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Journal of the International... 2013Drug-induced lupus (DIL) is a rare adverse reaction to medications with features resembling idiopathic systemic lupus erythromatosis. Rifabutin/rifamycins have only... (Review)
Review
Drug-induced lupus (DIL) is a rare adverse reaction to medications with features resembling idiopathic systemic lupus erythromatosis. Rifabutin/rifamycins have only rarely been reported as a cause of DIL, and no cases have been reported in blacks. A 55-year-old African American woman with HIV presented with severe generalized arthralgias and recurrent oral ulcers while receiving treatment for tuberculous meningitis. Arthralgias, which began in her knees after 5 weeks of antituberculous therapy, progressed to involve the joints in the ankles, wrists, and hands. She had no associated fever or rash. When she had these symptoms her antinuclear antibody (ANA) was 1:1280 homogenous pattern, antidouble stranded DNA was negative, antihistone antibody was strongly positive, anti-smith and antiribonucleoprotein (anti-RNP) were negative. Her symptoms resolved within 2 months of stopping rifabutin while continuing other antituberculous medications and her ANA titer started to decrease. We review the existing literature on this subject.
Topics: Antibiotics, Antitubercular; Female; HIV Infections; Humans; Lupus Erythematosus, Systemic; Middle Aged; Rifabutin; Tuberculosis
PubMed: 23442494
DOI: 10.1177/2325957412473647 -
Antimicrobial Resistance and Infection... 2019Nepal and Bangladesh have a high prevalence of with high resistance rates to clarithromycin, metronidazole, and levofloxacin. Here, we evaluated the susceptibility and...
BACKGROUND
Nepal and Bangladesh have a high prevalence of with high resistance rates to clarithromycin, metronidazole, and levofloxacin. Here, we evaluated the susceptibility and genetic mutations of 5 alternative antibiotics against isolates from both countries to obtain an effective treatment regimen for eradication.
METHODS
We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics against 42 strains from Nepal and 56 from Bangladesh and performed whole genome mutation analysis.
RESULTS
No resistance to furazolidone or rifabutin and a high susceptibility of sitafloxacin (95.2% in Nepal and 98.2% in Bangladesh) were observed. In contrast, resistance to rifaximin (52.4% in Nepal and 64.3% in Bangladesh) was high. Moreover, resistance to garenoxacin was higher in Bangladesh (51.6%) than in Nepal (28.6%, = 0.041), most likely due to its correlation with levofloxacin resistance ( = 0.03). Garenoxacin and rifaximin were significantly correlated in Bangladesh ( = 0.014) and occurred together with all sitafloxacin-resistant strains. Mutations of could play a significant role in garenoxacin resistance, and double mutations of A87 and D91 were associated with sitafloxacin resistance. Analysis of the gene demonstrated well-known mutations, such as V657I, and several novel mutations, including I2619V, V2592 L, T2537A, and F2538 L.
CONCLUSIONS
Rifabutin can be cautiously implemented as therapy for infection due to its interaction with the tuberculosis endemic in Bangladesh. The high susceptibility of furazolidone and sitafloxacin suggests their possible future application in Nepal and Bangladesh.
Topics: Anti-Bacterial Agents; Bangladesh; DNA Gyrase; DNA, Bacterial; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Female; Fluoroquinolones; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Mutation; Nepal; Rifabutin; Whole Genome Sequencing
PubMed: 30815255
DOI: 10.1186/s13756-019-0482-x -
Alimentary Pharmacology & Therapeutics Jul 2006The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin.
BACKGROUND
The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge.
AIM
To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome.
METHODS
Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism.
RESULTS
Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers.
CONCLUSIONS
Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.
Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Cross-Over Studies; Drug Resistance, Bacterial; Drug Therapy, Combination; Esomeprazole; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Prospective Studies; Rifabutin; Treatment Outcome
PubMed: 16842467
DOI: 10.1111/j.1365-2036.2006.02993.x -
Drug and Alcohol Dependence Nov 2011This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of...
BACKGROUND
This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication.
METHODS
Opioid-dependent individuals on stable doses of buprenorphine/naloxone underwent two, 24-h blood sampling studies: (1) for buprenorphine pharmacokinetics and (2) following 15 days of rifampin 600 mg daily or rifabutin 300 mg daily for buprenorphine and rifampin or rifabutin pharmacokinetics.
RESULTS
Rifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0.001) and onset of opiate withdrawal symptoms in 50% of participants (p=0.02). While rifabutin administration to buprenorphine-maintained subjects resulted in a significant decrease in buprenorphine plasma concentrations (35% decrease in AUC; p<0.001) no opiate withdrawal was seen. Compared with historical control data, buprenorphine had no significant effect on rifampin pharmacokinetics, but was associated with 22% lower rifabutin mean AUC (p=0.009), although rifabutin and its active metabolite concentrations remained in the therapeutic range.
