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Canadian Medical Association Journal Apr 1972Rifampin is a potent antituberculous drug. In the treatment of drug-resistant tuberculosis it is highly effective provided it is given in combination with other drugs to... (Review)
Review
Rifampin is a potent antituberculous drug. In the treatment of drug-resistant tuberculosis it is highly effective provided it is given in combination with other drugs to which the patient's organisms are sensitive. Rifampin and ethambutol is a particularly powerful combination and will achieve almost 100% sputum conversion. It seems likely that rifampin will replace streptomycin, and ethambutol will replace PAS in first-treatment cases. Optimum first-line treatment will thus consist of rifampin, INH and ethambutol, with the probability of almost 100% success and the possibility also that the total duration of treatment may be considerably reduced. Rifampin is well tolerated but it may give rise to liver dysfunction and thrombocytopenia in a small proportion of patients. Patients treated with rifampin must be kept under close supervision because of the risk of side effects and, more important, because irregular treatment may lead to the development of rifampin-resistant organisms.
Topics: Adult; Aged; Animals; Drug Combinations; Ethambutol; Female; Humans; Isoniazid; Jaundice; Male; Mice; Middle Aged; Mycobacterium tuberculosis; Pregnancy; Rifampin; Thrombocytopenia; Tuberculosis, Pulmonary
PubMed: 4622757
DOI: No ID Found -
Journal of Vascular Surgery Sep 2019
Topics: Rifampin; Vascular Surgical Procedures
PubMed: 31445640
DOI: 10.1016/j.jvs.2019.05.007 -
Journal of Pain and Symptom Management Dec 2015Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is... (Review)
Review
Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles ([email protected]).
Topics: Antibiotics, Antitubercular; Drug Interactions; Humans; Internet; Palliative Care; Rifampin
PubMed: 26432572
DOI: 10.1016/j.jpainsymman.2015.09.004 -
Antimicrobial Agents and Chemotherapy Jun 2019Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety... (Clinical Trial)
Clinical Trial
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 of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). 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 staphylococcal infections and TB. (This study has been registered at ClinicalTrials.gov under identifier NCT01728363.).
Topics: Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Prospective Studies; Rifampin; Staphylococcal Infections; Tuberculosis
PubMed: 30910891
DOI: 10.1128/AAC.00284-19 -
The New England Journal of Medicine Mar 2019
Topics: HIV; Humans; Isoniazid; Rifampin; Tuberculosis
PubMed: 30865803
DOI: 10.1056/NEJMe1901656 -
International Journal of Molecular... Nov 2023has emerged as a critical human pathogen, and a number of isolated reports have described the successful treatment of infections with vancomycin, a drug that is...
has emerged as a critical human pathogen, and a number of isolated reports have described the successful treatment of infections with vancomycin, a drug that is typically used to target Gram-positive bacteria. This study employed in vitro broth microdilution checkerboard and time-kill assays, as well as in vivo zebrafish animal models to evaluate the individual and combination antimicrobial effects of vancomycin and rifampin against . The minimum inhibitory concentration ranges of vancomycin and rifampin against 167 isolates of were 16-256 mg/L and 0.06-128 mg/L, respectively. The checkerboard assay results revealed a synergistic effect between vancomycin and rifampin in 16.8% (28/167) of the isolates. Time-kill assays were implemented for 66 isolates, and the two-drug combination had a synergistic interaction in 57 (86.4%) isolates. In vivo zebrafish studies revealed that treatment with vancomycin monotherapy, rifampin monotherapy, or vancomycin-rifampin combination therapy yielded a higher survival rate than the control group treatment with 0.9% saline. The results of this study support the use of vancomycin to treat infections.
Topics: Animals; Humans; Vancomycin; Rifampin; Anti-Bacterial Agents; Zebrafish; Microbial Sensitivity Tests
PubMed: 38069334
DOI: 10.3390/ijms242317012 -
Microbiology Spectrum Dec 2022The emergence of bacterial drug resistance poses a severe threat to global public health. In particular, antimicrobial-resistant pathogens lead to a high rate of...
