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Antimicrobial Agents and Chemotherapy Sep 2023Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary disease is associated with poor treatment outcomes....
Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary disease is associated with poor treatment outcomes. In caseum surrogate, entered an extended stationary phase showing tolerance to killing by most current antibiotics, suggesting that caseum persisters contribute to the poor performance of available treatments. Novel ADP-ribosylation-resistant rifabutin analogs exhibited bactericidal activity against these persisters at concentrations achievable by rifamycins in caseum.
Topics: Humans; Rifabutin; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Anti-Bacterial Agents; Rifamycins; Microbial Sensitivity Tests
PubMed: 37493373
DOI: 10.1128/aac.00381-23 -
Antimicrobial Agents and Chemotherapy Aug 2012Lersivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) with a unique resistance profile exhibiting potent antiviral activity against wild-type HIV and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of rifampin and rifabutin on the pharmacokinetics of lersivirine and effect of lersivirine on the pharmacokinetics of rifabutin and 25-O-desacetyl-rifabutin in healthy subjects.
Lersivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) with a unique resistance profile exhibiting potent antiviral activity against wild-type HIV and several clinically relevant NNRTI-resistant strains. Lersivirine, a weak inducer of the cytochrome P450 (CYP) enzyme CYP3A4, is metabolized by CYP3A4 and UDP glucuronosyltransferase 2B7 (UGT2B7). Two open, randomized, two-way (study 1; study A5271008) or three-way (study 2; study A5271043) crossover phase I studies were carried out under steady-state conditions in healthy subjects. Study 1 (n = 17) investigated the effect of oral rifampin on the pharmacokinetics (PKs) of lersivirine. Study 2 (n = 18) investigated the effect of oral rifabutin on the PKs of lersivirine and the effect of lersivirine on the PKs of rifabutin and its active metabolite, 25-O-desacetyl-rifabutin. Coadministration with rifampin decreased the profile of the lersivirine area under the plasma concentration-time curve from time zero to 24 h postdose (AUC(24)), maximum plasma concentration (C(max)), and plasma concentration observed at 24 h postdose (C(24)) by 85% (90% confidence interval [CI], 83, 87), 83% (90% CI, 79, 85), and 92% (90% CI, 89, 94), respectively, versus the values for lersivirine alone. Coadministration with rifabutin decreased the lersivirine AUC(24), C(max), and C(24) by 34% (90% CI, 29, 39), 25% (90% CI, 16, 33), and 58% (90% CI, 52, 64), respectively, compared with the values for lersivirine alone. Neither the rifabutin concentration profile nor overall exposure was affected following coadministration with lersivirine. Lersivirine and rifabutin reduced the 25-O-desacetyl-rifabutin AUC(24) by 27% (90% CI, 21, 32) and C(max) by 27% (90% CI, 19, 34). Lersivirine should not be coadministered with rifampin, which is a potent inducer of CYP3A4, UGT2B7, and P-glycoprotein activity and thus substantially lowers lersivirine exposure. No dose adjustment of rifabutin is necessary in the presence of lersivirine; an upward dose adjustment of lersivirine may be warranted when it is coadministered with rifabutin.
Topics: Adolescent; Adult; Cross-Over Studies; Cytochrome P-450 CYP3A; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Glucuronosyltransferase; HIV; HIV Infections; Humans; Male; Middle Aged; Nitriles; Pyrazoles; Reverse Transcriptase Inhibitors; Rifabutin; Rifampin; Young Adult
PubMed: 22644026
DOI: 10.1128/AAC.06282-11 -
Antimicrobial Agents and Chemotherapy Jan 2021is a major cause of periprosthetic joint infection (PJI); its intracellular persistence within osteoblasts may compromise therapy if that therapy is not intracellularly...
is a major cause of periprosthetic joint infection (PJI); its intracellular persistence within osteoblasts may compromise therapy if that therapy is not intracellularly active. The intracellular activity of rifampin, rifapentine, and rifabutin was assessed against five rifampin-susceptible and two rifampin-resistant isolates. Compared to no treatment, treatment resulted in a ≥2-fold log reduction of intracellular rifampin-susceptible, but not rifampin-resistant, These findings show activity of rifampin, rifapentine, and rifabutin against intraosteoblast PJI-associated .
Topics: Anti-Bacterial Agents; Humans; Prosthesis-Related Infections; Rifabutin; Rifampin; Staphylococcus epidermidis
PubMed: 33199387
DOI: 10.1128/AAC.01275-20 -
The Korean Journal of Gastroenterology... Feb 2017Optimized regimen has not yet been established for failures of multiple () eradication. Hence, we aimed to evaluate the efficacy of rifabutin-based rescue therapy, at...
BACKGROUND/AIMS
Optimized regimen has not yet been established for failures of multiple () eradication. Hence, we aimed to evaluate the efficacy of rifabutin-based rescue therapy, at least after three eradication failures.
