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Rifampin

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1. The combination rifampin-nitazoxanide, but not rifampin-isoniazid-pyrazinamide-ethambutol, kills dormant <i>Mycobacterium tuberculosis</i> in hypoxia at neutral pH. (PubMed)

The combination rifampin-nitazoxanide, but not rifampin-isoniazid-pyrazinamide-ethambutol, kills dormant Mycobacterium tuberculosis in hypoxia at neutral pH. The activities of rifampin, nitazoxanide, PA-824, sutezolid, were tested against dormant Mycobacterium tuberculosis under conditions mimicking caseous granulomas (hypoxia at pH 7.3), in comparison with the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), used for human therapy. Mycobacterial viability was monitored (...) by CFU and regrowth in MGIT 960 tubes. As shown by lack of regrowth in MGIT, rifampin-nitazoxanide containing combinations, but not R-I-Z-E, killed dormant cells in 28-35 days. These observations might be important in designing new tuberculosis therapies.Copyright © 2019 American Society for Microbiology.

2019 Antimicrobial Agents and Chemotherapy

2. Treatment outcomes of rifampin-sparing treatment in patients with pulmonary tuberculosis with rifampin-mono-resistance or rifampin adverse events: A retrospective cohort analysis. (PubMed)

Treatment outcomes of rifampin-sparing treatment in patients with pulmonary tuberculosis with rifampin-mono-resistance or rifampin adverse events: A retrospective cohort analysis. Rifampin (RIF) mono-resistant tuberculosis (RMR-TB) is a rare disease. Current guidelines recommend that RMR-TB be treated as multidrug-resistant TB (MDR-TB) but the evidence is scarce.We conducted a retrospective cohort study on pulmonary TB patients to investigate the characteristics and outcomes of RMR-TB (...) . The characteristics of RMR-TB were compared with those with adverse events to rifampin (RAE-TB).Forty-four RMR-TB and 29 RAE-TB patients were enrolled. RMR-TB patients showed more alcohol use, prior history of TB, and radiologically severe disease, while RAE-TB patients were older and had more comorbidities and combined extrapulmonary TB. A fluoroquinolone (FQ) was the drug most commonly added (70.5%, RMR-TB; 82.8%, RAE-TB). Median treatment duration was 453 days in RMR-TB and 371 days in RAE-TB (p = 0.001

2017 Respiratory medicine

3. Characterization of rifampin-resistant Staphylococcus aureus nasal carriage in patients receiving rifampin-containing regimens for tuberculosis (PubMed)

Characterization of rifampin-resistant Staphylococcus aureus nasal carriage in patients receiving rifampin-containing regimens for tuberculosis This study investigated molecular characteristics of rifampin (RIF)-resistant (RIF-R) Staphylococcus aureus isolates recovered from patients receiving RIF-containing regimens for tuberculosis (TB).Patients with TB who received RIF-containing regimens from November 2009 to May 2011 at a medical center were enrolled. Nasal swabs for S. aureus culture were

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2018 Infection and drug resistance

4. Topical Rifampin Powder for Orthopaedic Trauma Part II: Topical rifampin allows for spontaneous bone healing in sterile and contaminated wounds. (PubMed)

Topical Rifampin Powder for Orthopaedic Trauma Part II: Topical rifampin allows for spontaneous bone healing in sterile and contaminated wounds. Infectious complications can reduce fracture healing rate. Broad spectrum antibiotics are commonly administered to prevent and treat musculoskeletal infections. Local antibiotics are applied to the wound site to increase therapeutic concentrations without increasing systemic toxicity, however, may hinder local tissue recovery. Rifampin has been shown (...) to eradicate mature Staphylococcal biofilms and its use proven for treating musculoskeletal infections. In this study, a spontaneously healing defect model in a rat was used to investigate the impact rifampin powder has on endogenous bone healing in both a sterile and contaminated wound. No significant differences were identified in bone volume fraction via microcomputed tomography, radiological scoring, or histology between an empty defect and animals that received vancomycin or rifampin powder

2018 Journal of Orthopaedic Research

5. Topical Rifampin Powder for Orthopaedic Trauma Part I: Rifampin powder reduces recalcitrant infection in a delayed treatment musculoskeletal trauma model. (PubMed)

Topical Rifampin Powder for Orthopaedic Trauma Part I: Rifampin powder reduces recalcitrant infection in a delayed treatment musculoskeletal trauma model. Open fractures become infected despite meticulous debridement and care. Locally applied antibiotics, commonly embedded in polymethylmethacrylate, deliver high doses of drug directly to the fracture site. Direct application of antibiotic powder, which is being applied prophylactically in spine surgery, is a recent interest in the trauma sector (...) , where bacterial biofilms are more prevalent. Traditional antibiotics, such as vancomycin, are poor performers against bacterial biofilms thus are ineffective in delayed treatment. Rifampin is an effective eradicator of Staphylococcal biofilms. Here, a rat model of musculoskeletal trauma was used to evaluate the utility of locally applied rifampin powder for reducing established orthopedic Staphylococcal infections in a delayed treatment scenario that previously indicated the limited use of local

