mycobacterium Infections; Mycobacterium tuberculosis; Rifabutin; Rifampin
PubMed: 27009031
DOI: 10.1093/jac/dkw024 -
The Annals of Pharmacotherapy Nov 1995To review rifabutin-associated uveitis and discuss the mechanism and potential role of drug interactions with clarithromycin and fluconazole in contributing to this... (Comparative Study)
Comparative Study Review
OBJECTIVE
To review rifabutin-associated uveitis and discuss the mechanism and potential role of drug interactions with clarithromycin and fluconazole in contributing to this adverse event.
DATA SOURCES
A MEDLINE search (1991 through September 1994) of English-language literature using the main MeSH headings "rifabutin" and "uveitis" and the subheadings "adverse effects" and "chemically induced." Relevant articles also were selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology, and HIV were screened for additional data.
STUDY SELECTION AND DATA EXTRACTION
All articles and abstracts reporting uveitis potentially related to rifabutin were considered for inclusion. Fifty-four cases were identified. Pertinent information from the case reports, as judged by the authors, was selected and synthesized for discussion.
DATA SYNTHESIS
Rifabutin is being prescribed increasingly for the treatment and prophylaxis of Mycobacterium avium complex (MAC) infection in the HIV-infected population. Uveitis was initially thought to be a rare, dose-limited complication of rifabutin therapy. In an early dose-ranging tolerance study, uveitis was associated with daily doses of 1200 mg or more. Because this toxicity appeared to be dose-related, lower dosages (300-600 mg/d) of rifabutin were selected for study in subsequent clinical trials. More recent reports noting the association of uveitis with these lower dosages of rifabutin have raised concerns about the prevalence of this adverse event. In the 54 identified cases, patients presented with symptoms of unilateral or bilateral uveitis from 2 weeks to more than 7 months following initiation of rifabutin therapy. In all reported cases, patients were receiving concurrent therapy with clarithromycin and/or fluconazole, both of which have inhibitory effects on rifabutin metabolism. In most cases, uveitis resolved within 1-2 months following discontinuation of rifabutin with or without administration of topical corticosteroids.
CONCLUSIONS
Rifabutin is prescribed frequently for the prophylaxis and treatment of MAC infection, especially in patients with HIV. Uveitis is a rare, dose-related toxicity of this therapy. The risk of rifabutin-associated uveitis may be increased in patients receiving concurrent therapy with clarithromycin or fluconazole because of drug interactions. Patients receiving therapy with combinations of any of these agents should be warned about signs and symptoms of uveitis and be monitored closely for the development of rifabutin toxicity. If uveitis develops, rifabutin therapy should be discontinued promptly.
Topics: Anti-Bacterial Agents; Antifungal Agents; Clarithromycin; Clinical Trials as Topic; Drug Interactions; Fluconazole; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Uveitis
PubMed: 8573961
DOI: 10.1177/106002809502901114 -
Tuberculosis (Edinburgh, Scotland) Mar 2008
Review
Topics: Animals; Antibiotics, Antitubercular; Humans; Rifabutin; Treatment Outcome; Tuberculosis
PubMed: 18486056
DOI: 10.1016/S1472-9792(08)70022-2 -
Drug Discovery Today Sep 2021Rifamycin antibiotics were discovered during the 1950s, and their main representative, rifampicin, remains a cornerstone treatment for TB. The clinical use of rifamycin... (Review)
Review
Rifamycin antibiotics were discovered during the 1950s, and their main representative, rifampicin, remains a cornerstone treatment for TB. The clinical use of rifamycin is restricted to mycobacteria and Gram-positive infections because of its poor ability to penetrate the Gram-negative outer membrane. Rifabutin, a rifamycin antibiotic approved for the prevention of Mycobacterium avium complex disease, makes an exception to this rule by hijacking the iron uptake system of Acinetobacter baumannii, resulting in potent activity against this important Gram-negative pathogen. Here, we describe recent findings on the specific activity of rifabutin and provide evidence of the need for the development of an intravenous formulation of rifabutin (BV100) for the treatment of difficult-to-treat carbapenem-resistant A.baumannii infections.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Humans; Infusions, Intravenous; Rifabutin
PubMed: 34242796
DOI: 10.1016/j.drudis.2021.07.001 -
The Cochrane Database of Systematic... Oct 2007Rifamycins are an essential component of modern short-course regimens for treating tuberculosis. Rifabutin has favourable pharmacokinetic and pharmacodynamic properties... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rifamycins are an essential component of modern short-course regimens for treating tuberculosis. Rifabutin has favourable pharmacokinetic and pharmacodynamic properties and is less prone to drug-drug interactions than rifampicin. It could contribute to shortening of therapy or simplify treatment in HIV-positive people who also need antiretroviral drugs.