METHODS
Twelve patients, who failed in the treatment for eradication at least three times, were consecutively enrolled between 2007 and 2015 at Seoul National University Bundang Hospital. The rifabutin-based rescue regimen was consisted of proton pump inhibitor (PPI), rifabutin (150 mg b.i.d.), and amoxicillin (1 g b.i.d.), given for 7 or 14 days. MIC concentration test by the agar dilution method was performed on six patients prior to rifabutin-based rescue therapy.
RESULTS
One patient did not take this regimen, and per-protocol (PP) analysis was performed in 11 patients. The overall eradication rate by intention-to-treat and PP analysis with rifabutin-based rescue therapy was 50.0% (6/12 patients) and 54.5% (6/11 patients), respectively. There was no difference of the eradication rate depending on the underlying disease, smoking, alcohol, number of previous eradication failures, and CYP2C19 genotype. All of the six patients were susceptible to rifabutin, but only three of them succeeded in eradicating with . Side effects occurred in two patients (18.2%), and compliance was 90.9%.
CONCLUSIONS
Even the eradication rate of rifabutin-based rescue therapy was not very good. Rifabutin-based rescue therapy could be considered as a rescue therapy, perhaps as the fourth or the fifth-line treatment option. No correlation of rifabutin sensitivity with eradication success rate of suggests that frequent administration of high dose PPI and amoxicillin might be important.
Topics: Amoxicillin; Anti-Bacterial Agents; Cytochrome P-450 CYP2C19; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Proton Pump Inhibitors; Rifabutin; Treatment Failure
PubMed: 28239079
DOI: 10.4166/kjg.2017.69.2.109 -
Alimentary Pharmacology & Therapeutics Jan 2012Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection. (Review)
Review
BACKGROUND
Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection.
AIM
To evaluate the role of rifabutin in the treatment of H. pylori infection.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Rifabutin; Treatment Outcome
PubMed: 22129228
DOI: 10.1111/j.1365-2036.2011.04937.x -
The British Journal of Ophthalmology Mar 2000
Review
Topics: Antiviral Agents; Cidofovir; Cytomegalovirus Infections; Cytosine; HIV Seropositivity; Humans; Organophosphonates; Organophosphorus Compounds; Rifabutin; Sarcoidosis; Syphilis; Tuberculosis; Uveitis
PubMed: 10684829
DOI: 10.1136/bjo.84.3.233 -
Microbiology Spectrum Aug 2022Mycobacterium abscessus is an emerging human pathogen leading to significant morbidity and even mortality, intrinsically resistant to almost all the antibiotics...
Mycobacterium abscessus is an emerging human pathogen leading to significant morbidity and even mortality, intrinsically resistant to almost all the antibiotics available and so can be a nightmare. Mechanisms of its intrinsic resistance remain not fully understood. Here, we selected and confirmed an M. abscessus transposon mutant that is hypersensitive to multiple drugs including rifampin, rifabutin, vancomycin, clofazimine, linezolid, imipenem, levofloxacin, cefoxitin, and clarithromycin. The gene encoding a putative arabinosyltransferase C was found to be disrupted, using a newly developed highly-efficient strategy combining next-generation sequencing and multiple PCR. Furthermore, selectable marker-free deletion of recapitulated the hypersensitive phenotype. Disruption of resulted in an inability to synthesize lipoarabinomannan and markedly enhanced its cell envelope permeability. Complementing or M. tuberculosis restored the resistance phenotype. Importantly, treatment of M. abscessus with ethambutol, a first-line antituberculosis drug targeting arabinosyltransferases of M. tuberculosis, largely sensitized M. abscessus to multiple antibiotics . We finally tested activities of six selected drugs using a murine model of sustained M. abscessus infection and found that linezolid, rifabutin, and imipenem were active against the deletion strain. These results identified MAB_0189 as a crucial determinant of intrinsic resistance of M. abscessus, and optimizing inhibitors targeting MAB_0189 might be a strategy to disarm the intrinsic multiple antibiotic resistance of M. abscessus. Mycobacterium abscessus is intrinsically resistant to most antibiotics, and treatment of its infections is highly challenging. The mechanisms of its intrinsic resistance remain not fully understood. Here we found a transposon mutant hypersensitive to a variety of drugs and identified the transposon inserted into the (orthologous coding arabinosyltransferase, EmbC) gene by using a newly developed rapid and efficient approach. We further verified that the gene played a significant role in its intrinsic resistance by decreasing the cell envelope permeability through affecting the production of lipoarabinomannan in its cell envelope. Lastly, we found the arabinosyltransferases inhibitor, ethambutol, increased activities of nine selected drugs . Knockout of made M. abscessus become susceptible to 3 drugs in mice. These findings indicated that potential powerful M. abscessus EmbC inhibitor might be used to reverse the intrinsic resistance of M. abscessus to multiple drugs.
