Rifabutin

Last updated
Rifabutin
Rifabutin structure.svg
Clinical data
Trade names Mycobutin [1]
AHFS/Drugs.com Monograph
MedlinePlus a693009
Pregnancy
category
  • AU:C
Routes of
administration
By mouth (capsules)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 85%
Protein binding 85%
Metabolism liver
Elimination half-life 28 to 62 hours (mean)
Excretion kidney and fecal
Identifiers
  • (9S,12E,14S,15R,16S,17R,18R,19R,20S,
    21S,22E,24Z)-6,16,18,20-tetrahydroxy-1'-
    isobutyl-14-methoxy-7,9,15,17,19,21,25-
    hepta-methyl-spiro[9,4-(epoxypentadeca
    [1,11,13]trienimino)-2H-furo-[2',3':7,8]-naphth
    [1,2-d]imidazol-2,4'-piperidin]-5,10,26-(3H,9H)-
    trione-16-acetate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.133.627 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C46H62N4O11
Molar mass 847.019 g·mol−1
3D model (JSmol)
  • C[C@H]1/C=C\C=C(/C(=O)NC2=C3C(=NC4(N3)CCN(CC4)CC(C)C)C5=C6C(=C(C(=C5C2=O)O)C)O[C@@](C6=O)(O/C=C\[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)\C
  • InChI=1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12+,20-15+,24-14-/t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1 Yes check.svgY
  • Key:ATEBXHFBFRCZMA-VXTBVIBXSA-N Yes check.svgY
   (verify)

Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex. [1] It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. [1] For active tuberculosis it is used with other antimycobacterial medications. [1] For latent tuberculosis it may be used by itself when the exposure was with drug-resistant TB. [1]

Contents

Common side effects include abdominal pain, nausea, rash, headache, and low blood neutrophil levels. [1] Other side effects include muscles pains and uveitis., [1] especially when hitting Bartonella and Babesia colonies in the capillaries of the ciliary body in the eye anterior chamber. While no harms have been found during pregnancy it has not been well studied in this population. [1] Rifabutin is in the rifamycin family of medications. [1] It works by blocking RNA production in bacteria. [2]

Rifabutin was approved for medical use in the United States in 1992. [1] It is on the World Health Organization's List of Essential Medicines. [3]

Medical uses

Rifabutin is now recommended as first-line treatment for tuberculosis (TB), [4] but rifampicin was used more widely because of its cheaper cost. However, due to the expiration of patents, prices are now similar.

Rifabutin is also used in the treatment of Mycobacterium avium complex disease, a bacterial infection most commonly encountered in people with late-stage AIDS. Its has fewer drug interactions than rifampicin, therefore people with HIV/AIDS on HAART are typically prescribed rifabutin instead of rifampicin for the treatment of TB.[ citation needed ]

Rifabutin is well-tolerated in people with HIV-related TB, but new findings suggest that those with low CD4+ cell counts have a higher risk of treatment failure or relapse due to acquired rifamycin resistance. Since patients co-infected with TB and HIV are likely to be treated for TB first, when the CD4+ cell population is depressed at the time TB treatment begins, doctors and patients should be aware of the possibility for rifamycin resistance to develop.[ citation needed ]

Crohn's disease

Rifabutin is being tested in clinical trials for treating Crohn's disease as part of the anti-MAP therapy. In a Phase III study administering sub-therapeutic doses of rifabutin in combination therapy to patients not identified with Mycobacterium aviumparatuberculosis (MAP) infections, it was associated with significant short term benefits. [5] [6]

Others

Rifabutin is also being investigated for the treatment of infections caused by the Gram-negative bacillus Acinetobacter baumannii , which has shown promise in animal studies. [7]

Rifamycins, including rifabutin, are useful in the treatment of Chlamydophila pneumoniae (Cpn) infection.[ citation needed ]

History

Scientists at the Italian drug company Achifar discovered rifabutin in 1975. (Eventually Archifar became part of Farmitalia Carlo Erba, a unit of the conglomerate Montedison which was subsequently bought by Pharmacia) This company's Adria Laboratories subsidiary filed for Food and Drug Administration (FDA) approval of rifabutin under the brand name Mycobutin in the early 1990s and the drug gained FDA approval in December 1992.[ citation needed ]

Rifabutin is primarily bactericidal antibiotic drug used to treat tuberculosis. Its effect on bacteria is based on the DNA-dependent RNA polymerase blocking drug rifamycin S, a semi-synthetic derivative. It is effective, for example, in highly resistant mycobacteria, Gram-positive bacteria (and some are effective against Gram-negative bacteria), but also against Mycobacterium tuberculosis , M. leprae, and M. avium intracellulare .[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Tuberculosis</span> Infectious disease

Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. Infection of other organs can cause a wide range of symptoms.

<span class="mw-page-title-main">Isoniazid</span> Antibiotic for treatment of tuberculosis

Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For latent tuberculosis, it is often used alone. It may also be used for atypical types of mycobacteria, such as M. avium, M. kansasii, and M. xenopi. It is usually taken by mouth, but may be used by injection into muscle.

<span class="mw-page-title-main">Rifamycin</span> Group of antibiotics

The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections.

<span class="mw-page-title-main">Rifampicin</span> Antibiotic medication

Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), Mycobacterium avium complex, leprosy, and Legionnaires' disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.

Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and suspected causative agent in human Crohn's disease and rheumatoid arthritis. The type strain is ATCC 19698.

<span class="mw-page-title-main">Tuberculosis management</span>

Tuberculosis management describes the techniques and procedures utilized for treating tuberculosis (TB).

Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.