The emergence of bacterial drug resistance poses a severe threat to global public health. In particular, antimicrobial-resistant pathogens lead to a high rate of treatment failure and significantly increase mortality. Repurposing FDA-approved compounds to sensitize superbugs to conventional antibiotics provides a promising strategy to alleviate such crises. Pixantrone (PIX) has been approved for treating aggressive B-cell non-Hodgkin's lymphoma. By high-throughput drug screening, we profiled the synergistic activity between PIX and rifampin (RFP) against Gram-negative extensively drug-resistant isolates by checkerboard assay. Mechanistic studies demonstrated that PIX impacted the flagellum assembly, induced irreversible intracellular reactive oxygen species accumulation and disrupted proton motive force. In addition, the combination of PIX with RFP possesses effective antimicrobial activity against multidrug-resistant strains without detected toxicity. Collectively, these results reveal the potential of PIX in combination with RFP as a therapy option for refractory infections caused by Gram-negative pathogens. Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health. Drug repurposing, the process of finding new uses for existing drugs, provide a promising pathway to solve antimicrobial resistance. Compared to the development of novel antibiotics, this strategy leverages well-characterized pharmacology and toxicology of known drugs and is more cost-effective.
Topics: Humans; Rifampin; Anti-Bacterial Agents; Isoquinolines; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Gram-Negative Bacteria
PubMed: 36318018
DOI: 10.1128/spectrum.02114-22 -
PloS One 2022Traditionally, single critical concentrations of drugs are utilized for Mycobacterium tuberculosis (Mtb) drug susceptibility testing (DST); however, the level of drug...
INTRODUCTION
Traditionally, single critical concentrations of drugs are utilized for Mycobacterium tuberculosis (Mtb) drug susceptibility testing (DST); however, the level of drug resistance can impact treatment choices and outcomes. Mutations at the katG gene are the major genetic mutations in multidrug resistant (MDR) Mtb and usually associated with high level resistance. We assessed the minimum inhibitory concentrations (MICs) of MDR or rifampin resistant (RR) and isoniazid (INH) resistant Mtb isolates to determine the quantification of drug resistance among key anti-tuberculosis drugs.
METHODS
The study was conducted on stored Mtb isolates collected as part of a national drug resistance survey in Ethiopia. MIC values were determined using Sensititre™ MYCOTB plates. A line probe assay (MTBDRplus) was also performed to identify genetic determinants of resistance for all isolates.
RESULTS
MIC testing was performed on 74 Mtb isolates including 46 MDR, 2 RR and 26 INH phenotypically resistant isolates as determined by the Löwenstein Jensen (LJ) method. Four (15%) INH resistant Mtb isolates were detected as borderline rifampin resistance (MIC = 1 μg/ml) using MYCOTB MIC plates and no rifampin resistance mutations were detected by LPA. Among the 48 MDR/RR TB cases, 9 (19%) were rifabutin susceptible (MIC was between ≤0.25 and 0.5μg/ml). Additionally, the MIC for isoniazid was between 2-4 μg/ml (moderate resistance) for 58% of MDR TB isolates and 95.6% (n = 25) of the isolates had mutations at the katG gene.
CONCLUSION
Our findings suggest a role for rifabutin treatment in a subset of RR TB patients, thus potentially preserving an important drug class. The high proportion of moderate level INH resistant among MDR Mtb isolates indicates the potential benefit of high dose isoniazid treatment in a high proportion of katG gene harboring MDR Mtb isolates.
Topics: Ethiopia; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifabutin; Rifampin; Tuberculosis, Multidrug-Resistant
PubMed: 36099255
DOI: 10.1371/journal.pone.0274426 -
Scientific Reports Dec 2022Tuberculous spondylitis often develops catastrophic bone destruction with uncontrolled inflammation. Because anti-tuberculous drugs do not have a role in bone formation,...