OBJECTIVES
To compare combination drug regimens containing rifabutin with those containing rifampicin for treating pulmonary tuberculosis
SEARCH STRATEGY
We searched Cochrane Infectious Diseases Group Specialized Register (January 2007), CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE (1966 to January 2007), EMBASE (1974 to January 2007), and LILACS (1982 to January 2007). We also searched the Indian Journal of Tuberculosis (1983 to 2006), conference abstracts, reference lists, and unpublished data on file at Pfizer Inc.
SELECTION CRITERIA
Randomized and quasi-randomized trials including participants with sputum smear and/or culture-confirmed tuberculosis that compared a rifabutin-containing with an otherwise identical rifampicin-containing regimen.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study eligibility and methodological quality, and extracted data. Dichotomous data were analysed and combined using relative risks (RR) with 95% confidence intervals (CI) using a fixed-effect model. Subgroup analyses were carried out according to rifabutin dose.
MAIN RESULTS
Five trials with a total of 924 participants met the inclusion criteria; 5% of participants were HIV positive. Only one small trial was methodologically adequate. The two largest trials (818 participants) had unclear allocation concealment and included < 90% of randomized participants in the analysis. There was no statistically significant difference in between the regimens for cure (RR 1.00, 95% CI 0.96 to 1.04; 553 participants, 2 trials) or relapse (RR 1.23, 95% CI 0.45 to 3.35; 448 participants, 2 trials). The number of adverse events was not significantly different (RR 1.42, 95% CI 0.88 to 2.31; 714 participants, 3 trials), though the RR increased with rifabutin dose: 150 mg (RR 0.98, 95% CI 0.45 to 2.12; 264 participants, 2 trials); and 300 mg (RR 1.78, 95% CI 0.94 to 3.34; 450 participants, 2 trials). However, lack of dose adjustment by weight in the relevant trials complicates interpretation of this relationship.
AUTHORS' CONCLUSIONS
The replacement of rifampicin by rifabutin for first-line treatment of tuberculosis is not supported by the current evidence. HIV-positive people with tuberculosis, the group most likely to benefit from the rifabutin use, are under-represented in trials to date, and further trials in this group would be useful.
Topics: Antibiotics, Antitubercular; Humans; Randomized Controlled Trials as Topic; Rifabutin; Rifampin; Tuberculosis, Pulmonary; Uveitis
PubMed: 17943842
DOI: 10.1002/14651858.CD005159.pub2 -
Antimicrobial Agents and Chemotherapy Feb 2021exhibits Arr (ADP-ribosyltransferase)-dependent rifampin resistance. In apparent contrast, rifabutin (RBT) has demonstrated promising activity in infection models,...
exhibits Arr (ADP-ribosyltransferase)-dependent rifampin resistance. In apparent contrast, rifabutin (RBT) has demonstrated promising activity in infection models, implying that RBT might not be inactivated by Arr. RBT susceptibility testing of revealed a strongly decreased MIC. Our findings suggest that the efficacy of RBT might be enhanced by rendering RBT resilient to Arr-dependent modification or by blocking Arr activity.