<span class="mw-page-title-main">4-Aminosalicylic acid</span> Anti-tuberculosis and anti-inflammatory drug

4-Aminosalicylic acid, also known as para-aminosalicylic acid (PAS) and sold under the brand name Paser among others, is an antibiotic primarily used to treat tuberculosis. Specifically it is used to treat active drug resistant tuberculosis together with other antituberculosis medications. It has also been used as a second line agent to sulfasalazine in people with inflammatory bowel disease such as ulcerative colitis and Crohn's disease. It is typically taken by mouth.

<span class="mw-page-title-main">Amikacin</span> Antibiotic medication

Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of multidrug-resistant tuberculosis. It is used by injection into a vein using an IV or into a muscle.

<i>Mycobacterium avium-intracellulare</i> infection Medical condition

Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex (MAC), which is made of two Mycobacterium species, M. avium and M. intracellulare. This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS, it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.

<span class="mw-page-title-main">Rifapentine</span> Chemical compound

Rifapentine, sold under the brand name Priftin, is an antibiotic used in the treatment of tuberculosis. In active tuberculosis it is used together with other antituberculosis medications. In latent tuberculosis it is typically used with isoniazid. It is taken by mouth.

Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) is when a person is infected with Mycobacterium tuberculosis, but does not have active tuberculosis (TB). Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these people will go on to develop active tuberculosis. This is particularly true, and there is added risk, in particular situations such as medication that suppresses the immune system or advancing age.

The rpoB gene encodes the β subunit of bacterial RNA polymerase and the homologous plastid-encoded RNA polymerase (PEP). It codes for 1342 amino acids in E. coli, making it the second-largest polypeptide in the bacterial cell. It is targeted by the rifamycin family of antibacterials, such as rifampin. Mutations in rpoB that confer resistance to rifamycins do so by altering the protein's drug-binding residues, thereby reducing affinity for these antibiotics.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

<span class="mw-page-title-main">Extensively drug-resistant tuberculosis</span> Tuberculosis that is resistant to the most effective drugs

Extensively drug-resistant tuberculosis (XDR-TB) is a form of tuberculosis caused by bacteria that are resistant to some of the most effective anti-TB drugs. XDR-TB strains have arisen after the mismanagement of individuals with multidrug-resistant TB (MDR-TB).

<span class="mw-page-title-main">Multidrug-resistant tuberculosis</span> Medical condition

Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs): isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).

<span class="mw-page-title-main">Tuberculosis in India</span> Health issue in India

Tuberculosis in India is a major health problem, causing about 220,000 deaths every year. In 2020, the Indian government made statements to eliminate tuberculosis from the country by 2025 through its National TB Elimination Program. Interventions in this program include major investment in health care, providing supplemental nutrition credit through the Nikshay Poshan Yojana, organizing a national epidemiological survey for tuberculosis, and organizing a national campaign to tie together the Indian government and private health infrastructure for the goal of eliminating the disease.

The co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major global health challenges in the present time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common contagious infection in HIV-Immunocompromised patients leading to death. These diseases act in combination as HIV drives a decline in immunity while tuberculosis progresses due to defective immune status. This condition becomes more severe in case of multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Tuberculosis can occur at any stage of HIV infection. The risk and severity of tuberculosis increases soon after infection with HIV. A study on gold miners of South Africa revealed that the risk of TB was doubled during the first year after HIV seroconversion. Although tuberculosis can be a relatively early manifestation of HIV infection, it is important to note that the risk of tuberculosis progresses as the CD4 cell count decreases along with the progression of HIV infection. The risk of TB generally remains high in HIV-infected patients, remaining above the background risk of the general population even with effective immune reconstitution and high CD4 cell counts with antiretroviral therapy.

<span class="mw-page-title-main">Robert T. Schooley</span> American infectious disease physician

Robert "Chip" T. Schooley is an American infectious disease physician, who is the Vice Chair of Academic Affairs, Senior Director of International Initiatives, and Co-Director at the Center for Innovative Phage Applications and Therapeutics (IPATH), at the University of California San Diego School of Medicine. He is an expert in HIV and hepatitis C (HCV) infection and treatment, and in 2016, was the first physician to treat a patient in the United States with intravenous bacteriophage therapy for a systemic bacterial infection.

References

  1. 1 2 3 4 5 6 7 8 9 10 "Rifabutin". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  2. Rockwood N, Cerrone M, Barber M, Hill AM, Pozniak AL (July 2019). "Global access of rifabutin for the treatment of tuberculosis - why should we prioritize this?". Journal of the International AIDS Society. 22 (7): e25333. doi:10.1002/jia2.25333. PMC   6637439 . PMID   31318176. Rifabutin is a rifamycin, which like rifampicin, works via inhibition of DNA‐dependent RNA synthesis in prokaryotes.
  3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008 (WHO/HTM/TB/2008.402). Geneva, Switzerland: World Health Organization. 2008. p. ix. ISBN   978-92-4-154758-1. Archived from the original on 2008-10-18.
  5. Selby W, Pavli P, Crotty B, Florin T, Radford-Smith G, Gibson P, et al. (Antibiotics in Crohn's Disease Study Group) (June 2007). "Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease". Gastroenterology. 132 (7): 2313–2319. doi:10.1053/j.gastro.2007.03.031. PMID   17570206.
  6. Kuenstner JT (November 2007). "The Australian antibiotic trial in Crohn's disease: alternative conclusions from the same study". Gastroenterology. 133 (5): 1742–1743. doi: 10.1053/j.gastro.2007.09.012 . PMID   17983824.
  7. Luna B, Trebosc V, Lee B, Bakowski M, Ulhaq A, Yan J, et al. (September 2020). "A nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii". Nature Microbiology. 5 (9): 1134–1143. doi:10.1038/s41564-020-0737-6. PMC   7483275 . PMID   32514072. S2CID   219543106.