HWN Suggests

Rifamycins: do not throw the baby out with the bathwater. Is rifampicin still an effective anti-tuberculosis drug?

It is apparent that the benefits of using rifampicin for TB treatment outweigh its pitfalls, although there is an increase in drug-resistant TB strains. It safe to say that without this remarkable natural product, the fight against TB would have been much more arduous in the last 50 years, and rifampicin still serves as an effective tool to tackle the TB pandemic. As it stands, this active pharmaceutical ingredient remains a key element of first-line TB drug regimens and appears to have more aces up its sleeve. In fact, adjustments of the rifampicin dose regimen or chemical alterations of its structural framework might allow this drug, or novel derivatives, to be successfully employed in TB…

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Featured

 A Simple Regimen Can Prevent TB. Why Aren’t More People on It?

Two antibiotics, taken for a month, can stop a leading killer. But “when it’s for TB, people just sort of shrug.” For decades, the standard course has been an antibiotic called isoniazid that kills the bacteria causing TB only when they are replicating. The drug must be taken daily for nine months, in the hope of catching the bacteria as they multiply, and it can cause numbness, nausea and fever. Isoniazid also can cause liver toxicity, so people taking it are advised not to drink alcohol for the entire nine months.

 Rifamycin-Resisting Trick Discovered in Bacteria

“We find the genes associated with this resistance are widespread in environmental bacteria and some human pathogens—luckily not the ones that cause tuberculosis, but some related ones,” said Wright.

Articles of Interest

Comparison of Rifamycins for Efficacy Against Mycobacterium avium Complex...

Rifamycins are integral part of the combination regimen for treatment of pulmonary Mycobacterium avium-complex [MAC] infection, but different practitioners prefer different rifamycins. The objective of the study was to compare microbial kill and resistance emergence of rifamycins using principles of pharmacokinetics/pharmacodynamics.

High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis

There is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens. HDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR.

How Bad Drugs Turn Treatable Diseases Deadly

Muhammad Zaman learned at an early age that one did not shop for medicine at the convenient neighborhood pharmacy. His most recent discovery has startling implications for our understanding of drug resistance: a low-quality version of rifampin, a broad spectrum antibiotic typically used as the first line of defense to treat tuberculosis, can greatly contribute to the development of drug-resistant infections. “There had not been a definitive study showing that lack of [antibiotic] quality leads to resistance,” says Zaman, who is also a Howard Hughes Medical Institute Professor of Biomedical Engineering and International Health. “Now we are sure that it does, and it does with TB, a global problem that has become stubbornly hard to resolve.”

Rifampin vs. rifapentine: what is the preferred rifamycin for tuberculosis?

For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care.

Rifamycin antibiotics and the mechanisms of their failure

Rifamycins are a class of antibiotics that were first discovered in 1957 and are known for their use in treating tuberculosis (TB). Rifamycins exhibit bactericidal activity against many Gram-positive and Gram-negative bacteria by inhibiting RNA polymerase (RNAP); however, resistance is prevalent and the mechanisms range from primary target modification and antibiotic inactivation to cytoplasmic exclusion.

Rifamycins, Alone and in Combination

Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram-positive prosthetic joint and valve infections, in which biofilms are prominent. Rifabutin has use for AIDS patients in treating mycobacterial infections TB and Mycobacterium avium complex (MAC), having fewer drug–drug interactions that interfere with AIDS medications. Rifabutin is occasionally used in combination to eradicate Helicobacter pylori (peptic ulcer disease). Rifapentine has yet to fulfill its potential in reducing time of treatment for TB.

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UpToDate

The rifamycins include rifampin, rifapentine, and rifabutin. Of these, rifampin is most commonly used, either as first-line therapy (in combination with other agents) for treatment of mycobacterial disease (including tuberculosis) or for select invasive staphylococcal infections (as part of combination therapy).