Topics: Animals; Anti-Bacterial Agents; Antitubercular Agents; Ethambutol; Humans; Imipenem; Linezolid; Mice; Mice, Knockout; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Pentosyltransferases; Permeability; Rifabutin; Tuberculosis
PubMed: 35946941
DOI: 10.1128/spectrum.02763-21 -
International Journal of Infectious... Dec 2017
Topics: Antibiotics, Antitubercular; Antitubercular Agents; Humans; Mycobacterium tuberculosis; Rifabutin; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 29122690
DOI: 10.1016/j.ijid.2017.10.019 -
PloS One 2013Based on drug-drug interaction, dose reduction of rifabutin is recommended when co-administered with HIV protease inhibitors for human immunodeficiency virus... (Clinical Trial)
Clinical Trial
OBJECTIVE
Based on drug-drug interaction, dose reduction of rifabutin is recommended when co-administered with HIV protease inhibitors for human immunodeficiency virus (HIV)-associated mycobacterial infection. The aim of this study was to compare the pharmacokinetics of rifabutin administered at 300 mg/day alone to that at 150 mg every other day combined with lopinavir-ritonavir in Japanese patients with HIV/mycobacterium co-infection.
METHODS
Plasma concentrations of rifabutin and its biologically active metabolite, 25-O-desacetyl rifabutin were measured in 16 cases with HIV-mycobacterial coinfection. Nine were treated with 300 mg/day rifabutin and 7 with 150 mg rifabutin every other day combined with lopinavir-ritonavir antiretroviral therapy (ART). Samples were collected at a median of 15 days (range, 5-63) of rifabutin use.
RESULTS
The mean Cmax and AUC0-24 of rifabutin in patients on rifabutin 150 mg every other day were 36% and 26% lower than on 300 mg/day rifabutin, while the mean Cmax and AUC0-24 of 25-O-desacetyl rifabutin were 186% and 152% higher, respectively. The plasma concentrations of rifabutin plus its metabolite were similar between the groups within the first 24 hours, but it remained low during subsequent 24 to 48 hours under rifabutin 150 mg alternate day dosing.
CONCLUSION
Rifabutin dose of 150 mg every other day combined with lopinavir-ritonavir seems to be associated with lower exposure to rifabutin and its metabolite compared with rifabutin 300 mg/day alone in Japanese patients. Further studies are needed to establish the optimal rifabutin dose during ART. The results highlight the importance of monitoring rifabutin plasma concentration during ART.
TRIAL REGISTRATION
UMIN-CTR (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=search&action=input&language=E) UMIN000001102.
Topics: Adult; Drug Administration Schedule; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lopinavir; Male; Middle Aged; Rifabutin; Ritonavir; Young Adult
PubMed: 23940604
DOI: 10.1371/journal.pone.0070611 -
Journal of the International AIDS... Jul 2019Rifabutin, a rifamycin of equivalent potency to rifampicin, has several advantages in its pharmacokinetic and toxicity profile, particularly in HIV co-infected patients...
INTRODUCTION
Rifabutin, a rifamycin of equivalent potency to rifampicin, has several advantages in its pharmacokinetic and toxicity profile, particularly in HIV co-infected patients on combined antiretroviral therapy (cART). In this commentary, we evaluate evidence supporting increased global use of rifabutin and highlight key recommendations for action.
DISCUSSION
Although extrapolation of data from HIV uninfected patients would suggest non-inferiority, there has been no randomized controlled study comparing rifabutin versus rifampicin in the outcomes of relapse-free cure, in drug susceptible tuberculosis (TB), in HIV co-infected patients on currently utilized cART regimens or in paediatric populations. An important advantage of rifabutin is that compared to the dose adjustments required with rifampicin, it can be co-administered with the integrase strand transfer inhibitors raltegravir or dolutegravir without the need for dose adjustments. This strategy would be easier to implement in a programmatic setting and would save costs. We have assessed cost incentives to utilize rifabutin and have estimated generic costs for a range of rifabutin dosage scenarios. Where facilities are present for drug re-challenge and monitoring for drug toxicity and cross-reactivity, rifabutin offers a switch alternative for adverse drug reactions (ADR)s attributed to rifampicin. This would negate the need to prolong treatment in the absence of a rifamycin as part of short-course multidrug therapy. There is evidence of incomplete cross-resistance to rifampicin and rifabutin. Rifabutin may be useful in rifampicin-resistant TB, in an estimated 20% of cases, based on phenotypic or genotypic rifabutin susceptibility testing.
CONCLUSIONS
Rifabutin should be available globally as a first-line rifamycin in HIV co-infected individuals and as a switch option in cases of rifampicin associated ADRs. Further studies are needed to ascertain the utility of rifabutin in rifampicin-resistant rifabutin-susceptible TB.
Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Coinfection; Drug Therapy, Combination; Female; Global Health; HIV Infections; HIV-1; Humans; Male; Rifabutin; Tuberculosis
PubMed: 31318176
DOI: 10.1002/jia2.25333