Tuberculous spondylitis often develops catastrophic bone destruction with uncontrolled inflammation. Because anti-tuberculous drugs do not have a role in bone formation, a combination drug therapy with a bone anabolic agent could help in fracture prevention and promote bone reconstruction. This study aimed to investigate the influence of teriparatide on the effect of anti-tuberculous drugs in tuberculous spondylitis treatment. We used the virulent Mycobacterium tuberculosis (Mtb) H37Rv strain. First, we investigated the interaction between teriparatide and anti-tuberculosis drugs (isoniazid and rifampin) by measuring the minimal inhibitory concentration (MIC) against H37Rv. Second, we evaluated the therapeutic effect of anti-tuberculosis drugs and teriparatide on our previously developed in vitro tuberculous spondylitis model of an Mtb-infected MG-63 osteoblastic cell line using acid-fast bacilli staining and colony-forming unit counts. Selected chemokines (interleukin [IL]-8, interferon γ-induced protein 10 kDa [IP-10], monocyte chemoattractant protein [MCP]-1, and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]) and osteoblast proliferation (alkaline phosphatase [ALP] and alizarin red S [ARS] staining) were measured. Teriparatide did not affect the MIC of isoniazid and rifampin. In the Mtb-infected MG-63 spondylitis model, isoniazid and rifampin treatment significantly reduced Mtb growth, and cotreatment with teriparatide did not change the anti-tuberculosis effect of isoniazid (INH) and rifampin (RFP). IP-10 and RANTES levels were significantly increased by Mtb infection, whereas teriparatide did not affect all chemokine levels as inflammatory markers. ALP and ARS staining indicated that teriparatide promoted osteoblastic function even with Mtb infection. Cotreatment with teriparatide and the anti-tuberculosis drugs activated bone formation (ALP-positive area increased by 705%, P = 0.0031). Teriparatide was effective against Mtb-infected MG63 cells without the anti-tuberculosis drugs (ARS-positive area increased by 326%, P = 0.0037). Teriparatide had no effect on the efficacy of anti-tuberculosis drugs and no adverse effect on the activity of Mtb infection in osteoblasts. Furthermore, regulation of representative osteoblastic inflammatory chemokines was not changed by teriparatide treatment. In the in vitro Mtb-infected MG-63 cell model of tuberculous spondylitis, cotreatment with the anti-tuberculosis drugs and teriparatide increased osteoblastic function.
Topics: Humans; Isoniazid; Rifampin; Teriparatide; Chemokine CXCL10; Mycobacterium tuberculosis; Antitubercular Agents; Tuberculosis, Spinal
PubMed: 36522387
DOI: 10.1038/s41598-022-25174-6 -
Science Translational Medicine Dec 2021is a major human pathogen causing serious implant–associated infections. Combination treatment with rifampin (10 to 15 mg/kg per day), which has dose-dependent...
is a major human pathogen causing serious implant–associated infections. Combination treatment with rifampin (10 to 15 mg/kg per day), which has dose-dependent activity, is recommended to treat orthopedic implant–associated infections. Rifampin, however, has limited bone penetration. Here, dynamic C-rifampin positron emission tomography (PET) performed in prospectively enrolled patients with confirmed bone infection ( = 3) or without orthopedic infection ( = 12) demonstrated bone/plasma area under the concentration-time curve ratio of 0.14 (interquartile range, 0.09 to 0.19), exposures lower than previously thought. PET-based pharmacokinetic modeling predicted rifampin concentration-time profiles in bone and facilitated studies in a mouse model of orthopedic implant infection. Administration of high-dose rifampin (human equipotent to 35 mg/kg per day) substantially increased bone concentrations (2 mg/liter versus <0.2 mg/liter with standard dosing) in mice and achieved higher bacterial killing and biofilm disruption. Treatment for 4 weeks with high-dose rifampin and vancomycin was noninferior to the recommended 6-week treatment of standard-dose rifampin with vancomycin in mice (risk difference, −6.7% favoring high-dose rifampin regimen). High-dose rifampin treatment ameliorated antimicrobial resistance (0% versus 38%; = 0.04) and mitigated adverse bone remodeling ( < 0.01). Last, whole-genome sequencing demonstrated that administration of high-dose rifampin in mice reduced selection of bacterial mutations conferring rifampin resistance () and mutations in genes potentially linked to persistence. These data suggest that administration of high-dose rifampin is necessary to achieve optimal bone concentrations, which could shorten and improve treatments for orthopedic implant infections.
Topics: Animals; Anti-Bacterial Agents; Humans; Mice; Microbial Sensitivity Tests; Positron-Emission Tomography; Rifampin; Staphylococcal Infections; Staphylococcus aureus
PubMed: 34851697
DOI: 10.1126/scitranslmed.abl6851