CONCLUSIONS
Rifampin is a more potent inducer of buprenorphine metabolism than rifabutin with pharmacokinetic and pharmacodynamic adverse consequences. Those patients requiring rifampin treatment for tuberculosis and receiving buprenorphine therapy are likely to require an increase in buprenorphine dose to prevent withdrawal symptoms. Rifabutin administration was associated with decreases in buprenorphine plasma concentrations, but no clinically significant adverse events were observed.
Topics: Adult; Antitubercular Agents; Buprenorphine; Drug Interactions; Female; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Rifabutin; Rifampin; Substance Withdrawal Syndrome
PubMed: 21596492
DOI: 10.1016/j.drugalcdep.2011.04.013 -
Chest May 2021A Phase I, single-center investigation found that 8 weeks of antimycobacterial therapy improved sarcoidosis FVC. Safety and efficacy assessments have not been performed... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
A Phase I, single-center investigation found that 8 weeks of antimycobacterial therapy improved sarcoidosis FVC. Safety and efficacy assessments have not been performed in a multicenter cohort.
RESEARCH QUESTION
The objective of this study was to determine the safety and efficacy of antimycobacterial therapy on the physiological and immunologic end points of sarcoidosis.
STUDY DESIGN AND METHODS
In a double-blind, placebo-controlled, multicenter investigation, patients with pulmonary sarcoidosis were randomly assigned to receive 16 weeks of concomitant levofloxacin, ethambutol, azithromycin, and rifabutin (CLEAR) or matching placebo to investigate the effect on FVC. The primary outcome was a comparison of change in percentage of predicted FVC among patients randomized to receive CLEAR or placebo in addition to their baseline immunosuppressive regimen. Secondary outcomes included 6-min walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) score, adverse events, and decrease in mycobacterial early secreted antigenic target of 6 kDa (ESAT-6) immune responses.
RESULTS
The intention-to-treat analysis revealed no significant differences in change in FVC among the 49 patients randomized to receive CLEAR (1.1% decrease) compared with the 48 randomized to receive placebo (0.02% increase) (P = .64). Physiological parameters such as the change in 6MWD were likewise similar (P = .91); change in SGRQ favored placebo (-8.0 for placebo vs -1.5 for CLEAR; P = .028). The per-protocol analysis revealed no significant change in FVC at 16 weeks between CLEAR and placebo. There was no significant change in 6MWD (36.4 m vs 6.3 m; P = .24) or SGRQ (-2.3 vs -7.0; P = .14). A decline in ESAT-6 immune responses at 16 weeks was noted among CLEAR-treated patients (P = .0003) but not patients receiving placebo (P = .24).
INTERPRETATION
Despite a significant decline in ESAT-6 immune responses, a 16-week CLEAR regimen provided no physiological benefit in FVC or 6MWD among patients with sarcoidosis.
Topics: Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Ethambutol; Female; Humans; Levofloxacin; Male; Middle Aged; Respiratory Function Tests; Rifabutin; Sarcoidosis, Pulmonary
PubMed: 33387486
DOI: 10.1016/j.chest.2020.12.027 -
The Cochrane Database of Systematic... Jul 2013Preventing active tuberculosis (TB) from developing in people with latent tuberculosis infection (LTBI) is important for global TB control. Isoniazid (INH) for six to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preventing active tuberculosis (TB) from developing in people with latent tuberculosis infection (LTBI) is important for global TB control. Isoniazid (INH) for six to nine months has 60% to 90% protective efficacy, but the treatment period is long, liver toxicity is a problem, and completion rates outside trials are only around 50%. Rifampicin or rifamycin-combination treatments are shorter and may result in higher completion rates.
OBJECTIVES
To compare the effects of rifampicin monotherapy or rifamycin-combination therapy versus INH monotherapy for preventing active TB in HIV-negative people at risk of developing active TB.
SEARCH METHODS
We searched the Cochrane Infectious Disease Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; clinical trials registries; regional databases; conference proceedings; and references, without language restrictions to December 2012; and contacted experts for relevant published, unpublished and ongoing trials.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of HIV-negative adults and children at risk of active TB treated with rifampicin, or rifamycin-combination therapy with or without INH (any dose or duration), compared with INH for six to nine months.
DATA COLLECTION AND ANALYSIS
At least two authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. We pooled relative risks (RRs) with their 95% confidence intervals (CIs), using a random-effects model if heterogeneity was significant. We assessed overall evidence quality using the GRADE approach.