2018 Journal of Orthopaedic Research

6. A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis. (PubMed)

A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis. Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011.We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 (...) -regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively.In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen

2019 NEJM

7. Safety and Side Effects of Rifampin versus Isoniazid in Children. (PubMed)

Safety and Side Effects of Rifampin versus Isoniazid in Children. The treatment of latent infection with Mycobacterium tuberculosis is important in children because of their vulnerability to life-threatening forms of tuberculosis disease. The current standard treatment - 9 months of isoniazid - has been associated with poor adherence and toxic effects, which have hampered the effectiveness of the drug. In adults, treatment with 4 months of rifampin has been shown to be safer and to have higher (...) completion rates than 9 months of isoniazid.In this multicenter, open-label trial, we randomly assigned 844 children (<18 years of age) with latent M. tuberculosis infection to receive either 4 months of rifampin or 9 months of isoniazid. The primary outcome was adverse events of grade 1 to 5 that resulted in the permanent discontinuation of a trial drug. Secondary outcomes were treatment adherence, side-effect profile, and efficacy. Independent review panels whose members were unaware of trial-group

2018 NEJM

8. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. (PubMed)

Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects.In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid (...) for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels.Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person

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2018 NEJM

9. Rifampin-Based Combination Therapy is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy. (PubMed)

Rifampin-Based Combination Therapy is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy. Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign (...) -body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated

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2016 Antimicrobial Agents and Chemotherapy

10. Structural basis of rifampin inactivation by rifampin phosphotransferase (PubMed)

Structural basis of rifampin inactivation by rifampin phosphotransferase Rifampin (RIF) is a first-line drug used for the treatment of tuberculosis and other bacterial infections. Various RIF resistance mechanisms have been reported, and recently an RIF-inactivation enzyme, RIF phosphotransferase (RPH), was reported to phosphorylate RIF at its C21 hydroxyl at the cost of ATP. However, the underlying molecular mechanism remained unknown. Here, we solve the structures of RPH from Listeria

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2016 Proceedings of the National Academy of Sciences of the United States of America

11. Rifampin-warfarin interaction in a mitral valve replacement patient receiving rifampin for infective endocarditis: a case report (PubMed)

Rifampin-warfarin interaction in a mitral valve replacement patient receiving rifampin for infective endocarditis: a case report Warfarin therapy is associated with many drug interactions that may cause a significant alteration in its anticoagulant effect. Rifampin is a widely used antimicrobial that has major interactions with several medications including warfarin due to its strong P-glycoprotein and liver enzyme inducer activity especially on CYP2C9, CYP3A4, CYP1A2 and CYP2C19.We report (...) a case of a 34-year-old Srilankan female chronically treated with warfarin for her mitral valve replacement. The patient developed infective endocarditis and was started on a 6-week treatment with rifampin along with other antibiotics. Warfarin dose was increased from 52.5 to 210 mg/week over the course of the rifampin therapy, however, the INR remained subtherapeutic throughout the whole period and reached 2.4 by the end of rifampin therapy.Anticoagulation management was challenging in the period

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2016 SpringerPlus

12. A randomized, comparative study of dual therapy (doxycycline-rifampin) versus triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis. (PubMed)

A randomized, comparative study of dual therapy (doxycycline-rifampin) versus triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis. The aim of this study was to compare both the efficacy and safety profile of the WHO-recommended, dual therapy (doxycycline-rifampin) to a quinolone-based, triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis.We studied 107 consecutive, naïve patients with acute/subacute brucellosis (...) admitted to Assiut University Hospital. Patients were randomly allocated to receive the dual therapy of doxycycline-rifampin (group-A) or to receive the triple therapy of doxycycline-rifampin-levofloxacin (group-B). Acute/subacute brucellosis was diagnosed based on the presence of: (1) contact with animals or fresh animal products, (2) suggestive clinical manifestations of less than one-year duration, and (3) positive antibody titer (1:160) by standard tube agglutination test.There was no significant

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2016 The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases

13. Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance. (PubMed)

Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance. The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible (...) for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not. Their failure to develop tolerance may be explained by their harboring of a loss-of-function mutation in the Rv1258c efflux pump that is linked to macrophage-induced rifampicin tolerance.

2019 Journal of Infectious Diseases

14. Healthcare Provider Discrimination toward Pregnant Women with Rifampin-Resistant Tuberculosis. (PubMed)

Healthcare Provider Discrimination toward Pregnant Women with Rifampin-Resistant Tuberculosis. Little is known about the treatment experiences of pregnant women with rifampin-resistant tuberculosis. We conducted qualitative interviews with 10 women who had this condition; 9 reported facing discrimination from healthcare providers. Our findings underscore an urgent need to ensure a human-rights-based, patient-centered approach for women with rifampin-resistant tuberculosis who are pregnant.