Topics: ADP Ribose Transferases; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Rifabutin; Rifampin
PubMed: 33318008
DOI: 10.1128/AAC.02215-20 -
Clinical Pharmacokinetics Feb 1995The clinical effectiveness of rifabutin for prophylaxis of disseminated Mycobacterium avium complex infection has recently been demonstrated in HIV-positive patients... (Review)
Review
The clinical effectiveness of rifabutin for prophylaxis of disseminated Mycobacterium avium complex infection has recently been demonstrated in HIV-positive patients with low CD4 counts. Rifabutin is a newly marketed, semisynthetic antimycobacterial agent similar to rifampicin (rifampin) in structure and activity. However, rifabutin has important pharmacokinetic differences compared with rifampicin. Rifabutin has relatively low oral bioavailability; about 20% after single dose administration. With long term administration rifabutin induces its own metabolism and the metabolism of some other drugs. The elimination half-life of rifabutin is long (45 hours) but, as a result of a very large volume of distribution (> 9 L/kg), average plasma concentrations remain relatively low after repeated administration of standard doses. In vitro rifabutin is more active against M. avium-intracellulare complex and at least as active against M. tuberculosis as rifampicin. In vivo the advantage of rifabutin is less apparent due to its lower plasma concentrations at equivalent doses. Adverse effects are unusual at the recommended oral dosage of 300 mg/day, but become common as the total daily dose approaches 1 g. Dose-limiting toxicity consists of a polyarthralgia/arthritis syndrome, possibly complicated by uveitis. More clinical studies are needed to establish the role of rifabutin in combination therapy for M. avium-intracellulare complex and other mycobacterial infections.
Topics: Absorption; Aging; Drug Interactions; Drug Tolerance; HIV Infections; Half-Life; Humans; Liver Diseases; Mycobacterium Infections; Protein Binding; Rifabutin; Tissue Distribution
PubMed: 7736687
DOI: 10.2165/00003088-199528020-00003 -
The Pediatric Infectious Disease Journal Jan 1998
Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin
PubMed: 9469400
DOI: 10.1097/00006454-199801000-00016 -
Drugs Jun 1994Rifabutin is a derivative of rifamycin S with activity against mycobacteria including atypical organisms such as Mycobacterium avium and M. intracellulare, also referred... (Review)
Review
Rifabutin is a derivative of rifamycin S with activity against mycobacteria including atypical organisms such as Mycobacterium avium and M. intracellulare, also referred to as Mycobacterium avium-intracellulare complex (MAC). To date, rifabutin is the only drug to have been studied in large prospective placebo-controlled trials that has been shown to significantly reduce the incidence of disseminated MAC infection when administered prophylactically as a single agent to patients with acquired immune deficiency syndrome (AIDS). Initial studies also indicate that rifabutin may be a useful component of multiple drug regimens for the treatment of MAC infection, although further studies combining rifabutin with other recently available antimycobacterial drugs are required to determine the most effective regimens. When rifabutin is combined with at least two other antimycobacterial drugs, the combination appears to be of similar efficacy to rifampicin (rifampin)-containing regimens in patients with newly diagnosed pulmonary tuberculosis. Since available therapy for MAC infection in patients with AIDS is still suboptimal, rifabutin, at present the only first-line agent for prophylaxis against disseminated MAC infection in patients with advanced human immunodeficiency virus (HIV) infection, has the potential to make a valuable contribution to the continuing attempts to preserve the quality of life of patients with AIDS.
Topics: AIDS-Related Opportunistic Infections; Animals; Bacteria; Biological Availability; Drug Interactions; Half-Life; Humans; Intestinal Absorption; Metabolic Clearance Rate; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Tissue Distribution; Tuberculosis, Pulmonary
PubMed: 7521834
DOI: 10.2165/00003495-199447060-00008 -
Antimicrobial Agents and Chemotherapy Jan 2020There is no reliable cure for lung disease. Rifampin is not used clinically due to poor potency. In contrast, we have shown that rifabutin, another approved rifamycin...
There is no reliable cure for lung disease. Rifampin is not used clinically due to poor potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent against Here, we report that rifabutin is as active as clarithromycin against K21 in NOD.CB17-Prkdc/NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with disease.
Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Disease Models, Animal; Drug Repositioning; Female; Humans; Lung Diseases; Mice; Mice, Inbred NOD; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Rifabutin
PubMed: 31767722
DOI: 10.1128/AAC.01943-19