MAIN RESULTS
Ten trials are included, enrolling 10,717 adults and children, mostly HIV-negative (2% HIV-positive), with a follow-up period ranging from two to five years. Rifampicin (three/four months) vs. INH (six months)Five trials published between 1992 to 2012 compared these regimens, and one small 1992 trial in adults with silicosis did not detect a difference in the occurrence of TB over five years of follow up (one trial, 312 participants; very low quality evidence). However, more people in these trials completed the shorter course (RR 1.19, 95% CI 1.01 to 1.30; five trials, 1768 participants; moderate quality evidence). Treatment-limiting adverse events were not significantly different (four trials, 1674 participants; very low quality evidence), but rifampicin caused less hepatotoxicity (RR 0.12, 95% CI 0.05 to 0.30; four trials, 1674 participants; moderate quality evidence). Rifampicin plus INH (three months) vs. INH (six months)The 1992 silicosis trial did not detect a difference between people receiving rifampicin plus INH compared to INH alone for occurrence of active TB (one trial, 328 participants; very low quality evidence). Adherence was similar in this and a 1998 trial in people without silicosis (two trials, 524 participants; high quality evidence). No difference was detected for treatment-limiting adverse events (two trials, 536 participants; low quality evidence), or hepatotoxicity (two trials, 536 participants; low quality evidence). Rifampicin plus pyrazinamide (two months) vs. INH (six months)Three small trials published in 1994, 2003, and 2005 compared these two regimens, and two reported a low occurrence of active TB, with no statistically significant differences between treatment regimens (two trials, 176 participants; very low quality evidence) though, apart from one child from the 1994 trial, these data on active TB were from the 2003 trial in adults with silicosis. Adherence with both regimens was low with no statistically significant differences (four trials, 700 participants; very low quality evidence). However, people receiving rifampicin plus pyrazinamide had more treatment-limiting adverse events (RR 3.61, 95% CI 1.82 to 7.19; two trials, 368 participants; high quality evidence), and hepatotoxicity (RR 4.59, 95% 2.14 to 9.85; three trials, 540 participants; moderate quality evidence). Weekly, directly-observed rifapentine plus INH (three months) vs. daily, self-administered INH (nine months)A large trial conducted from 2001 to 2008 among close contacts of TB in the USA, Canada, Brazil and Spain found directly observed weekly treatment to be non-inferior to nine months self-administered INH for the incidence of active TB (0.2% vs 0.4%, RR 0.44, 95% CI 0.18 to 1.07, one trial, 7731 participants; moderate quality evidence). The directly-observed, shorter regimen had higher treatment completion (82% vs 69%, RR 1.19, 95% CI 1.16 to 1.22, moderate quality evidence), and less hepatotoxicity (0.4% versus 2.4%; RR 0.16, 95% CI 0.10 to 0.27; high quality evidence), though treatment-limiting adverse events were more frequent (4.9% versus 3.7%; RR 1.32, 95% CI 1.07 to 1.64 moderate quality evidence)
AUTHORS' CONCLUSIONS
Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH. Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens. Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens. Rifampicin combined with pyrazinamide is associated with more adverse events. A weekly regimen of rifapentine plus INH has higher completion rates, and less liver toxicity, though treatment discontinuation due to adverse events is probably more likely than with INH.
Topics: Adult; Antibiotics, Antitubercular; Child; Directly Observed Therapy; Drug Administration Schedule; HIV Seronegativity; Humans; Isoniazid; Latent Tuberculosis; Randomized Controlled Trials as Topic; Rifabutin; Rifampin; Tuberculosis, Pulmonary
PubMed: 23828580
DOI: 10.1002/14651858.CD007545.pub2 -
Gastroenterologie Clinique Et Biologique Mar 2003Helicobacter pylori eradication failure generally concerns between 10 and 30% of the patients. When eradication failure occurs, it is necessary a) to try to identify the... (Review)
Review
Helicobacter pylori eradication failure generally concerns between 10 and 30% of the patients. When eradication failure occurs, it is necessary a) to try to identify the potential causes, b) to confirm the indication of eradicating H. pylori, and c) to choose a second line therapeutic strategy. Among the factors most frequently associated with failed eradication, are poor compliance, younger age, smoking, and weak gastric inflammatory activity. The major factor of resistance is related to the sensitivity of the bacterial strain to antibiotics used. In France, resistance to clarithromycin is around 10-15% and resistance to metronidazole around 30%. In order to limit development of resistance, it seems preferable to avoid associating clarithromycin and metronidazole in the first line treatment. At best, the first line treatment must follow the official recommendations (PPI-amoxicillin and clarithromycin). In the event of eradication failure, second line treatment calls upon tritherapy which, due to the low rate of resistance to amoxicillin, associates double-dose PPI, amoxicillin and the antibiotic not used during the first line treatment (metronidazole if clarithromycin was initially used and conversely). This approach allows to eradicate between 50 and 80% of the first-line failure patients. In case of further failure a culture with measurement of the strain sensitivity is required. Subsequent treatment associates PPI with the antibiotics to which the strain is sensitive for a longer duration. In some cases, other effective antibiotics, such as rifabutin, might be used in these circumstances.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Penicillins; Recurrence; Rifabutin