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2019 Emerging Infectious Diseases

15. Assessment of the potential for inducing resistance in multidrug resistant organisms from exposure to minocycline, rifampin and chlorhexidine used to treat intravascular devices. (PubMed)

Assessment of the potential for inducing resistance in multidrug resistant organisms from exposure to minocycline, rifampin and chlorhexidine used to treat intravascular devices. To assess the potential for induction of antimicrobial resistance following repeated sub-inhibitory exposures to the combination Minocycline (M), Rifampin (R), and Chlorhexidine (CH), a total of 29 clinical microbial pathogenic isolates were repeatedly exposed to sub-inhibitory concentrations of M, R and CH for 20

2019 Antimicrobial Agents and Chemotherapy

16. Emergence and selection of isoniazid and rifampin resistance in tuberculosis granulomas. (PubMed)

Emergence and selection of isoniazid and rifampin resistance in tuberculosis granulomas. Drug resistant tuberculosis is increasing world-wide. Resistance against isoniazid (INH), rifampicin (RIF), or both (multi-drug resistant TB, MDR-TB) is of particular concern, since INH and RIF form part of the standard regimen for TB disease. While it is known that suboptimal treatment can lead to resistance, it remains unclear how host immune responses and antibiotic dynamics within granulomas (sites

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2018 PLoS ONE

17. Mycobactericidal activity of bedaquiline plus rifabutin or rifampin in ex vivo whole blood cultures of healthy volunteers: A randomized controlled trial. (PubMed)

Mycobactericidal activity of bedaquiline plus rifabutin or rifampin in ex vivo whole blood cultures of healthy volunteers: A randomized controlled trial. Bedaquiline, an antimycobacterial agent approved for drug-resistant tuberculosis, is metabolized by CYP3A4, an hepatic enzyme strongly induced by rifampin, an essential part of drug-sensitive tuberculosis treatment. We examined the pharmacokinetic interactions of bedaquiline plus either rifampin or rifabutin in 33 healthy volunteers. This sub (...) -study of that trial examined the mycobactericidal activity of these drugs against intracellular Mycobacterium tuberculosis using ex vivo whole blood culture.Subjects were randomly assigned to receive two single 400 mg doses of bedaquiline, alone, and, after a 4 week washout period, in combination with steady-state daily dosing of either rifabutin 300 mg or rifampin 600 mg. Blood samples were collected prior to dosing and at multiple time points subsequently, to measure plasma drug concentrations

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2018 PLoS ONE

18. Feasibility of Identifying Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease. (PubMed)

Feasibility of Identifying Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease. We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial.We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in eight high-TB-burden countries. HHCs underwent symptom screening, chest radiography (CXR), sputum TB

2019 Clinical Infectious Diseases

19. Rifampin-Resistant Tuberculosis In The United States, 1998-2014. (PubMed)

Rifampin-Resistant Tuberculosis In The United States, 1998-2014. Monoresistance to rifamycins necessitates longer and more toxic regimens for tuberculosis (TB). We examined characteristics and mortality associated with rifampin-monoresistant (RMR) TB in the United States.We analyzed Mycobacterium tuberculosis culture-positive cases reported to the National TB Surveillance System (excluding California because HIV infection was not reported to CDC during 2005-2010) between 1998 and 2014. We (...) defined: (1) RMR TB found on initial drug susceptibility testing (DST), and (2) possible acquired rifampin-resistant (ARR) TB. We assessed temporal trends in RMR TB. For both classifications of rifampin resistance, we calculated adjusted risk ratios (adjRR) and 95% confidence intervals (CI) for social and clinical characteristics associated with mortality when compared to drug-susceptible TB in multivariable models using backwards selection.Of 180,329 TB cases, 126,431 (70%) cases were eligible

2019 Clinical Infectious Diseases

20. Rifampin Pharmacokinetics and Safety in Preterm and Term Infants. (PubMed)

Rifampin Pharmacokinetics and Safety in Preterm and Term Infants. Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23-41), and PNA was 10 days (0-84). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data (...) from all 27 infants. We analyzed the data using a population PK approach. Rifampin PK was best characterized by a one-compartment model; drug clearance increased with increasing size (body weight) and maturation (PNA). There were no adverse events related to rifampin. Simulated weight and PNA-based intravenous dosing regimens administered once daily (<14 days PNA, 8 mg/kg; ≥14 days PNA, 15 mg/kg) in infants resulted in comparable exposures to adults receiving therapeutic doses of rifampin against

2019 Antimicrobial Agents and Chemotherapy

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