PubMed: 12700506
DOI: No ID Found -
Biochemical Pharmacology Apr 2012Quinones represent a large and diverse class of antitumor drugs and many quinones are approved for clinical use or are currently undergoing evaluation in clinical... (Review)
Review
Quinones represent a large and diverse class of antitumor drugs and many quinones are approved for clinical use or are currently undergoing evaluation in clinical trials. For many quinones reduction to the hydroquinone has been shown to play a key role in their antitumor activity. The two-electron reduction of quinones by NQO1 has been shown to be an efficient pathway to hydroquinone formation. NQO1 is expressed at high levels in many human solid tumors making this enzyme ideally suited for intracellular drug activation. Cellular levels of NQO1 are influenced by the NQO1*2 polymorphism. Individuals homozygous for the NQO1*2 allele are NQO1 null and homozygous NQO1*2*2 cell lines have been shown to be more resistant to antitumor quinones when compared to isogenic cell lines overexpressing NQO1. In this review we will discuss the role of NQO1 in the sensitivity and resistance of human cancers to the quinone antitumor drugs mitomycin C, β-lapachone and the benzoquinone ansamycin class of Hsp90 inhibitors including 17-AAG. The role of NQO1 in the bioreductive activation of mitomycin C remains controversial but pre-clinical data strongly suggests a role for NQO1 in the activation of β-lapachone and the benzoquinone ansamycin class of Hsp90 inhibitors. Despite a large volume of preclinical data demonstrating that NQO1 is an important determinant of sensitivity to these antitumor quinones there is little information on whether the clinical response to these agents is influenced by the NQO1*2 polymorphism. The availability of simple assays for the determination of the NQO1*2 polymorphism should facilitate clinical testing of this hypothesis.
Topics: Antineoplastic Agents; Benzoquinones; Drug Resistance, Neoplasm; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Mitomycin; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Neoplasms; Polymorphism, Genetic; Quinones; Rifabutin
PubMed: 22209713
DOI: 10.1016/j.bcp.2011.12.017 -
The Journal of Antimicrobial... Jan 2010The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma...
BACKGROUND
The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration.
METHODS
Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake.
RESULTS
Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54).
CONCLUSIONS
This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.
Topics: Adult; Alkynes; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Body Weight; Cyclopropanes; Female; HIV Infections; Humans; Lopinavir; Male; Middle Aged; Oligopeptides; Plasma; Pyridines; Pyrimidinones; Rifabutin; United Kingdom
PubMed: 19897506
DOI: 10.1093/jac/dkp408 -
Journal of Infection and Public Health Nov 2022The high incidences of COVID-19 cases are believed to be associated with high transmissibility rates, which emphasizes the need for the discovery of evidence-based...
The high incidences of COVID-19 cases are believed to be associated with high transmissibility rates, which emphasizes the need for the discovery of evidence-based antiviral therapies for curing the disease. The rationale of repurposing existing classes of antiviral small molecule therapeutics against SARS-CoV-2 infection has been expected to accelerate the tedious and expensive drug development process. While Remdesivir has been recently approved to be the first treatment option for specific groups of COVID-19 patients, combinatory therapy with potential antiviral drugs may be necessary to enhance the efficacy in different populations. Hence, a comprehensive list of investigational antimicrobial drug compounds such as Favipiravir, Fidaxomicin, Galidesivir, GC376, Ribavirin, Rifabutin, and Umifenovir were computationally evaluated in this study. We performed in silico docking and molecular dynamics simulation on the selected small molecules against RNA-dependent RNA polymerase, which is one of the key target proteins of SARS-CoV-2, using AutoDock and GROMACS. Interestingly, our results revealed that the macrocyclic antibiotic, Fidaxomicin, possesses the highest binding affinity with the lowest energy value of -8.97 kcal/mol binding to the same active sites of RdRp. GC376, Rifabutin, Umifenovir and Remdesivir were identified as the next best compounds. Therefore, the above-mentioned compounds could be considered good leads for further preclinical and clinical experimentations as potentially efficient antiviral inhibitors for combination therapies against SARS-CoV-2.
Topics: Humans; SARS-CoV-2; RNA-Dependent RNA Polymerase; COVID-19; Antiviral Agents; Fidaxomicin; Drug Repositioning; Molecular Docking Simulation; Rifabutin
PubMed: 36240528
DOI: 10.1016/j.jiph.2022.09.007